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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 1150. Отображено 100.
18-04-2013 дата публикации

Peptides or Antibodies Which Bind to Melanoma Inhibitory Activity (MIA) Protein

Номер: US20130095122A1
Автор: Bosserhoff Anja Katrin, König Burkhard, Riechers Alexander, SCHMIDT Jennifer
Принадлежит:

The present invention relates to peptides and antibodies which bind to melanoma inhibitory activity protein and the uses of such peptides and antibodies. The invention also relates to nucleic acids coding for such peptides or antibodies. The invention also relates to pharmaceutical compositions comprising such peptides or antibodies or such nucleic acids. The present invention also relates to small molecule compounds which bind to melanoma inhibitory activity protein and to uses of such small molecule compounds. Moreover, the present invention also relates to a method of preventing dimerization and/or aggregation of melanoma inhibitory activity (MIA) protein. The invention is based on the identification of the relevant sites of interaction of the MIA protein with the inhibitory peptides/antibodies. Considering the amino acid sequence of this protein deprived from the signalling peptide, the residues involved in the interaction are selected from: A7, K53, G54, R55, R57, L58, F59, V64, Y69, R85, D87, K91, and more preferably C17, S18, Y47, G61, G66, D67, L76, W102, D103, C106. 122-. (canceled)23. A peptide or antibody that binds to melanoma inhibitory activity (MIA) protein and prevents dimerization and/or aggregation thereof , which peptide is not SEQ ID NO:46 or 47 , wherein binding of said peptide to MIA protein occurs at a surface of said MIA protein formed by at least three amino acid residues of said MIA protein selected from cysteine 17 , serine 18 , tyrosine 47 , glycine 61 , glycine 66 , aspartate 67 , leucine 76 , tryptophan 102 , aspartate 103 , cysteine 106 , valine 64 , tyrosine 69 , aspartate 87 , lysine 91 , glycine 54 , leucine 58 , phenylalanine 59 , alanine 7 , lysine 53 , arginine 55 , arginine 57 , arginine 85 , and lysine 94 , preferably cysteine 17 , serine 18 , tyrosine 47 , glycine 61 , glycine 66 , aspartate 67 , leucine 76 , tryptophan 102 , aspartate 103 , cysteine 106 , alanine 7 , lysine 53 , arginine 55 , arginine 57 , arginine 85 and ...

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Номер записи: 1
25-04-2013 дата публикации

INHIBITORS OF THE TRYPSIN-LIKE SITE OF THE PROTEASOME AND METHODS OF USE THEREOF

Номер: US20130102527A1
Автор: Filippov Dmitry V., Kisselev Alexei F., Overkleeft Herman
Принадлежит:

The present invention is an inhibitor of the trypsin-like β2/β2i sites of the proteasome. The inhibitor is characterized as being a peptide-based epoxyketone or vinyl sulfone that contains an arginine or 4-aminomethylene-L-phenylalanine at the C-terminus (i.e., at the P1 position). Methods for using the inhibitor to inhibit the activity of the β2/β2i site of a proteasome and treat a proteasome-mediated disease or condition are also described. 1. A peptide-based inhibitor of the proteasome β2/β2i site comprising the structure:{'br': None, '(Y)-(X4)-X3-X2-X1 (SEQ ID NO:2),'}wherein X1 is an Arg or Phe residue or an aminosubstituted phenylalanine derivative wherein said residue or derivative comprises a carboxy-terminal epoxyketone or vinyl sulfone warhead; X2 is Leu or Ser; X3 is Leu, Val, Ser, Arg, His, Lys, Phe or an aminosubstituted phenylalanine derivative; X4 is present or absent and when present is Phe; and Y is present or absent and when present is a capping group.2. The peptide-based inhibitor of claim 1 , wherein the capping group is a label.3. The peptide-based inhibitor of claim 2 , wherein the label comprises a 4 claim 2 ,4-difluoro-4-bora-3a claim 2 ,4a-diaza-s-indacene fluorophore claim 2 , a fluoroscein claim 2 , a rhodamine dye or biotin.4. A pharmaceutical composition comprising the peptide-based inhibitor of and a pharmaceutically acceptable carrier.5. The pharmaceutical composition of claim 4 , further comprising an inhibitor of the proteasome β5/β5i site.6. A method for inhibiting the activity of the β2/β2i site of a proteasome comprising contacting a proteasome with a peptide-based inhibitor of so that activity of the proteasome β2/β2i site is inhibited.7. A method for treating cancer claim 4 , organ graft rejection claim 4 , an auto-immune disease claim 4 , parasitic disease or inflammatory condition comprising administering to a subject in need of treatment an effective amount of the pharmaceutical composition of thereby treating the subject's ...

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Номер записи: 2
29-08-2013 дата публикации

IBAT INHIBITORS FOR THE TREATMENT OF LIVER DISEASES

Номер: US20130225511A1
Автор: Gillberg Per-Göran, Graffner Hans, Starke Ingemar
Принадлежит:

The present invention regards specific IBAT inhibitors useful in the prophylaxis and/or treatment of a liver disease. It also relates to compositions comprising these IBAT inhibitors, a method for treatment of the disorders and a kit comprising the substances or the compositions. 2. A compound according to claim 1 , chosen from1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N-(carboxymethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N′—((S)-1-carboxyethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxypropyl) carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((R)-1-carboxy-2-methylthioethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxypropyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((R)-1-carboxy-2-methylthio-ethyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine; 1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxy-2-methylpropyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxy-2-(R)-hydroxypropyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxybutyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-Dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N-{(R)-α-[N—((S)-1-carboxyethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1- ...

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Номер записи: 3
24-10-2013 дата публикации

PEPTIDE

Номер: US20130281358A1
Автор: Rauo Jaran
Принадлежит: Marealis AS

The invention provides a peptide comprising or consisting of SEQ ID NO: 1 and variants thereof, particularly comprising of consisting of the sequence FTY, nucleic acids encoding said peptides and pharmaceutical and nutraceutical compositions comprising said peptide(s) and/or nucleic acids. Also provided is the use of such a peptide in therapy and in vitro methods of ACE-inhibition. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. An isolated peptide consisting of the sequence FSY or FTY.8. A pharmaceutical composition comprising a peptide consisting of the sequence FSY or FTY together with a phamaceutically acceptable excipient.9. A pharmaceutical composition comprising(i) peptide of 3-20 amino acids having ACE-inhibitory activity and consisting of or comprising the sequence FSY or FTY; and(ii) a further anti-hypertensive agent.10. A pharmaceutical composition according to claim 9 , wherein said further anti-hypertensive agent is a further peptide having ACE-inhibitory activity and comprising or consisting of the sequence FSY or FTY.11. A nutraceutical composition comprising a peptide consisting of the sequence FSY or FTY together with an excipient or carrier.12. A nutraceutical composition comprising a peptide of 3-20 amino acids having ACE-inhibitory activity and consisting of or comprising the sequence FSY or FTY together with one or more nutraceutical components selected from fat claim 9 , carbohydrates claim 9 , protein claim 9 , fibres claim 9 , ash claim 9 , minerals and vitamins.13. A food or feed comprising a peptide of 3-20 amino acids having ACE-inhibitory activity and consisting of or comprising the sequence FSY or FTY.14. A food or feed according to claim 13 , wherein said food or feed is selected from instant powder products claim 13 , food bars claim 13 , meat and meat analogue products claim 13 , fish and fish analogue products claim 13 , breakfast cereals claim 13 , vegetable fat spreads claim 13 , mayonnaise claim 13 ...

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Номер записи: 4
14-11-2013 дата публикации

Therapeutic or Preventive Agent for Diabetes

Номер: US20130303448A1
Автор: Fumihito Sugihara, Hiroshi Oyama, Naoki Inoue, Seiko Koizumi, Tadashi Yoshimoto
Принадлежит: Nitta Gelatin Inc

A collagen peptide mixture containing three or more kinds selected from Glu-Hyp-Gly, Glu-Hyp, Leu-Hyp-Gly, Pro-Ala, Ser-Hyp, Ala-Hyp-Gly, chemically-modified substances thereof and pharmaceutically acceptable salts thereof, and at least one peptide selected from the group consisting of Glu-Hyp-Gly, Glu-Hyp, Leu-Hyp-Gly, Pro-Ala, Ser-Hyp, Ala-Hyp-Gly, Pro-Hyp-Gly, Leu-Hyp, Ile-Hyp, Ser-Hyp-Gly, Gly-Pro-Hyp, (Pro-Hyp-Gly) 5 , Pro-Hyp, Hyp-Gly, Pro-Gly, Pro-Pro and Ala-Hyp or a chemically-modified substance thereof or a pharmaceutically acceptable salt thereof have DPPTV inhibitory activity and/or GLP-1 secretion accelerating activity, and hence are effective as a therapeutic or preventive agent or the like for diabetes.

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Номер записи: 5
28-11-2013 дата публикации

AMINOSTATIN DERIVATIVES FOR THE TREATMENT OF ARTHROSIS

Номер: US20130316955A1
Автор: Guehring Hans, Klein Markus, Leuthner Brigitta, Tsaklakidis Christos
Принадлежит: Merck Patent GmBH

The present invention relates to compounds of the formula (I) and in particular medicaments comprising at least one compound of the formula (I) for use in the treatment and/or prophylaxis of physiological and/or pathophysiological states in the triggering of which cathepsin D is involved, in particular for use in the treatment and/or prophylaxis of arthrosis, traumatic cartilage injuries, arthritis, pain, allodynia or hyperalgesia. 2. Compounds according to in which{'sup': '1', 'Ris ethyl, n-propyl, isopropyl, cyclopropyl, butyl, isobutyl, sec-butyl, cyclobutyl, tert-butyl, phenyl, benzyl, 2-oxetanyl, 3-oxetanyl, tetrahydrofuran-3-yl, tetrahydrofuran-2-yl, cyclopentyl, pentyl, methylsulfanylmethyl, ethylsulfanylmethyl, 2-methylsulfanylethyl or 1-methylsulfanylethyl,'}and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.3. Compounds according to in which{'sup': '1', 'sub': 2', '2, 'Ais 0 to 4 amino acid radicals which are bonded to one another in a peptide-like manner, selected from the group consisting of alanine, glycine, cyclopropylglycine, cyclobutylglycine, cyclopentylglycine, cyclohexylglycine, 3-oxetanylglycine, 3-oxetanylglycine, tetrahydrofuran-3-ylglycine, tetrahydrofuran-2-ylglycine, ethylsulfanylmethylglycine, 2-methylsulfanylethylglycine, 1-methylsulfanylethylglycine, valine, norvaline, aminobutyric acid, leucine, isoleucine, proline, tert-leucine, norleucine, methionine, phenylalanine, naphthylalanine, O-methylserine, O-ethylserine, —OCO—, —NRCO—, —SO— and —NRSO—,'}and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.4. Compounds according to in which{'sub': '2', 'Ais 0 to 4 amino acid radicals which are bonded to one another in a peptide-like manner, selected from the group consisting of alanine, glycine, cyclopropylglycine, cyclobutylglycine, cyclopentylglycine, cyclohexylglycine, 3- ...

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Номер записи: 6
19-12-2013 дата публикации

COMPOUNDS FOR ENZYME INHIBITION

Номер: US20130338057A1
Автор: BENNETT Mark K., LAIDIG Guy J., PARLATI Francesco, SHENK Kevin D., SMYTH Mark S., Sylvain Catherine, ZHOU Han-jie
Принадлежит:

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention. 1. (canceled)3. The method of claim 2 , wherein Rand Rare independently selected from hydrogen and Calkyl.4. The method of claim 3 , wherein Rand Rare both hydrogen.5. The method of claim 4 , wherein Ris selected from methyl claim 4 , ethyl claim 4 , hydroxymethyl claim 4 , and 2-hydroxyethyl.6. The method of claim 5 , wherein Ris methyl.7. The method of claim 2 , wherein Ris hydrogen.8. The method of claim 2 , wherein L and Q are absent.9. The method of claim 2 , wherein Ris selected from —Calkyl-B and Caralkyl.10. The method of claim 9 , wherein Ris selected from methyl claim 9 , ethyl claim 9 , isopropyl claim 9 , carboxymethyl claim 9 , and benzyl.11. The method of claim 2 , wherein Ris selected from Calkyl-phenyl claim 2 , Calkyl-indolyl claim 2 , Calkyl-thienyl claim 2 , Calkyl-thiazolyl claim 2 , and Calkyl-isothiazolyl.13. The method of claim 2 , wherein Ris selected from Calkyl-phenyl and Calkyl-indolyl.15. The method of claim 2 , wherein Ris selected from heterocyclylMZAZ—Calkyl- claim 2 , heterocyclylM- claim 2 , and carbocyclylM-.16. The method of claim 15 , wherein Ris heterocyclylMZAZ—Calkyl- claim 15 , and heterocyclylM-.17. The method of claim 2 , wherein L is C═O claim 2 , Q is absent claim 2 , M is Calkyl and Ris heterocyclylM- and the heterocyclyl moiety is selected from morpholino claim 2 , piperidino claim 2 , piperazino claim 2 , and pyrrolidino.18. The method of claim 17 , wherein L is C═O claim 17 , Q is absent claim 17 , M is Calkyl and Ris heterocyclylM- and the heterocyclyl moiety is morpholino.19. The method of claim 18 , wherein ...

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Номер записи: 7
06-02-2014 дата публикации

Macrocyclic Compounds and Methods for Their Production

Номер: US20140038885A1
Автор: Gregory Matthew Alan, Moss Steven James, Wilkinson Barrie
Принадлежит: NEUROVIVE PHARMACEUTICAL AB

There is provided inter alia compounds of formula (I): 2. A compound according to wherein n represents a single bond.3. A compound according to claim 1 , wherein Rrepresents OH.4. A compound according to wherein Xrepresents C.5. A compound according to wherein Xrepresents C.6. A compound according to wherein Xrepresents C.7. A compound according to wherein Xrepresents C.8. A compound according to wherein Xrepresents C.9. A compound according to wherein Rrepresents H.10. A compound according to wherein Rrepresents H.11. A compound according to wherein Rrepresents OH.12. A compound according to wherein Rrepresents H claim 1 , Me or F.13. A compound according to wherein Rrepresents H or F.14. A compound according to wherein Rand/or Rrepresents F.15. A compound according to wherein Xrepresents NRR.16. A compound according to wherein Rrepresents alkyl claim 15 , alkenyl claim 15 , cycloalkyl claim 15 , cycloalkenyl claim 15 , alkylcycloalkyl claim 15 , alkylcycloalkenyl claim 15 , alkenylcycloalkyl claim 15 , alkenylcycloalkenyl claim 15 , aryl claim 15 , heteroaryl claim 15 , alkylaryl claim 15 , alkylheteroaryl claim 15 , alkenylaryl or alkenylheteroaryl and Rrepresents H claim 15 , alkyl claim 15 , alkenyl or —Oalkyl.19. (canceled)20. (canceled)21. A pharmaceutical composition comprising a compound according to together with a pharmaceutically acceptable diluent or carrier.22. A pharmaceutical composition comprising a compound according to together with a pharmaceutically acceptable diluent or carrier further comprising a second or subsequent active ingredient.23. A method of treatment of viral infections such as HCV or HIV infection or for use as an immunosuppressant or an anti-inflammatory agent which comprises administering to a subject a therapeutically effective amount of a compound according to . The present invention relates to sanglifehrin analogues, that are useful both as cyclophilin inhibitors, e.g. in the treatment of viral infection by viruses such as ...

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Номер записи: 8
13-02-2014 дата публикации

NOVEL DIPEPTIDYL PEPTIDASE IV (DP-IV) COMPOUNDS

Номер: US20140045771A1
Автор: Chandan Singh, Khamar Bakulesh Mafatlal, Modi Rajiv Indravadan
Принадлежит: Cadila Corporated Campus

The present invention is directed to novel compounds of formula I and pharmaceutically acceptable salts, enantiomers thereof having inhibiting properties of dipeptidyl peptidase IV enzyme (DP-IV inhibitors). The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds along with its composition in the prevention or treatment of diseases associated with DP-IV enzyme. 16-. (canceled)8. The compound as claimed in claim 7 , wherein amino acids are independently selected from glycine claim 7 , alanine claim 7 , valine claim 7 , proline claim 7 , phenylalanine claim 7 , isoleucine claim 7 , histidine or combinations thereof.9. The compound as claimed in claim 7 , wherein at least one of said amino acid is proline claim 7 , alanine or analogous thereof.10. A method for inhibiting dipeptidyl peptidase IV (DP-IV) enzyme in mammal comprising: administering a compound as claimed in . This application is a continuation of U.S. application Ser. No. 13/063,691 filed Apr. 8, 2011, which is the U.S. National Stage filing of International Application Serial No. PCT/IB2009/006807 filed Sep. 11, 2009, which claims priority to Indian Application No. 1934/MUM/2008 filed Sep. 12, 2008 each of which is incorporated herein by reference in its entirety.The invention relates to novel anti-diabetic compounds of formula I and includes their stereo isomers and composition containing compound of formula I as pharmaceutically active ingredient and process for preparation thereofVarious amino peptidases are present in the mammals and catalyze the sequential release of peptidase from peptides such as, pyroglutamyl aminopeptidase and prolylaminpeptidase in addition to dipeptidyl peptidase. Dipeptidyl peptidase family includes DP II, DP-IV, DP VIII, DP IX. (2003, 7, 496) The newly synthesized compounds provide DP-IV inhibition activity sufficiently fast and target rate. The enzyme DP-IV is a part of the CD26 surface region associated with ...

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Номер записи: 9
20-02-2014 дата публикации

NUCLEIC ACID BINDING COMPOUNDS, METHODS OF MAKING, AND USE THEREOF

Номер: US20140050778A1
Автор: Gromova Anna V., Miller Benjamin L., Ofori Leslie O.
Принадлежит: UNIVERSITY OF ROCHESTER

The present invention relates to oligomer compounds, including dimers and trimers, formed by a disulfide, sulfinyl thio, olefin or hydrocarbon bond, or a hydrazone exchange bond between two or more monomers. Methods of making the monomers and the oligomers is also disclosed. Use of the compounds for inhibiting the activity of target RNA molecules, particularly those having a secondary structure that include a stem or stem-loop formation. Dimer compounds capable of inhibiting the activity of an HIV-1 RNA frameshifting stem-loop and a (CUG)n expanded repeat stem-loop are disclosed, as are methods of treating diseases associated with these target RNA molecules. 3. The dimer compound according to claim 1 , wherein Z is a dipeptide claim 1 , a tripeptide claim 1 , or a tetrapeptide.4. The dimer compound according to claim 3 , wherein peptides of the dipeptide claim 3 , tripeptide claim 3 , or tetrapeptide are independently selected from a peptide claim 3 , N-methylated peptide claim 3 , or reduced peptide.56-. (canceled)7. The dimer compound according to claim 1 , wherein the amino acids are selected from Cys claim 1 , His claim 1 , Lys claim 1 , Phe claim 1 , Ala claim 1 , Ser claim 1 , Asp claim 1 , Asn claim 1 , Val claim 1 , Pro claim 1 , Thr claim 1 , Met claim 1 , Gly claim 1 , and D amino acids claim 1 , N-methyl amino acids claim 1 , and pseudo amino acids thereof.8. The dimer compound according to claim 1 , wherein the two monomers are linked together by a disulfide bond or sulfinyl thio linkage.9. The dimer compound according to claim 1 , wherein the two monomers are linked together by an olefin bond.10. (canceled)14. A method of inhibiting HIV-1 proliferation claim 1 , said method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'providing a dimer compound according to and'}contacting an HIV-1 mRNA that encodes Pol polyprotein with the dimer compound under conditions effective to alter normal expression of the Pol polyprotein and thereby inhibit ...

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Номер записи: 10
20-02-2014 дата публикации

Hepatocyte Growth Factor Mimics as Therapeutic Agents

Номер: US20140051633A1
Автор: Benoist Caroline C., Harding Joseph W., Kawas Leen H., Wayman Gary A., Wright John W.
Принадлежит: WASHINGTON STATE UNIVERSITY

Small molecule, peptidic hepatocyte growth factors mimics, which act as both mimetics and antagonists, have been generated. These molecules have been shown or predicted to have therapeutic potential for numerous pathologies including dementia (e.g. Alzheimer's) and Parkinson's disease. 2. The method of claim 1 , wherein said one or more HGF mimics is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide.3. The method of claim 1 , wherein said dementia is Alzheimer's disease dementia.5. The method of wherein said step of administering is performed multiple times over a period of time.6. The method of further comprising the steps of testing cognition of said subject during said period of time claim 5 , and adjusting an amount of said one or more HGF mimics administered based on test results.7. The method of claim 4 , wherein said one or more HGF mimics is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide.9. The method of wherein said one or more HGF mimics is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide.11. The method of claim 1 , wherein said one or more HGF mimics is hexanoic-tyrosine-isoleucine-(6)-amino-hexanoic amide. 1. Field of the InventionThe invention generally relates to methods of using hepatocyte growth factor (HGF) mimics to treat dementia and Parkinson's disease.2. Background of the InventionThere are approximately 10 million diagnosed dementia patients in the United States alone and that number continues to grow every year as the population ages. The costs of treatment and care of these patients are in excess of $70 billion annually and are increasing rapidly. Unfortunately, the current treatment options for the management of dementia are severely limited and largely ineffective. The lack of treatment options for a burgeoning health problem of this magnitude necessitates that new and innovative therapeutic approaches be developed as quickly as possible.At its core dementia results from a combination of diminished synaptic connectivity ...

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Номер записи: 11
13-03-2014 дата публикации

TRYPSIN-LIKE SERINE PROTEASE INHIBITORS, AND THEIR PREPARATION AND USE

Номер: US20140073573A1
Автор: DAGHISH Mohammed, HEROLD Peter, JELAKOVIC Stjepan, Ludwig Friedrich-Alexander, Reichelt Claudia, Schulze Alexander, Schweinitz Andrea
Принадлежит: The Medicines Company (Leipzig) GmbH

The invention provides compounds that are effective as inhibitors of human plasmin and plasma kallikrein, and that are useful for the prevention of blood loss and as components of fibrin adhesives. The invention further provides methods of making and using the compounds. 2. The method according to claim 1 , wherein n is 2 or 3.3. The method according to claim 1 , wherein R is selected from the group consisting of phenyl claim 1 , 4-pyridyl claim 1 , 4-pyridyl N-oxide and 4-piperidinyl.4. The method according to claim 3 , wherein R is selected from the group consisting of unsubstituted phenyl claim 3 , unsubstituted 4-pyridyl claim 3 , unsubstituted 4-pyridyl N-oxide and unsubstituted 4-piperidinyl.5. The method according to claim 1 , wherein n is 0 and R is phenyl.6. The method according to claim 1 , wherein n is 2 or 3 and R is 4-piperidinyl; wherein the nitrogen of said piperidinyl bears a substituent selected from the group consisting of C(═O)R′ claim 1 , C(═O)CHOR′ claim 1 , COR′ claim 1 , C(═O)NHR′ claim 1 , and C(═O)NR′.7. The method according to claim 1 , wherein a pharmaceutical composition is administered to the patient claim 1 , wherein the pharmaceutical composition comprises one or more of the compounds of claim 1 , and one or more pharmaceutically acceptable carriers or excipients.12. A pharmaceutical composition comprising a compound of in combination with one or more pharmaceutically acceptable carriers or excipients.14. A pharmaceutical composition comprising a compound of in combination with one or more pharmaceutically acceptable carriers or excipients. The invention relates to the fields of organic chemistry, serine proteases (particularly plasmin and plasma kallikrein), and hemostasis, and to therapeutic modulation of the blood coagulation cascade and fibrinolysis.Plasmin (EC 3.4.21.7, fibrinolysin) is a trypsin-like serine protease which effects protein cleavage at arginine or lysine residues; its principal substrates are fibrin and ...

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Номер записи: 12
10-04-2014 дата публикации

COMPOUNDS FOR ENZYME INHIBITION

Номер: US20140100169A1
Автор: BENNETT Mark K., LAIDIG Guy J., PARLATI Francesco, SHENK Kevin D., SMYTH Mark S., Sylvain Catherine, ZHOU Han-jie
Принадлежит: Onyx Therapeutics, Inc.

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention. 1. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/646,510, filed Oct. 5, 2012, which is a continuation of U.S. patent application Ser. No. 13/328,909, filed Dec. 16, 2011, issued as U.S. Pat. No. 8,357,683 on Jan. 22, 2013, which is a continuation of U.S. patent application Ser. No. 12/708,753, filed Feb. 19, 2010, issued as U.S. Pat. No. 8,080,545 on Dec. 20, 2011, which is a continuation of U.S. patent application Ser. No. 11/820,490, filed Jun. 19, 2007, issued as U.S. Pat. No. 7,691,852 on Apr. 6, 2010, which claims the benefit of U.S. Provisional Application No. 60/815,218, filed Jun. 19, 2006. The contents of these applications are incorporated herein by reference in their entirety.In eukaryotes, protein degradation is predominately mediated through the ubiquitin pathway in which proteins targeted for destruction are ligated to the 76 amino acid polypeptide ubiquitin. Once targeted, ubiquitinated proteins then serve as substrates for the 26S proteasome, a multicatalytic protease, which cleaves proteins into short peptides through the action of its three major proteolytic activities. While having a general function in intracellular protein turnover, proteasome-mediated degradation also plays a key role in many processes such as major histocompatibility complex (MHC) class I presentation, apoptosis and cell viability, antigen processing, NF-κB activation, and transduction of pro-inflammatory signals.The 20S proteasome is a 700 kDa cylindrical-shaped multicatalytic protease complex comprised of 28 subunits, classified ...

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Номер записи: 13
14-01-2021 дата публикации

PEPTIDOMIMETICS FOR THE TREATMENT OF CORONAVIRUS AND PICORNAVIRUS INFECTIONS

Номер: US20210008150A1
Автор: Amblard Franck, SCHINAZI RAYMOND F., Zandi Keivan
Принадлежит:

Compounds, compositions and methods for preventing, treating or curing a coronavirus, picornavirus, and/or hepeviridae virus infection in human subjects or other animal hosts. Specific viruses that can be treated include enteroviruses. In one embodiment, the compounds can be used to treat an infection with a severe acute respiratory syndrome virus, such as human coronavirus 229E, SARS, MERS, SARS-CoV-1 (OC43), and SARS-CoV-2. In another embodiment, the methods are used to treat a patient co-infected with two or more of these viruses, or a combination of one or more of these viruses and norovirus.

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Номер записи: 14
10-01-2019 дата публикации

INHIBITORS OF HEPATITIS C VIRUS

Номер: US20190008858A1
Автор: Bjornson Kyla, Canales Eda, Cottell Jeromy J., Karki Kapil K., Katana Ashley A., Kato Darryl, Kobayashi Tetsuya, Link John O., Martinez Ruben, Phillips Barton W., Pyun Hyung-jung, Sangi Michael, Schrier Adam J., Siegel Dustin, Taylor James G., Tran Chinh V., Trejo Martin Teresa A., Vivian Randall W., Yang Zheng-Yu, Zablocki Jeff, Zipfel Sheila
Принадлежит:

Compounds of Formula I are disclosed 184.-. (canceled) This application claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application Ser. No. 61/667,806, filed on Jul. 3, 2012, and U.S. Provisional Application Ser. No. 61/798,524, filed on Mar. 15, 2013. The entirety of both applications is incorporated herein by reference.Novel small molecule inhibitors of viral replication are disclosed, compositions containing such compounds, and therapeutic methods comprising the administration of such compounds are also disclosed.The hepatitis C virus (HCV), a member of the hepacivirus genera within the Flaviviridae family, is the leading cause of chronic liver disease worldwide (Boyer, N. et al. 2000, 32, 98-112). Consequently, a significant focus of current antiviral research is directed toward the development of improved methods for the treatment of chronic HCV infections in humans (Ciesek, S., von Hahn T., and Manns, M P., 2011, 15, 597-609, Soriano, V. et al, 2011, 66, 1573-1686; Brody, H., Nature Outlook, 2011, 474, S1-S7; Gordon. C. P., et al., 2005, 48. 1-20; Maradpour, D., et al., 2007, 5, 453-463).Virologic cures of patients with chronic HCV infection are difficult to achieve because of the prodigious amount of daily virus production in chronically infected patients and the high spontaneous mutability of HCV (Neumann, et al., 1998, 282, 103-7; Fukimoto, et al., 1996, 24, 1351-4; Domingo, et al., 1985, 40, 1-8; Martell. et al., 1992, 66, 3225-9). HCV treatment is further complicated by the fact that HCV is genetically diverse and expressed as several different genotypes and numerous subtypes. For example, HCV is currently classified into six major genotypes (designated 1-6), many subtypes (designated a, b, c, and so on), and about 100 different strains (numbered 1, 2, 3, and so on).HCV is distributed worldwide with genotypes 1, 2, and 3 predominate within the United States, Europe, Australia, and East Asia (Japan, Taiwan, Thailand, and China). Genotype 4 ...

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Номер записи: 15
27-01-2022 дата публикации

METHOD FOR SYNTHESIZING PEPTIDES

Номер: US20220024971A1
Автор: SERRE Audrey, YOUTE TENDOUNG Jean-Jacques
Принадлежит: STRAINCHEM

The invention relates to a method for synthesizing peptides or proteins by successively elongating the second end of a peptide chain, the carboxylic acid function (C-terminal) or the amine function Na of which is attached to an anchoring molecule that is soluble in an apolar solvent, characterized in that said anchoring molecule comprises a polyolefin chain with at least 10 monomer units, and preferably between 15 and 50 units. 1. A method for synthesizing peptides or proteins by successively elongating the second end (Nα) of a peptide chain of which the first end is attached to an anchoring molecule that is soluble in an apolar solvent by means of the carboxylic acid function (C-terminus) thereof or the amine function (Nα) thereof , characterized in that said anchoring molecule includes a polyolefin chain with at least 10 monomer units and preferably between 15 and 50 units.2. The method according to claim 1 , characterized in that said anchoring molecule only includes one polyolefin chain.3. The method according to claim 1 , characterized in that said polyolefin chain is a polyisobutene chain.4. The method according to one of claim 1 , characterized in that said anchoring molecule is a polyolefin.5. The method according to one of claim 1 , characterized in that said polyolefin chain is functionalized at one of the ends thereof.6. The method according to one of claim 1 , characterized in that said polyolefin chain comprises a number of unsaturated carbon-carbon bonds not exceeding 5% and preferably not exceeding 3%.7. The method according to one of claim 1 , characterized in that said polyolefin chain has an average molecular weight by mass of between 600 and 20 claim 1 ,000 claim 1 , and preferably between 700 and 15 claim 1 ,000.8. The method according to one of claim 1 , characterized in that said anchoring molecule includes a polyolefin chain (or is a polyolefin chain) terminated by a group selected from the group consisting of:{'sub': '2', 'a —X function, ...

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Номер записи: 16
14-01-2021 дата публикации

HYBRID LIGAND, HYBRID BIOMIMETIC CHROMEDIA AND PREPARING METHOD AND USE THEREOF

Номер: US20210009635A1
Автор: LIN Dongqiang, LU Huili, YAO Shanjing, ZHANG QILEI, ZOU Xujun
Принадлежит: Zhejiang University

This invention relates to a hybrid ligand, a hybrid biomimetic chromedia and a preparing method and a use thereof, wherein the hybrid biomimetic chromedia takes hydrophilic porous microsphere as a substrate in chromatography, activated with allyl bromide and undergoing bromo-alcoholization with N-bromosuccinimide, then coupled with the hybrid ligands. The sequence of the hybrid ligand is phenylalanine-tyrosine-glutamine-5-aminobenzimidazole. The hybrid biomimetic chromedia has both of the two functional groups of phenylalanine-tyrosine-glutamine tripeptide and aminobenzimidazole, while maintaining the high antibody selectivity of polypeptide ligand, hydrophobic electric charge inductive ligand is introduced to achieve more moderate elution requirement, realizing effective antibody separation. 3. The hybrid biomimetic chromedia according to claim 2 , wherein the substrate in chromatography is sepharose gel or cellulose microsphere.4. A method for preparing the hybrid biomimetic chromedia according to claim 2 , comprising the following steps:1) performing an activating reaction by subjecting the substrate in chromatography with allyl bromide to obtain an activated substrate in chromatography;2) performing a bromo-alcoholization reaction by subjecting the activated substrate in chromatography with N-bromosuccinimide to obtain a bromo-alcoholized substrate;3) performing a coupled reaction by subjecting the bromo-alcoholized substrate and the hybrid ligand to obtain the hybrid biomimetic chromedia.5. The method according to claim 4 , wherein the activating reaction in Step 1) comprises: mixing the substrate in chromatography claim 4 , a dimethyl sulfoxide solution claim 4 , allyl bromide and sodium hydroxide claim 4 , and conducting water bath reaction in a shaker claim 4 , leaching and washing to obtain the activated substrate in chromatography.6. The method according to claim 4 , wherein the bromo-alcoholization reaction in Step 2) comprises: mixing the activated ...

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Номер записи: 17
09-01-2020 дата публикации

AMIDE COMPOUND

Номер: US20200010487A1
Автор: Fukase Yoshiyuki, Fukumoto Shoji, Ishii Naoki, Kono Mitsunori, Ochida Atsuko, Oda Tsuneo, Sasaki Yusuke, Sato Ayumu, SHIRAI Junya, Tokuhara Hidekazu, Tomata Yoshihide, YAMAMOTO Satoshi
Принадлежит:

The present invention relates to compound (I) or a salt thereof which has a RORγt inhibitory action. In the formula (I), each symbol is as defined in the specification. 116-. (canceled)18. The method of claim 17 , wherein the substituent that Ring A optionally further has is a fluorine atom or a chlorine atom.19. The method of claim 17 , wherein Ris a tert-butyl group claim 17 , a neopentyl group or a trimethylsilyl group.21. The method of claim 17 , wherein Ris a hydrogen atom or a methyl group.22. The method of claim 17 , wherein the compound is (3S)—N-((1R)-2-((4-tert-Butyl-3-fluorophenyl)amino)-1-(4 claim 17 ,4-difluorocyclohexyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide or a salt thereof.23. The method of claim 17 , wherein the compound is N-((1R)-2-((3 claim 17 ,5-Difluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methyl-1 claim 17 ,2-oxazole-5-carboxamide or a salt thereof.24. The method of claim 17 , wherein the compound is (2R)—N-(4-tert-Butyl-3 claim 17 ,5-difluorophenyl)-2-(((3-hydroxy-1 claim 17 ,2-oxazol-5-yl)acetyl)amino)-2-(1-methyl-1H-indazol-5-yl)acetamide or a salt thereof.25. The method of claim 17 , wherein the compound is (3R)—N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide or a salt thereof.26. The method of claim 17 , wherein the compound is selected from the group consisting of(3S)—N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide,N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methyl-1,2-oxazole-5-carboxamide,N-(2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide,(2R)-2-(((2,4-dioxo-3,4-dihydropyrimidin-1 (2H)-yl)acetyl)amino)-N-(3-fluoro-4-(trimethylsilyl)phenyl)-2-(4-(methoxymethyl)phenyl)acetamide,(2R)—N-(3-fluoro-4-(trimethylsilyl)phenyl)-2-(4 ...

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Номер записи: 18
19-01-2017 дата публикации

THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE

Номер: US20170015703A1
Автор: Cai Zhenwei, Cui Dawei, Lemieux Rene M., Popovici-Muller Janeta, Travins Jeremy, ZHOU Ding
Принадлежит:

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here. 2. The compound of claim 1 , wherein:{'sup': 1', '7, 'sub': 4', '6, 'Ris C-Ccarbocyclyl optionally substituted with one to three Rgroups;'}{'sup': 2', '3', '7, 'each Rand Ris independently selected from aryl or heteroaryl, wherein said aryl or heteroaryl is independently optionally substituted with one to three Rgroups;'}{'sup': 4', '7, 'Ris alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, wherein said aryl, heteroaryl, aralkyl, and heteroaralkyl are each independently optionally substituted with one to three Rgroups;'}{'sup': '5', 'ring A is 4-6 membered non-aromatic ring having 0-1 additional heteroatoms selected from N, O or S, wherein ring A is optionally substituted with one or two Rgroups;'}{'sup': 5', '7', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6, 'sub': 3', '2', '1', '4', '1', '4', '1', '4', '2', '1', '4', '2', '2', '2', '1-4', '2', '1', '4', '2', '3', '5', '3', '6', '1', '4', '1', '4', '1', '4, 'each Rand Ris independently halo; —CF; —CN; —OR; —N(R); —C(O)C-Calkyl; C-Chaloalkyl; C-Calkyl optionally substituted with —ORor —N(R); —O—C-Calkyl optionally substituted with halo, —ORor —N(R); —SON(R); —S(O)—Calkyl; —SO(C-Calkyl); —NRSOR; C-Ccarbocyclyl optionally substituted with one or two Rgroups; —O—(C-Ccarbocyclyl optionally substituted with one or two Rgroups); 5-6 membered heteroaryl; —C-Calkyl-C(O)O—C-Calkyl; or —C(O)O—C-Calkyl; or'}{'sup': '6', 'sub': 1', '4, 'each Ris independently H or C-Calkyl.'}3. The compound of claim 1 , wherein each Rand Ris independently aryl optionally substituted with one to three Rgroups.5. The compound of claim 1 , wherein Ris Cor Ccycloalkyl optionally substituted with one to two Rgroups and Rassociated with Ris halo.9. The compound of claim 7 , wherein Ris aryl or heteroaryl claim 7 , each aryl or heteroaryl is optionally ...

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Номер записи: 19
19-01-2017 дата публикации

PROLINE COMPOUNDS AS GRANZYME B INHIBITORS

Номер: US20170015706A1
Автор: Cameron Dale R.
Принадлежит: viDA Therapeutics Inc.

Proline compounds as Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Methods for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided. 6. The compound of claim 5 , or stereoisomer claim 5 , tautomer claim 5 , or pharmaceutically acceptable salt thereof claim 5 , wherein:{'sub': 10', '1', '12, 'R, when defined as C-Calkyl substituted with a carboxylic acid or carboxylate group, is{'sub': 2', 'n', '2, '—(CH)—COH, where n is 2, 3, 4, 5, or 6;'}{'sub': 1', '3', '6', '10, 'optionally wherein one or more single methylene carbons are substituted with a fluoro, hydroxy, amino, C-Calkyl, or C-Caryl group;'}{'sub': 1', '3, 'optionally wherein one or more single methylene carbons are substituted with two fluoro or C-Calkyl groups;'}optionally wherein one or more single methylene carbons are substituted with two alkyl groups that taken together with the carbon to which they are attached form a 3-, 4-, 5-, or 6-membered carbocyclic ring; oroptionally wherein adjacent carbon atoms from an unsaturated carbon-carbon bond or taken together form a benzene ring.8. The compound of claim 5 , or stereoisomer claim 5 , tautomer claim 5 , or pharmaceutically acceptable salt thereof claim 5 , wherein:{'sub': '1', 'Ris tetrazole or triazole;'}{'sub': 2', '2, 'Ra is hydrogen and Rb is selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, hydroxy, C1-C6 alkoxy, aryloxy, aralkoxy, alkylthio, arylthio, arylsulfonyl, and aryl sulfinyl;'}{'sub': 3', '1', '4', '1', '4, 'Ris hydrogen; C-Calkyl optionally substituted with a carboxylic acid, carboxylate, or a carboxylate ester group; or C-Calkyl optionally substituted with an amide, which may be optionally substituted with an alkylheteroaryl group;'}{'sub': 4', '1', '12', '3', '6', '6', '10', '3', '10, 'Ris C-Calkyl, C-Ccycloalkyl, C-Caryl, ...

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Номер записи: 20
28-01-2016 дата публикации

DEPROTECTION METHOD

Номер: US20160024143A1
Автор: Monguchi Yasunari, Sajiki Hironao
Принадлежит: AJINOMOTO CO., INC.

The present invention provides a method of efficiently deprotecting a protected organic compound by catalytic hydrogenation. Specifically, the present invention provides a method of deprotecting an organic compound having at least one functional group selected from the group consisting of a carboxy group, an amino group and a hydroxy group, which is protected by a protecting group represented by the formula (I): 2. The method according to claim 1 , wherein said halogenated acetic acid is at least one member selected from the group consisting of trichloroacetic acid claim 1 , dichloroacetic acid claim 1 , monochloroacetic acid claim 1 , trifluoroacetic acid claim 1 , difluoroacetic acid claim 1 , and monofluoroacetic acid.3. The method according to claim 1 , wherein said hydrogenation is conducted in the presence of trifluoroacetic acid.4. The method according to claim 1 , wherein said hydrogenation is conducted in the presence of said halogenated acetic acid in an amount of not less than 1 mol per 1 mol of total sulfur atom contained in said sulfur-containing peptide.5. The method according to claim 1 , wherein said metal catalyst is at least one member selected from the group consisting of a nickel catalyst claim 1 , a copper catalyst claim 1 , a ruthenium catalyst claim 1 , a palladium catalyst claim 1 , a rhodium catalyst claim 1 , and a platinum catalyst.6. The method according to claim 1 , wherein said hydrogenation is conducted in the presence of a palladium catalyst.7. The method according to claim 6 , wherein said hydrogenation is conducted in the presence of palladium carbon.8. The method according to claim 1 , wherein Ris a phenyl group optionally having one or more substituent(s).9. The method according to claim 1 , wherein said protecting group is selected from the group consisting of:a benzyl group optionally having one or more substituent(s),a benzhydryl group optionally having one or more substituent(s),a trityl group optionally having one or more ...

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Номер записи: 21
26-01-2017 дата публикации

TRIPEPTIDE EPOXYKETONE COMPOUND CONSTRUCTED BY HETEROCYCLE AND PREPARATION METHOD AND USE THEREOF

Номер: US20170022250A1
Автор: HE Qiaojun, HU Xiaobei, HU Yongzhou, Li Jia, Liu Tao, Xu Lei, Yang Bo, ZHANG Jiankang, ZHOU Yubo
Принадлежит:

Disclosed are a tripeptide epoxyketone compound, a preparation method thereof, and a use thereof in the preparation of anti-tumor drugs. 3. The compound according to claim 2 , characterized in that the compound is:4-(pyrazin-2-yl carbamoyl)piperidin-1-oyl-Phe-Leu-Leu-epoxy ketone;1-(pyrazin-2-oyl)piperidin-4-oyl-Phe-Leu-Leu-epoxy ketone;4-(pyrazin-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;1-(pyrazin-2-oyl)piperidin-4-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyrazin-2-oyl)piperazin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyrazin-2-formamido)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-fluorophenyl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-benzoyl phenyl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(biphenyl-4-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-chlorophenyl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-methoxy phenyl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(isoxazol-3-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(thiazol-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(1,3,4-thiadizol-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(benzo[d]thiazol-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyridin-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyridin-3-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyridin-4-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(pyrimidin-2-yl carbamoyl)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;1-(4-chlorophenyl carbamoyl)piperidin-4-oyl-Leu-Phe-Leu-epoxy ketone;1-(4-methoxy phenyl carbamoyl)piperidin-4-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-chlorophenyl carbamoyl)piperazin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-methoxy phenyl carbamoyl)piperazin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-chloro benzamido)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-methoxy benzamido)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-chlorophenyl uramido)piperidin-1-oyl-Leu-Phe-Leu-epoxy ketone;4-(4-methoxy phenyl uramido)piperidin ...

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Номер записи: 22
17-04-2014 дата публикации

METHODS AND COMPOSITIONS FOR TREATING AMYLOID-RELATED DISEASES

Номер: US20140107027A1
Автор: Gervais Francine, KONG Xianqi, MIGNEAULT David, VALADE Isabelle, WU Xinfu
Принадлежит: BHI LIMITED PARTNERSHIP

Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease. 1232-. (canceled)234. The compound of claim 233 , wherein Ris hydrogen.235. The compound of claim 233 , wherein Ris straight chain alkyl.236. The compound of claim 233 , wherein Ris t-butyl.237. The compound of claim 233 , wherein Ris carbocyclic.238. The compound of claim 233 , wherein Ris C-Cbicycloalkyl.239. The compound of claim 233 , wherein said bicyclic fused ring group is indolyl.240. The compound of claim 233 , wherein Lis CHCHor absent.251. A method of treating or preventing an amyloid-related disease in a subject comprising administering to a subject in need thereof a compound of in an amount effective to treat or prevent an amyloid related disease.252. The method according to claim 251 , wherein said amyloid-related disease is Alzheimer's disease claim 251 , cerebral amyloid angiopathy claim 251 , inclusion body myositis claim 251 , macular degeneration claim 251 , MCI claim 251 , or Down's syndrome.253. The method according to claim 251 , wherein amyloid fibril formation or deposition claim 251 , neurodegeneration claim 251 , microglial inflammatory response claim 251 , or cellular toxicity is reduced or inhibited upon administration of said compound.254. The method according to claim 251 , wherein said amyloid-related disease is diabetes claim 251 , AA amyloidosis claim 251 , AL amyloidosis claim 251 , or hemodialysis related amyloidosis (βM).255. The method of claim 251 , wherein said subject has Alzheimer's disease claim 251 , Mild Cognitive Impairment claim 251 , or cerebral amyloid angiopathy claim 251 , and stabilization of cognitive function claim 251 , prevention of a further decrease in cognitive function claim 251 , or prevention claim 251 , slowing claim 251 , or stopping of disease progression occurs in said patient upon administration.256. A method for inhibiting amyloid deposition in a subject comprising administering ...

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Номер записи: 23
10-02-2022 дата публикации

BIOINSPIRED HIGHLY THERMO-SUSTAINABLE PACKINGS WITH USES THEREOF

Номер: US20220041651A1
Автор: Gazit Ehud, GILEAD Sharon, LAZAR Sigal, Tao Kai
Принадлежит:

A thermally stable composition having at least one aromatic cyclic di-peptide is provided having a thermal sustainability of up to 680 Kelvin. The thermally stable compositions can be used in high temperature applications. 1. A thermally stable composition comprising at least one aromatic cyclic di-peptide , wherein the composition has a thermal sustainability of up to 680 Kelvin.2. The composition of claim 1 , wherein said at least one aromatic cyclic dipeptide is a simple aromatic cyclic dipeptide.3. The composition of claim 2 , wherein said at least one simple aromatic dipeptide is a cyclo-ditryptophan.4. The composition of claim 1 , wherein the composition is a nanostructure composition comprising monomers of the at least one aromatic cyclic di-peptide.5. The composition of claim 1 , wherein said composition has a thermal sustainability of about 580 Kelvin to about 680 Kelvin.6. The composition of claim 1 , wherein said composition has a thermal sustainability of about 630 Kelvin to about 680 Kelvin.7. The composition of claim 1 , wherein said composition has a thermal sustainability of about 650 Kelvin to about 680 Kelvin.8. The composition of claim 1 , wherein said at least one aromatic cyclic dipeptide comprises a plurality of aromatic cyclic dipeptide molecules forming a self-assembled structure.9. The composition of claim 1 , wherein said composition has a thermal quenching activity energy of up to 0.11 eV.10. The composition of claim 1 , wherein said composition has a thermal quenching activity energy of about 0.03 eV to about 0.11 eV.11. The composition of claim 1 , wherein said at least one aromatic cyclic dipeptide comprises at least one indole ring.12. The composition of claim 11 , wherein said at least one indole ring comprises one or more substituent groups that modulate said thermal sustainability of the composition.13. A semiconductor system claim 11 , comprising a self-assembled structure formed of one or more cyclic peptides claim 11 , wherein ...

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Номер записи: 24
24-01-2019 дата публикации

THERAPEUTIC COMPOSITIONS INCLUDING PHENAZINE-3-ONE AND PHENOTHIAZINE-3-ONE DERIVATIVES AND USES THEREOF

Номер: US20190023738A1
Автор: Wilson D. Travis
Принадлежит:

Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of phenazine-3-one and/or phenothiazine-3-one derivatives, analogues, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide). The present technology provides compositions related to aromatic-cationic peptides linked to phenazine-3-one or phenothiazine-3-one derivatives and uses of the same. In some embodiments, the aromatic-cationic peptide comprises D-Arg-2′6′-Dmt-Lys-Phe-NH. 1. A composition comprising a phenazine-3-one and/or phenothiazine-3-one derivative as described in Section I in combination with one or more aromatic-cationic peptides disclosed in Section II.2. The composition of claim 1 , further comprising one or more additional active agents such as cyclosporine claim 1 , a cardiac drug claim 1 , an anti-inflammatory claim 1 , an anti-hypertensive drug claim 1 , an antibody claim 1 , an ophthalmic drug claim 1 , an antioxidant claim 1 , a metal complexer claim 1 , and an antihistamine.3. A method for:(a) treating or preventing a disease or condition,(b) reducing CD36 expression in a subject in need thereof,(c) treating or preventing a disease or condition characterized by CD36 elevation in a subject in need thereof,(d) reducing oxidative damage in a removed organ or tissue,(e) preventing the loss of dopamine-producing neurons in a subject in need thereof,(f) reducing oxidative damage associated with a neurodegenerative disease in a subject in need thereof,(g) preventing or treating a burn injury in a subject in need thereof,(h) treating or preventing mechanical ventilation-induced diaphragm dysfunction in a subject in need thereof,(i) treating or preventing no reflow following ischemia-reperfusion injury in a subject in need thereof,(j) preventing norepinephrine uptake in a subject in need of analgesia,(k) treating or preventing drug-induced ...

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Номер записи: 25
23-01-2020 дата публикации

ANTIGENIC TRIPEPTIDES DERIVED FROM MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS S-TYPE STRAINS, DERIVATIVES AND USES THEREOF

Номер: US20200024307A1
Автор: Bannantine John P., BAY Sylvie, BIET Franck, ETIENNE Gilles
Принадлежит:

The present invention is directed to an isolated synthetic tripeptide of formula H-D-Phe-N-Methyl-L-Val-L-Ala-OMe (SEQ ID NO:1), or a derivative thereof, and to the corresponding lipotripeptides, which are specific to subsp. (Map) S-type strain, as well as derivatives and conjugates thereof. The invention also concerns the use of these antigens in different methods and tests for detecting Map infection, especially by detecting humoral response and cell mediated response of infected animals. The invention is also directed to a genetic signature of Map and a mass spectrometry and NMR spectroscopy signature of Map presence or infection. 1. An isolated synthetic tripeptide chosen from the group consisting in:a. a tripeptide of formula H-D-Phe-N-Methyl-L-Val-L-Ala-OMe (SEQ ID NO:1),b. a tripeptide of formula H-L-Phe-N-Methyl-L-Val-L-Ala-OMe (SEQ ID NO:2),c. a tripeptide of formula H-D-Phe-L-Val-L-Ala-OMe (SEQ ID NO:3);d. a tripeptide of formula H-D-Phe-N-Methyl-L-Val-L-Ala-OH (SEQ ID NO:4);e. a tripeptide of formula H-L-Phe-L-Val-L-Ala-OMe (SEQ ID NO:5);f. a tripeptide of formula H-D-Phe-L-Val-L-Ala-OH (SEQ ID NO:6);g. a tripeptide of formula H-L-Phe-N-Methyl-L-Val-L-Ala-OH (SEQ ID NO:7) andh. a tripeptide of formula H-L-Phe-L-Val-L-Ala-OH (SEQ ID NO:8).2. An isolated synthetic tripeptide variant of the tripeptide according to claim 1 , which is derived from the tripeptide by substitution of the L-Val by D-Val and/or substitution of L-Ala by D-Ala claim 1 , and/or N-alkylation of one or more of Phe claim 1 , Val and Ala claim 1 , and/or the retro-inverso sequence and/or a peptidomimetic of the tripeptide with modified backbone or linkage.3. An isolated synthetic tripeptide conjugate consisting in or comprising a tripeptide according to claim 1 , wherein the Phenylalanine at the N-terminus is N-acylated with a Cto Cacyl moiety claim 1 , which is not a fatty acid moiety.4. An isolated synthetic tripeptide conjugate consisting in or comprising a tripeptide according to ...

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Номер записи: 26
29-01-2015 дата публикации

HCV PROTEASE INHIBITORS AND USES THEREOF

Номер: US20150031106A1
Автор: Kluge Arthur F., Niu Deqiang, Petter Russell C., Qiao Lixin, Singh Juswinder
Принадлежит: CELGENE AVILOMICS RESEARCH, INC.

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same. 147-. (canceled)49. The conjugate according to claim 48 , wherein:{'sub': 2-8', '2', '2', '2, 'L is a bivalent Cstraight or branched, hydrocarbon chain wherein L has at least one double bond and at least one methylene unit of L is replaced by —C(O)—, —NRC(O)—, —C(O)NR—, —N(R)SO—, —SON(R)—, —S(O)—, —SO—, —OC(O)—, or —C(O)O—, and one additional methylene unit of L is optionally replaced by —C(O)—; and'}{'sub': 1-6', '2, 'Y is hydrogen or Caliphatic optionally substituted with oxo, halogen, NO, or CN.'}50. The conjugate according to claim 48 , wherein L is a bivalent Cstraight or branched claim 48 , hydrocarbon chain wherein L has at least one double bond and at least one methylene unit of L is replaced by —C(O)— claim 48 , and one additional methylene unit_of L is optionally replaced by cyclopropylene claim 48 , —O— claim 48 , —N(R)— claim 48 , or —C(O)—.51. The conjugate according to claim 49 , wherein L is a bivalent Cstraight or branched claim 49 , hydrocarbon chain wherein L has at least one double bond and at least one methylene unit of L is replaced by —OC(O)—.52. The conjugate according to claim 48 , wherein L is —NRC(O)CH═CH— claim 48 , —NRC(O)CH═CHCHN(CH)— claim 48 , —NRC(O)CH═CHCHO— claim 48 , —NRSOCH═CH— claim 48 , —NRSOCH═CHCH— claim 48 , —NRC(O)C(═CH)CH— claim 48 , or —CHNRC(O)CH═CH—; wherein R is H or optionally substituted Caliphatic; and Y is hydrogen or Caliphatic optionally substituted with oxo claim 48 , halogen claim 48 , NO claim 48 , or CN.53. The conjugate according to claim 52 , wherein L is —NHC(O)CH═CH— claim 52 , —NHC(O)CH═CHCHN(CH)— claim 52 , —NHC(O)CH═CHCHO— claim 52 , —NHSOCH═CH— claim 52 , —NHSOCH═CHCH— claim 52 , —NHC(O)C(═CH)CH— claim 52 , or —CHNHC(O)CH═CH—.54. The conjugate according to claim 48 , wherein L is a bivalent Cstraight or branched claim 48 , hydrocarbon chain wherein L has at least one alkylidenyl ...

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Номер записи: 27
04-02-2016 дата публикации

SMALL MOLECULE MODULATORS OF PCSK9 AND METHODS OF USE THEREOF

Номер: US20160031935A1
Автор: CHIASSON JEAN-FRANCOIS, Crane Sheldon, Guay Daniel, LACHANCE NICOLAS, Lacombe Patrick, Seidah Nabil G., SKOREY KATHRYN, Truong Vouy Linh
Принадлежит:

A compound of Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, or racemic mixture or stereoisomer thereof, and methods for preventing or treating an LDL-cholesterol-related disease or disorder using such compound(s), and kits and compositions comprising such compound(s). 2. The compound of claim 1 , wherein:(A){'sub': b', 'c', 'a, 'a. R1 is —B(OR)(OR), or —CH(OH)R;'}{'sub': 2', '2', 'm', 'j, 'b. R2 is H or —CH(CH)C(O)R;'}c. R3 is H or C1-6 alkyl substituted or not;d. R4 is H, C1-6 alkyl substituted or not, C1-6 thioalkyl substituted or not, aryl substituted or not or cycloalkyl substituted or not;e. R5 is H;f. R6 is H, C1-6 alkyl substituted or not, C1-6 thioalkyl substituted or not, aryl substituted or not, or cycloalkyl substituted or not;g. R7 is H;h. R8 is H, C1-6 alkyl substituted or not, C1-6 thioalkyl substituted or not, aryl substituted or not, or cycloalkyl substituted or not; and/or{'sub': m', 'i', 'm', 'i', 'i', 'n, 'i. R9 is RiOC(O)—, RiC(O)—, RORC(O)—, RC(O)RC(O)— or RS(O)—; or'}(B){'sub': b', 'c', 'a, 'a. R1 is —B(OR)(OR) or —CH(OH)R;'}{'sub': 2', '2', 'j, 'b. R2 is H or —CH(CH)C(O)R;'}c. R3 is H or C1-6 alkyl substituted or not;d. R4 is H, C1-6 alkyl substituted or not, C1-6 thioalkyl substituted or not, aryl substituted or not or cycloalkyl substituted or not;e. R5 is H;f. R6 is H, C1-6 alkyl substituted or not, C1-6 thioalkyl substituted or not, aryl substituted or not, or cycloalkyl substituted or not;g. R7 is H;h. R8 is H, C1-6 alkyl substituted or not, C1-6 thioalkyl substituted or not, aryl substituted or not, or cycloalkyl substituted or not; and{'sub': m', 'i', 'm', 'i', 'i', 'n, 'i. R9 is RiOC(O)—, RiC(O)—, RORC(O)—, RC(O)RC(O)—, RS(O)—.'}3. (canceled)4. The compound of claim 1 , wherein:{'sub': b', 'c', 'a, 'a. R1 is —B(OR)(OR) or —CH(OH)R;'}{'sub': 2', '2', 'm', 'j, 'b. R2 is H or —CH(CH)C(O)R;'}c. R3 is H or C1-6 alkyl substituted or not;d. R4 is H, C1-6 alkyl substituted or not, C1-6 thioalkyl substituted or not, aryl ...

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Номер записи: 28
05-02-2015 дата публикации

MODULATORS OF PROTEASE ACTIVATED RECEPTORS

Номер: US20150038402A1
Автор: Fairlie David Paul, Liu Ligong, Reid Robert, Suen Jacky Yung, Yau Mei Kwan
Принадлежит:

The present application provides novel compounds of the Formula (I), pharmaceutical compositions comprising such compounds and methods for using such compounds as tools for biological studies or as agents or drugs for modulating Protease Activated Receptor- (PAR) and for treating a subject at risk of—or susceptible to—a disease or disorder, or having a disease or disorder associated with undesirable PAR activity. 6. The method according to claim 1 , wherein said compound is:5-isoxazoyl-Cha-Ile-aminomethylphenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-methoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3-methoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(4-methoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-methyl)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-ethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-propoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-isopropoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-butoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-isobutoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-chloro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-nitro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-trifluoromethyl)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3-trifluoromethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-trifluoromethyl)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-fluoro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3-fluoro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(4-fluoro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(1,3-dioxalane)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3,4-dichloro)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,4-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,5-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3,4-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,3-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,3,4-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,6-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2-methoxy-5-trifluoromethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(2,4-dimethoxy)phenyl;5-isoxazoyl-Cha-Ile-aminomethyl-(3,5-bis(trifluoromethyl ...

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Номер записи: 29
09-02-2017 дата публикации

SYNTHETIC PEPTIDES, ENZYMATIC FORMATION OF PERICELLULAR HYDROGELS/NANOFIBRILS, AND METHODS OF USE

Номер: US20170037082A1
Автор: Kuang Yi, Shi Junfeng, Xu Bing
Принадлежит:

Disclosed are peptides that contain up to about 35 amino acids, including a plurality of aromatic amino acid residues and either (i) an amino acid residue that is phosphorylated or sulfated, or (ii) an amino acid comprising an ester-moiety linked via peptide bond, or both (i) and (ii), wherein the peptide is capable of self-assembly to form nanofibrils in the presence of an enzyme that hydrolyzes the phosphate group, the sulfate group, or the ester-moiety. These peptides are enzymatically responsive hydrogelators, and they can be used to form pericellular hydrogels/nanofibrils upon exposure to target cells that secrete or express a surface bound ectoenzyme having hydrolase activity suitable to induce peptide gelation. These materials, and compositions containing the same, can be used for in vitro and in vivo cellular imaging, treating cancerous conditions, collecting a secretome from a cell upon which the pericellular hydrogels/nanofibrils form, and screening the collected secretome. 1. A peptide comprising up to about 35 amino acids , including a plurality of aromatic amino acid residues and either (i) an amino acid residue that is phosphorylated or sulfated , or (ii) an amino acid comprising a covalently bound ester-moiety , or both (i) and (ii) , wherein , upon exposure to a cell that expresses an ectoenzyme that hydrolyzes the phosphate group , the sulfate group , or the ester-moiety , the peptide self-assembles to form nanofibrils externally of the cell.2. The peptide according to claim 1 , wherein the aromatic amino acids are selected from the group consisting of phenylalanine claim 1 , phenylalanine derivatives claim 1 , napthylalanine claim 1 , napthylalanine derivative claim 1 , tyrosine claim 1 , tyrosine derivatives claim 1 , tryptophan claim 1 , and tryptophan derivatives.3. The peptide according to claim 1 , wherein the amino acids are all D-amino acids or all L-amino acids.4. The peptide according to claim 1 , wherein the amino acids are a mixture of L ...

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Номер записи: 30
08-02-2018 дата публикации

METHODS OF MAKING CARFILZOMIB AND INTERMEDIATES THEREOF

Номер: US20180037606A1
Автор: Ahmed Saiyed Akeel Ahmed Shakeel, Bobbili Veerabhadra Rao, Chowdary Talluri Bhushaiah, Dusanapudi N V Raghavalu, Kannapan Jayaraman, Kovi Ravishanker, Kulkarni Gaurav, Mantri Anand V., Prasad Alaparthi Lakshmi, Ramu Vasanthakumar G.
Принадлежит: Apicore US LLC

Racemization-free methods are disclosed for the synthesis of carfilzomib. Novel intermediates and methods of making carfilzomib employing fragment condensation using the novel intermediates are disclosed. Amorphous carfilzomib and methods of making same are disclosed. 2. A compound according to comprising an active ester.3. A compound according to obtained from a corresponding hydroxy compound and/or substituted phenol.4. A method of making an active ester compound according to comprising obtaining a free acid of a compound of formula I and activating a resulting intermediate using a hydroxy and/or phenolic compound.5. The method according to wherein the step of obtaining a free acid is selected from one or more of bis-silylation claim 4 , using at least one silylating agent and an organic base claim 4 , and/or hydrolysis of esters by using at least one alkali metal hydroxide selected from NaOH claim 4 , KOH claim 4 , LiOH and their corresponding carbonates.6. The method according to comprising isolating a compound of formula I using an organic solvent. This application is a continuation of U.S. patent application Ser. No. 14/923,068 filed Oct. 26, 2015 and claims the benefit of U.S. Provisional Application No. 62/068,928 filed Oct. 27, 2014, the entireties of which are incorporated herein by reference.The presently disclosed subject matter relates to the synthesis of carfilzomib.Carfilzomib, an epoxomicin derivative, is a selective proteasome inhibitor. Carfilzomib is used to treat patients with multiple myeloma who have already been treated with at least two other medications.Novel methods and intermediates are disclosed for the production of carfilzomib. Processes disclosed herein may be employed to produce amorphous form carfilzomib.In one or more embodiments methods employ a fragment-based approach involving active esters. For example, active esters obtained from hydroxyl-benzotriazoles, hydroxy-aza-benzotriazoles, succinimide esters, substituted phenols, etc. ...

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Номер записи: 31
12-02-2015 дата публикации

COMPOSITIONS CONTAINING DELTA-9-THC-AMINO ACID ESTERS AND PROCESS OF PREPARATION

Номер: US20150045282A1
Автор: Ashfaq Mohammad Khalid, Elsohly Mahmoud A., Gul Waseem, Majumdar Soumyajit, Repka Michael A.
Принадлежит:

Suppository, hot melt and ophthalmic formulations containing amino esters of the formulae (I), (II) and (III), where R1, R2 and R3 are residues of amino acids such as, but not limited to, valine, sarcosine, leucine, glutamine, tryptophan, tyrosine, alanine and 4(4-aminophenyl)butyric acid or combination thereof, and salts thereof. 4. The suppository formulation for effecting bioavailability of Δ-THC for the treatment of any disease condition responsive to Δ-THC containing a hemisuccinate or hemigluturate derivative of the Δ-THC amino ester compounds of .5. The suppository formulation for effecting bioavailability of Δ-THC for the treatment of any disease condition responsive to Δ-THC containing a hemisuccinate or hemigluturate derivative of the Δ-THC amino ester compounds of .6. The suppository formulation for effecting bioavailability of Δ-THC for the treatment of any disease condition responsive to Δ-THC containing a hemisuccinate or hemigluturate derivative of the Δ-THC amino ester compounds of .7. The suppository formulation according to where Ris valine claim 1 , sarcosine claim 1 , leucine claim 1 , glutamine claim 1 , tryptophan claim 1 , tyrosine claim 1 , or alanine and salts thereof.8. The suppository formulation according to claim 2 , where Rand Rare valine claim 2 , sarcosine claim 2 , leucine claim 2 , glutamine claim 2 , tryptophan claim 2 , tyrosine claim 2 , or alanine or a combination thereof claim 2 , and salts thereof.9. The suppository formulation according to claim 3 , where R claim 3 , Rand Rare valine claim 3 , sarcosine claim 3 , leucine claim 3 , glutamine claim 3 , tryptophan claim 3 , tyrosine claim 3 , or alanine or a combination thereof claim 3 , and salts thereof.11. The suppository formulation according to claim 10 , wherein A is the residue of one natural amino acid and salts thereof.12. The suppository formulation according to claim 10 , wherein A is the residue of two natural amino acids and salts thereof.13. The suppository ...

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Номер записи: 32
18-02-2021 дата публикации

PSMA-TARGETED NIR DYES AND THEIR USES

Номер: US20210046194A1
Автор: Kularatne Sumith A
Принадлежит:

The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing prostate specific membrane antigen (PSMA), such as prostate cancer and related diseases. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds. 1. A method of optical or diagnostic imaging of lung tissue that express prostate specific membrane antigen (PSMA) in a subject , wherein the lung tissue is selected from the group consisting of diseased lung tissue , abnormal lung tissue , lung tumor lesions , lymph nodes with metastatic lung tumor cells , primary lung cancer cells , and secondary lung cancer cells , the method comprising: [{'br': None, 'B—X—Y—Z wherein'}, 'B comprises a compound capable of binding to PSMA;', {'sub': '2', 'X is selected from the group consisting of polyethylene glycol (PEG), N-amino-dPEG-acid, and polyethylene amine (PEA);'}, 'Y comprises at least one amino acid, or a derivative thereof; and', 'Z comprises a near-infrared (NIR) dye;, '(a) contacting the lung tissue with a composition comprising a compound, or a pharmaceutically acceptable salt of the compound, wherein the compound has the formula(b) allowing time for the compound to distribute within the lung tissue;(c) illuminating the lung tissue with an excitation light of a wavelength absorbed by the compound; and(d) detecting the optical signal emitted by the compound in the lung tissue.2. The method of claim 1 , wherein B is selected from the group consisting of a small molecule claim 1 , ligand claim 1 , inhibitor claim 1 , agonist claim 1 , and a derivative thereof.3. The method of claim 1 , wherein B is 2-[3-(1 claim 1 ,3- ...

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Номер записи: 33
13-02-2020 дата публикации

Novel composition for organ preservation

Номер: US20200045954A1
Автор: Lindon Young, Robert Barsotti
Принадлежит: Individual

The present invention relates to a peptide and solutions for preservation, perfusion, and/or reperfusion of an organ, especially the heart, for transplantation or after coronary angioplasty/coronary arterial bypass. The peptide contains the amino acid sequence of the sequence Phe-D-Arg-Phe-Amide (SEQ ID NO: 1), and the solution contains the peptide dissolved therein.

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Номер записи: 34
13-02-2020 дата публикации

COMPOUNDS USEFUL FOR THE TREATMENT AND/OR CARE OF THE SKIN, HAIR, NAILS AND/OR MUCOUS MEMBRANES

Номер: US20200046625A1
Автор: Doménech Nuria Almiñana, Ferrer Montiel Antonio Vicente, Garcia Consuelo, Van Den Nest Wim
Принадлежит: LUBRIZOL ADVANCED MATERIALS, INC.

A peptide has the formula (I) R—W—X-AA-AA-AA-Y—Z—R, where AAis Tyr or Trp, AAis Val, Ile, Leu or Met, AAis Tyr, Phe or Trp, W, X, Y and Z are amino acids, m, n, p and q are each 0 or 1, and m+n+p+q is less than or equal to 2. Ris H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl, or R—CO—. Ris H, a non-cyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl or heteroarylalkyl. Ris —NRR, —OR, or —SR. Rand Rare each H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, or aralkyl. Rand Rare not amino acids. Cosmetic or pharmaceutical compositions may include the peptide. It find use in reduction of lipid accumulation in the skin, treatment of cellulite, and treatment of symptoms of skin aging. 1. A compound of formula (I):{'br': None, 'sub': 1', 'm', 'n', '1', '2', '3', 'p', 'q', '2, 'R—W—X-AA-AA-AA-Y—Z—R\u2003\u2003(I),'}its stereoisomers and/or its cosmetically or pharmaceutically acceptable salts, wherein:{'sub': '1', 'AAis selected from the group consisting of Tyr and Trp;'}{'sub': '2', 'AAis selected from the group consisting of Val, Ile, Leu and;'}{'sub': '3', 'AAis selected from the group consisting of Tyr, Phe and Trp;'}W, X, Y and Z are each independently an amino acid;m, n, p and q are each independently 0 or 1;m+n+p+q is less than or equal to 2;{'sub': 1', '5', '5, 'Ris selected from the group consisting of H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl and R—CO—, wherein Ris selected from the group consisting of H, a non-cyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl and heteroarylalkyl;'}{'sub': 2', '3', '4', '3', '3', '3', '4, 'Ris selected from the group consisting of —NRR, —OR, and —SR, wherein Rand Rare independently selected from a group consisting of H, a polymer derived from polyethylene ...

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Номер записи: 35
08-05-2014 дата публикации

Hepatitis C Virus Inhibitors

Номер: US20140127156A1
Автор: Gillis Eric P., Nagalakshim Pulicharla, Renduchintala Kishore V., Sarkunam Kandhasamy, Scola Paul Michael, Sun Li-Qiang, Zhao Qian
Принадлежит:

Hepatitis C virus inhibitors having the general formula (I) 2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein m and p are 1.3. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein is a double bond.4. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare hydrogen.5. A compound of wherein Ris selected from hydrogen and alkyl.12. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , whereinm and p are 1;{'img': {'@id': 'CUSTOM-CHARACTER-00020', '@he': '2.79mm', '@wi': '8.13mm', '@file': 'US20140127156A1-20140508-P00001.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, 'is a double bond;'}{'sup': y', 'z, 'Rand Rare hydrogen;'}{'sup': '2', 'and Ris selected from hydrogen and alkyl.'}16. A composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.17. The composition of further comprising at least one additional compound having anti-HCV activity.18. The composition of wherein at least one of the additional compounds is an interferon or a ribavirin.19. The composition of wherein the interferon is selected from interferon alpha 2B claim 18 , pegylated interferon alpha claim 18 , consensus interferon claim 18 , interferon alpha 2A claim 18 , and lymphoblastoid interferon tau.20. The composition of wherein at least one of the additional compounds is selected from interleukin 2 claim 17 , interleukin 6 claim 17 , interleukin 12 claim 17 , Imiquimod claim 17 , ribavirin claim 17 , an inosine 5′-monophosphate dehydrogenase inhibitor claim 17 , amantadine claim 17 , and rimantadine.21. The composition of wherein at least one of the additional compounds is effective to inhibit the function of a target selected from HCV metalloprotease claim 17 , HCV serine protease claim 17 , HCV polymerase claim 17 , HCV helicase ...

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Номер записи: 36
21-02-2019 дата публикации

FAP-ACTIVATED PROTEASOME INHIBITORS FOR TREATING SOLID TUMORS

Номер: US20190054181A1
Автор: Bachovchin William W., Lai Hung-sen, Poplawski Sarah E.
Принадлежит:

Disclosed are proteasome inhibitors, fibroblast activation protein (FAP)-activated prodrugs of proteasome inhibitors, and pharmaceutically acceptable salts of the inhibitors and prodrugs. Also disclosed are related pharmaceutical compositions, and methods of using the inhibitors and prodrugs and compositions thereof, for example, in treating cancer or other cell proliferative diseases. In vitro and in vivo methods of quantifying the expression of FAP in a biopsy sample and a mammal, respectively, are also disclosed. 153-. (canceled)5559-. (canceled)6179-. (canceled)81122-. (canceled)123. The method of claim 54 , wherein Ris methyl.124. The method of claim 54 , wherein Yand Yare OH.125. The method of claim 54 , wherein Ris iso-butyl.126. The method of claim 54 , wherein Ris H.128. The method of claim 60 , wherein Ris methyl.129. The method of claim 60 , wherein Yand Yare OH.130. The method of claim 60 , wherein Ris iso-butyl.131. The method of claim 60 , wherein Ris H.133. The method of claim 80 , wherein Ris methyl.134. The method of claim 80 , wherein Yand Yare OH.135. The method of claim 80 , wherein Ris iso-butyl.136. The method of claim 80 , wherein Ris H. This application is a Continuation of U.S. patent application Ser. No. 15/167,109, filed May 27, 2016, now U.S. Pat. No. 9,956,297, which is a Continuation of U.S. patent application Ser. No. 14/241,666, filed May 19, 2014, now U.S. Pat. No. 9,597,410, which is the U.S. national phase of International Patent Application No. PCT/US2012/053140, filed Aug. 30, 2012, which claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 61/528,824, filed Aug. 30, 2011.This invention was made with government support under grant CA156930 awarded by the National Institutes of Health. The government has certain rights in the invention.One in four deaths in the USA is due to cancer, the second leading cause of death after heart disease. Lung cancer is the leading cause of mortality among cancers, and the ...

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Номер записи: 37
01-03-2018 дата публикации

CARBAZOLE COMPOUND HAVING ANTI-VIRUS ACTIVITY

Номер: US20180057527A1
Автор: JANG Sung Key, KEUM Gyo Chang, KIM Eunice Eun Kyeong, KIM HEE SUN, KWAK Jin Sook, Li Hua, PAE Ae Nim, PARK Jin Hyeong
Принадлежит:

The present invention relates to a carbazole compound having anti-virus activity, and more particularly, to a novel compound selected from the group of consisting of a carbazole compound which shows excellent anti-proliferative efficacy against hepatitis C virus (HCV), a pharmaceutically acceptable salt thereof, a hydrate thereof, and an isomer thereof; an anti-virus pharmaceutical composition including the novel compound as an active ingredient; a pharmaceutical composition for preventing or treating liver diseases caused by hepatitis C virus; and a method of preparing the novel compound. 6. The compound of claim 1 , wherein the compound is selected from (Compound No. 1) dimethyl ((1R claim 1 ,1′R)-((2S claim 1 ,2′S)-(((9-butyl-9H-carbazole-2 claim 1 ,7-diyl)bis(azanediyl))bis(carbonyl))bis(pyrrolidine-2 claim 1 ,1-diyl))bis(2-oxo-1-phenylethane-2 claim 1 ,1-diyl))dicarbamate claim 1 ,(Compound No. 2) dimethyl ((2R,2′R)-((2S,2′S)-(((9-butyl-9H-carbazole-2,7-diyl)bis(azanediyl))bis(carbonyl))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-1,2-diyl))dicarbamate,(Compound No. 3) dimethyl ((1S,1′S)-((2S,2′S)-(((9-butyl-9H-carbazole-2,7-diyl)bis(azanediyl))bis(carbonyl))bis(pyrrolidine-2,1-diyl))bis(2-oxo-1-phenylethane-2,1-diyl))dicarbamate,(Compound No. 4) dimethyl ((2S,2′S)-((2S,2′S)-(((9-butyl-9H-carbazole-2,7-diyl)bis(azanediyl))bis(carbonyl))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-1,2-diyl))dicarbamate,(Compound No. 5) (2S,2′S)—N,N′-(9-butyl-9H-carbazole-2,7-diyl)bis(1-((S)-3-methyl-3-2-(2-oxooxazolidine-3-yl)butanoyl)pyrrolidine-2-carboxamide),(Compound No. 6) dimethyl ((1R,1′R)-((2S,2′S)-(((9-butyl-9H-carbazole-2,7-diyl)bis(azanediyl))bis(carbonyl))bis(pyrrolidine-2,1-diyl))bis(2-oxo-1-phenylethane-2,1-diyl))dicarbamate,(Compound No. 7) dimethyl ((2R,2′R)-((2S,2′S)-(((9-methyl-9H-carbazole-2,7-diyl)bis(azanediyl))bis(carbonyl))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-1,2-diyl))dicarbamate,(Compound No. 8) dimethyl ((1S,1′S)-((2S,2′S)-(((9 ...

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Номер записи: 38
01-03-2018 дата публикации

INDOLINE COMPOUNDS AS GRANZYME B INHIBITORS

Номер: US20180057528A1
Автор: Cameron Dale R.
Принадлежит: viDA Therapeutics Inc.

Granzyme B inhibitor compounds, compositions that include the compounds, and methods for using the compounds. The compounds of the invention have advantageous water solubility and effectively inhibit Granzyme B. 811-. (canceled)12. A pharmaceutical composition claim 1 , comprising a compound of and a pharmaceutically acceptable carrier.13. A method for inhibiting Granzyme B in a subject claim 1 , comprising administering an effective amount of a compound of to a subject in need thereof.14. A method for treating a disease claim 1 , disorder claim 1 , or condition treatable by inhibiting Granzyme B claim 1 , comprising administering a therapeutically effective amount of a compound of to a subject in need thereof.15. The method of claim 14 , wherein the disease claim 14 , disorder claim 14 , or condition treatable by inhibiting Granzyme B is selected from treating dissection claim 14 , aneurysm claim 14 , and atherosclerosis.16. The method of claim 14 , wherein the condition treatable by inhibiting Granzyme B is a wound and administering the compound or composition promotes wound healing.17. The method of claim 13 , wherein administering the compound comprises topical administration claim 13 , oral administration claim 13 , and administration by injection. This application is a continuation of U.S. patent application Ser. No. 14/869,750, filed Sep. 29, 2015 (now U.S. Pat. No. 9,605,021), which is a continuation-in-part of International Application No. PCT/CA2014/050317, filed Mar. 28, 2014, which claims the benefit of U.S. Patent Application No. 61/806,767, filed Mar. 29, 2013, and U.S. Patent Application No. 61/941,358, filed Feb. 18, 2014, and is a continuation-in-part of International Application No. PCT/CA2014/050318, filed Mar. 28, 2014, which claims the benefit of U.S. Patent Application No. 61/806,767, filed Mar. 29, 2013, and U.S. Patent Application No. 61/941,358, filed Feb. 18, 2014, each expressly incorporated herein by reference in its entirety.The present ...

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Номер записи: 39
04-03-2021 дата публикации

PEPTIDE-COMPOUND CYCLIZATION METHOD

Номер: US20210061860A1
Автор: Asou Kousuke, Emura Takashi, Hisada Nozomi, Ilda Takeo, Ilkura Hitoshi, Kariyuki Shiori, Kato Tatsuya, Kimura Kaori, Kojima Miki, Kojima Tetsuo, MATSUO Atsushi, Murao Naoaki, NAKANO Kazuhiko, OHTA Atsushi, SHIRAISHI Takuya, Takano Koji, Takano Ryusuke, Takeyama Ryuichi, Tanada Mikimasa, Torizawa Takuya, Yamagishi Yusuke
Принадлежит: Chugai Seiyaku Kabushiki Kaisha

An object of the present invention is to provide methods of discovering drugs effective for tough targets, which have conventionally been discovered only with difficulty. The present invention relates to novel methods for cyclizing peptide compounds, and novel peptide compounds and libraries comprising the same, to achieve the above object. 138.-. (canceled)39. A peptide compound having a cyclic portion , wherein:(i) the peptide compound contains a cyclic portion composed of 5 to 12 amino acids and amino acid analog residues in total, and has 9 to 13 amino acids and amino acid analogs in total,(ii) the peptide compound contains at least two N alkylated amino acids,(iii) the peptide compound has a C log P value of 6 or more, and(iv) the peptide compound has at least one amide bond formed between a side chain of an amino acid or an amino acid analog and a nitrogen atom of the main chain of another amino acid or amino acid analog.40. (canceled)41. The peptide compound according to claim 39 , wherein the compound further comprises at least one linear portion composed of 1 to 8 amino acids and amino acid analog residues in total.42. The peptide compound according to claim 39 , wherein the C-terminal site of the peptide is —CO—NRR′ whereinR and R′ each independently represent a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted cycloalkyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, or an optionally substituted aralkyl group, orR and R′ form a ring.4454.-. (canceled)55. The peptide compound according to claim 41 , wherein the C-terminal site of the peptide is —CO—NRR′ whereinR and R′ each independently represent a hydrogen atom, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted cycloalkyl group, an optionally substituted ...

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Номер записи: 40
05-03-2015 дата публикации

AROMATIC-CATIONIC PEPTIDES AND USES OF SAME

Номер: US20150065437A1
Автор: Gu Lawrence, Liu Liping
Принадлежит: Stealth Peptides International, Inc.

The disclosure provides compositions and methods relating to aromatic-cationic peptides. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof. For example, the peptides may be administered to subjects in need of a mitochondrial-targeted antioxidant. 1. An aromatic-cationic peptide selected from the group consisting of:{'sub': '2', 'D-Arg-Tyr-Lys-Phe-NH'}{'sub': '2', 'D-Arg-Dmt-D-Lys-Phe-NH'}{'sub': '2', 'D-Arg-Dmt-Lys-D-Phe-NH'}{'sub': '2', 'Phe-D-Arg-D-Phe-Lys-NH'}{'sub': '2', 'Phe-D-Arg-Phe-D-Lys-NH'}{'sub': '2', 'D-Phe-D-Arg-D-Phe-D-Lys-NH'}{'sub': '2', 'Lys-D-Phe-Arg-Dmt-NH'}{'sub': '2', 'D-Arg-Arg-Dmt-Phe-NH'}{'sub': '2', 'Dmt-D-Phe-Arg-Lys-NH'}{'sub': '2', 'Phe-D-Dmt-Arg-Lys-NH'}{'sub': '2', 'D-Arg-Dmt-Lys-NH'}{'sub': '2', 'Arg-D-Dmt-Lys-NH'}{'sub': '2', 'D-Arg-Dmt-Phe-NH'}{'sub': '2', 'Arg-D-Dmt-Arg-NH'}{'sub': '2', 'Dmt-D-Arg-NH'}{'sub': '2', 'D-Arg-Dmt-NH'}{'sub': '2', 'D-Dmt-Arg-NH'}{'sub': '2', 'Arg-D-Dmt-NH'}{'sub': '2', 'D-Arg-D-Dmt-NH'}{'sub': '2', 'D-Arg-D-Tyr-Lys-Phe-NH'}{'sub': '2', 'D-Arg-Tyr-D-Lys-Phe-NH'}{'sub': '2', 'D-Arg-Tyr-Lys-D-Phe-NH'}{'sub': '2', 'D-Arg-D-Tyr-D-Lys-D-Phe-NH'}{'sub': '2', 'Lys-D-Phe-Arg-Tyr-NH'}{'sub': '2', 'D-Arg-Arg-Tyr-Phe-NH'}{'sub': '2', 'Tyr-D-Phe-Arg-Lys-NH'}{'sub': '2', 'Phe-D-Tyr-Arg-Lys-NH'}{'sub': '2', 'D-Arg-Tyr-Lys-NH'}{'sub': '2', 'Arg-D-Tyr-Lys-NH'}{'sub': '2', 'D-Arg-Tyr-Phe-NH'}{'sub': '2', 'Arg-D-Tyr-Arg-NH'}{'sub': '2', 'Tyr-D-Arg-NH'}{'sub': '2', 'D-Arg-Tyr-NH'}{'sub': '2', 'D-Tyr-Arg-NH'}{'sub': '2', 'Arg-D-Tyr-NH'}{'sub': '2', 'D-Arg-D-Tyr-NH'}{'sub': '2', 'Dmt-Lys-Phe-NH'}{'sub': '2', 'Lys-Dmt-D-Arg-NH'}{'sub': '2', 'Phe-Lys-Dmt-NH'}{'sub': '2', 'D-Arg-Phe-Lys-NH'}{'sub': '2', 'D-Arg-Cha-Lys-NH'}{'sub': '2', 'D-Arg-Trp-Lys-NH'}{'sub': '2', 'Dmt-Lys-D-Phe-NH'}{'sub': '2', 'Dmt-Lys-NH'}{'sub': '2', 'Lys-Phe-NH'}{'sub': '2', 'D-Arg-Cha-Lys-Cha-NH'}{'sub': '2', 'D-Nle-Dmt-Ahe-Phe-NH'}{'sub': '2', 'D-Nle-Cha-Ahe-Cha-NH'}wherein ...

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Номер записи: 41
27-02-2020 дата публикации

AZAINDOLINE COMPOUNDS AS GRANZYME B INHIBITORS

Номер: US20200062803A1
Автор: Cameron Dale R.
Принадлежит: viDA Therapeutics Inc.

Azaindoline compounds as granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Methods for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided. 6. The compound of claim 5 , its stereoisomers claim 5 , tautomers claim 5 , and pharmaceutically acceptable salts thereof claim 5 , wherein:{'sub': 10', '1', '12, 'R, when defined as C-Calkyl substituted with a carboxylic acid or carboxylate group, is{'sub': 2', 'n', '2, '—(CH)—COH, where n is 2, 3, 4, 5, or 6;'}{'sub': 1', '3', '6', '10, 'optionally wherein one or more single methylene carbons are substituted with a fluoro, hydroxy, amino, C-Calkyl, or C-Caryl group;'}{'sub': 1', '3, 'optionally wherein one or more single methylene carbons are substituted with two fluoro or C-Calkyl groups;'}optionally wherein one or more single methylene carbons are substituted with two alkyl groups that taken together with the carbon to which they are attached form a 3, 4, 5, or 6-membered carbocyclic ring; andoptionally wherein adjacent carbon atoms from an unsaturated carbon-carbon bond or taken form a benzene ring; or8. The compound of claim 5 , its stereoisomers claim 5 , tautomers claim 5 , and pharmaceutically acceptable salts thereof claim 5 , wherein:{'sub': '1', 'Ris tetrazole or triazole;'}{'sub': 3', '1', '4', '1', '4, 'Ris hydrogen; C-Calkyl optionally substituted with a carboxylic acid, carboxylate, or a carboxylate ester group; or C-Calkyl optionally substituted with an amide, which may be optionally substituted with an alkylheteroaryl group;'}{'sub': 4', '1', '12', '3', '6', '6', '10', '3', '10, 'Ris C-Calkyl, C-Ccycloalkyl, C-Caryl, C-Cheteroaryl, or heterocyclyl; and'}{'sub': 10', '1', '12', '6', '10', '1', '10, 'Ris C-Calkyl optionally substituted with C-Caryl, C-Cheteroaryl, amino, or carboxylic acid.'}11. The compound of claim 10 , its stereoisomers claim 10 , tautomers claim 10 , and ...

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Номер записи: 42
16-03-2017 дата публикации

PRO-PIGMENTING PEPTIDES

Номер: US20170071844A1
Автор: Mondon Philippe, Peschard Olivier
Принадлежит: SEDERMA

The invention is directed to the use of at least one peptide of formula: X-(Xaa)-Pro*-(Xaa)-Y (I) With: —n=0, 1 or 2; -m=0 or 1 and if m=0 then n≠0-Xaais: -An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; —A polar aminoacid selected from Serine (Ser, S), Threonine (Thr, T), Tyrosine (Tyr, Y), Asparagine (Asn, N), Glutamine (Gln, Q) and analogues and derivatives thereof; —or Glycine (Gly, G); When n=2 the two aminoacids Xaacan be the same or different; -Xaais: —An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; —A basic aminoacid selected from Arginine (Arg, R), Lysine (Lys, K) and Histidine (His, H) and analogues and derivatives thereof; —Glycine (Gly, G) or Serine (Ser, S); —At the N terminal end of the peptide, X is selected from H, —CO—Rand —SO—R; —At the C terminal end of the peptide, Y is selected from OH, OR, NH, NHRor NRR, Rand Rbeing independantly from each other, selected from an alkyle, aryle, aralkyle, alkylaryl, alkoxy and aryloxy group, that can be linear, branched, cyclic, poly-cyclic, non-saturated, hydroxylated, carbonylated, phosphorylated and/or sulphured, with the possibility to have in said group skeleton a O, S and/or N heteroatom; -Pro* corresponding to a Proline, an analogue or derivative thereof; Excluding the peptides where X═H and Y═OH, for a non therapeutical cosmetic pro-pigmenting treatment of skin. The invention also encompasses new tripeptides of formula (I) suitable for a non therapeutical cosmetic treatment of skin. 153-. (canceled)54. A method of stimulating collagen synthesis in skin of a subject in need thereof comprising topically applying to the skin of said subject at least one peptide selected from the ...

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Номер записи: 43
17-03-2016 дата публикации

Synthetic anti-inflammatory peptides and use thereof

Номер: US20160075737A1
Автор: Amiram Ariel, Aviv Lutaty
Принадлежит: CARMEL-HAIFA UNIVERSITY ECONOMIC CORP

The present invention is directed to synthetic anti-inflammatory peptides and use thereof in the treatment and prevention of inflammatory and fibrotic conditions. Specifically, the invention relates in some embodiments to short isolated peptides having the amino acid sequence Phe-Lys-Glu (FKE), Tyr-Lys-Glu (YKE) or comprising a plurality of these sequences that may be flanked by Ala/Gly (A/G) linkers. The invention further relates in some embodiments to methods for inhibiting scar formation and for treating and alleviating IL-10 dependent conditions.

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Номер записи: 44
24-03-2022 дата публикации

TRANSFECTION COMPLEXES AND METHODS OF USING THE SAME

Номер: US20220090141A1
Автор: Gebeyehu Gulilat, JESSEE Joel
Принадлежит:

Disclosed herein are transfection complexes comprising at least one cell surface ligand; at least one helper lipid component; and a transfection enhancer. Also disclosed are pharmaceutical compositions comprising the disclosed transfection complexes, and a pharmaceutically acceptable carrier. Further, disclosed are methods of transfecting a cell, the method comprising the steps of: obtaining a transfection complex as disclosed; and contacting a cell with the transfection complex. 1. A transfection complex comprising a transfection enhancer and a cell surface ligand.2. The transfection complex of claim 1 , wherein the transfection enhancer is:i) a peptide;ii) an amphipathic peptide;iii) a fusion peptide;iv) selected from the group consisting of SEQ ID NOs:1-505;v) selected from the group consisting of SEQ ID NOs:107, 205, 216, 218, 219, 220, 224, 226, 229, 230, 234, 236, 236, 237, 238, 239, 256, 268, 323, 326, 327, 328, 332, 335, 336, 338, 341, 342, 343, 344, 345, 347, 348, 349, 350, 351, 352, 353, 354, 355, 357, 358, 359, 360, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 450, 452, 454, and 503;vi) selected from the group consisting of SEQ ID NOs:205, 237, 268, 326, 328, 335, 336, 342, 347, 348, 352, 353, 355, 357, 358, 365, 367, 377, 379, 381, 450, 454, and 503;vii) selected from the group consisting of SEQ ID NOs:205, 216, 218, 219, 220, 224, 226, 229, 230, 234, 236, 236, 237, 238, 239, 256, 268, 323, 326, 327, 328, 332, 336, 338, 341, 342, 343, 344, 345, 347, 348, 349, 350, 351, 352, 353, 354, 355, 357, 358, 359, 360, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 450, 452, 454, and 503;viii) selected from the group consisting of SEQ ID NOs:236, 358, and 373;ix) selected from the group consisting of SEQ ID NOs:107, 205, 216, 218, 219, 220, 224, 226, 229, 230, 234, 236, 236, 237, 238, 239, 256, 268, 323, 326, 327, 328, 332, 335, 336, 338, 341, 342, 343, 344, 345, 347, 348, 349, 350, 351, 352, 353, 354, 355, 357, 358, 359, 360, 361, 363, ...

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Номер записи: 45
05-03-2020 дата публикации

THERAPEUTIC PEPTIDES

Номер: US20200071355A1
Автор: KIMURA Saeko, Ohinata Kousaku, SUZUKI Hideyuki
Принадлежит:

The present invention provides peptides, salts thereof, peptide conjugates, and salts thereof having an anxiolytic-like effect, for example a peptide comprising any amino acid sequence selected from (i) an amino acid sequence SYLPPLTT (SEQ ID NO: 1), (ii) an amino acid sequence YHIEPV (SEQ ID NO: 2), (iii) an amino acid sequence YLLVK (SEQ ID NO: 3), (iv) an amino acid sequence SYLPPLT (SEQ ID NO: 4), (v) an amino acid sequence FLLVK (SEQ ID NO: 5), and (vi) an amino acid sequence WLLVK (SEQ ID NO: 6). 1. A compound that is a peptide or a salt thereof , wherein the peptide:(a) is 3 to 20 amino acids in length;{'sub': 1', '2', '3, 'claim-text': [{'sub': '1', '(i) Xis a hydrophobic amino acid,'}, {'sub': 2', '3, '(ii) Xand Xare each independently selected from any amino acid;'}], '(b) has an amino acid sequence comprising at least 3 consecutive amino acids from the N-terminal or C-terminal end of the amino acid sequence XLXXVK (SEQ ID NO:8), wherein'}(c) has a hydrophobic N-terminal amino acid; and{'sub': 4', '5', '4', '5', '4', '5, '(d) does not consist of the amino acid sequence YLLVR (SEQ ID NO:13), XLX(SEQ ID NO:30), XLXEIAR (SEQ ID NO:31), VYLPR (SEQ ID NO:32), YLPR (SEQ ID NO:33), or VLQRF (SEQ ID NO:34), where Xis Y, F, W, or H and Xis Y, F, W, Q, or L.'}2. The compound of claim 1 , wherein Xis an aromatic amino acid.3. The compound of claim 1 , wherein Xis Y claim 1 , F claim 1 , W claim 1 , A claim 1 , I claim 1 , L claim 1 , V claim 1 , or M.4. The compound of claim 1 , wherein Xis Y claim 1 , F claim 1 , or W.5. The compound of claim 1 , wherein Xand/or Xis L claim 1 , I claim 1 , V claim 1 , or A.6. The compound of claim 1 , wherein the peptide comprises the amino acid sequence:{'sub': 1', '2, '(a) XLX(SEQ ID NO:15);'}{'sub': '3', '(b) XVK (SEQ ID NO:16);'}(c) YLL (SEQ ID NO:7);(d) LVK (SEQ ID NO:9);{'sub': 1', '2', '3, '(e) XLXX(SEQ ID NO:17);'}{'sub': 1', '2', '3, '(f) XLXXK (SEQ ID NO:29);'}{'sub': 2', '3, '(g) XXVK (SEQ ID NO:18);'}(h) YLLV (SEQ ID NO: ...

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Номер записи: 46
05-03-2020 дата публикации

COMPOUNDS FOR PROTEASOME

Номер: US20200071356A1
Автор: LAIDIG Guy J., SMYTH Mark S.
Принадлежит:

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. 2. A compound of claim 1 , wherein X is O.3. A compound of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , and Rare independently selected from Calkyl claim 2 , Chydroxyalkyl claim 2 , and Caralkyl; and Ris hydrogen.4. A compound of claim 3 , wherein Rand Rare independently Caralkyl and Rand Rare independently Calkyl.5. A compound of claim 4 , wherein R claim 4 , R claim 4 , R claim 4 , and Rare all hydrogen.6. A compound of claim 5 , wherein Y is selected from N-alkyl claim 5 , O claim 5 , and CH.7. A compound of claim 6 , wherein Z is CH claim 6 , and m and n are both 0.8. A compound of claim 6 , wherein Z is CH claim 6 , m is 0 claim 6 , and n is 2 or 3.9. A compound of claim 6 , wherein Z is O claim 6 , m is 1 claim 6 , and n is 2.17. A compound of claim 16 , wherein X is O.18. A compound of claim 17 , wherein R claim 17 , R claim 17 , R claim 17 , and Rare independently selected from Calkyl claim 17 , Chydroxyalkyl claim 17 , and Caralkyl.19. A compound of claim 18 , wherein Rand Rare independently Caralkyl and Rand Rare independently Calkyl.21. A compound of claim 20 , wherein X is O.22. A compound of claim 21 , wherein Rand Rare independently selected from Calkyl claim 21 , Chydroxyalkyl claim 21 , and Caralkyl.23. A compound of claim 22 , wherein Rand Rare independently Calkyl.24. A compound ...

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Номер записи: 47
30-03-2017 дата публикации

Biologically active C-terminal arginine-containing peptides

Номер: US20170088813A1
Автор: Breece Tim, Shiratori Masaru Ken, Wilkins James
Принадлежит:

The present invention concerns the separation, identification and characterization of active peptide fragments from peptones. 123-. (canceled)24. A culture medium comprising an isolated C-terminal arginine-containing di- or tri-peptide selected from:a) the tripeptides EVR, DPR, TVR, EIR, ELR, INR, LNR, QVR, AVR, GIR, GLR, IVR, LVR, ITR, LTR, DTR, ESR, GGR, DVR, ILR, LLR, AIR, ALR, ADR, AGR, DQR, ENR, DMR, EMR, GTR, FPR, LMR, IPR, and LPR;b) the tripeptides EVR, VER, LTR, TLR, ITR, TIR, TVR, and VTR; andc) the dipeptides DR, VR, ER, NR, and QR, wherein said peptide exhibits a peptone biological activity.25. The culture medium of claim 24 , wherein said peptide is obtained by fractionation of a peptone or is chemically synthesized.26. The culture medium of wherein said peptide is selected from the peptides EVR claim 24 , DPR claim 24 , TVR claim 24 , EIR claim 24 , ELR claim 24 , INR claim 24 , LNR claim 24 , QVR claim 24 , AVR claim 24 , GIR claim 24 , GLR claim 24 , IVR claim 24 , LVR claim 24 , ITR claim 24 , LTR claim 24 , DTR claim 24 , ESR claim 24 , GGR claim 24 , DVR claim 24 , ILR claim 24 , LLR claim 24 , AIR claim 24 , ALR claim 24 , ADR claim 24 , AGR claim 24 , DQR claim 24 , ENR claim 24 , DMR claim 24 , EMR claim 24 , GTR claim 24 , FPR claim 24 , LMR claim 24 , IPR claim 24 , LPR claim 24 , DR claim 24 , VR claim 24 , ER claim 24 , NR claim 24 , and QR.27. The culture medium of wherein said peptide is a tripeptide.28. The culture medium of wherein said tripeptide is selected from the peptides EVR claim 27 , DPR claim 27 , TVR claim 27 , EIR claim 27 , ELR claim 27 , INR claim 27 , LNR claim 27 , QVR claim 27 , AVR claim 27 , GIR claim 27 , GLR claim 27 , IVR claim 27 , LVR claim 27 , ITR claim 27 , LTR claim 27 , DTR claim 27 , ESR claim 27 , GGR claim 27 , DVR claim 27 , ILR claim 27 , LLR claim 27 , AIR claim 27 , ALR claim 27 , ADR claim 27 , AGR claim 27 , DQR claim 27 , ENR claim 27 , DMR claim 27 , EMR claim 27 , GTR claim 27 , FPR claim 27 , LMR ...

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Номер записи: 48
09-04-2015 дата публикации

FPR1 ANTAGONIST DERIVATIVES AND USE THEREOF

Номер: US20150099691A1
Автор: HSIEH PEI-WEN, Huang Yin-Ting, Hung Chih-Hao, Hwang Tsong-Long
Принадлежит: CHANG GUNG UNIVERSITY

A dipeptide derivative as formyl peptide receptor 1 (FPR1) antagonist is provided. The dipeptide derivative is represented by formula (I), 2. The method as claimed in claim 1 , further comprising providing one selected from a group consisting of a pharmaceutically acceptable salt claim 1 , solvate and combination thereof for formula (I).3. The method as claimed in claim 1 , wherein the neutrophil inflammatory disorders are selected from a group consisting of lung injury claim 1 , chronic obstructive pulmonary disease claim 1 , acute respiratory distress syndrome claim 1 , asthma claim 1 , ischemic reperfusing injury claim 1 , arthritis and septicemia.5. The dipeptide derivative as claimed in claim 4 , wherein the halogen is one selected from a group consisting of fluorine (F) claim 4 , chlorine (Cl) claim 4 , bromine (Br) and iodine (I).6. The dipeptide derivative as claimed in inhibits and antagonizes a formyl peptide receptor 1.8. The dipeptide derivative as claimed in inhibits and antagonizes a formyl peptide receptor 1.9. The dipeptide derivative as claimed in inhibits at least one selected from a group consisting of FPR1 downstream claim 8 , calcium claim 8 , mitogen-activated protein kinases and protein kinase B.10. The dipeptide derivative as claimed in claim 8 , wherein the dipeptide derivative competitively inhibits superoxide anion generation and neutrophil elastase release induced by a FPR1 activator.11. The dipeptide derivative as claimed in claim 10 , wherein the FPR1 activator is derived from neutrophil inflammatory disorders and the neutrophil inflammatory disorder is selected from a group consisting of following diseases or symptoms: lung injury claim 10 , chronic obstructive pulmonary disease claim 10 , acute respiratory distress syndrome claim 10 , asthma claim 10 , ischemic reperfusing injury claim 10 , arthritis and septicemia. This application claims the benefit of Taiwan Patent Application No. 102136641, filed on Oct. 9, 2013, at the Taiwan ...

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Номер записи: 49
01-04-2021 дата публикации

MODIFIED PEPTIDES FOR USE IN TREATING NEURODEGENERATIVE DISORDERS

Номер: US20210094983A1
Автор: COSANO Roger Prades, GARCIA-RATES Sara, Greenfield Susan, MORAL Jesus Seco
Принадлежит:

The invention relates to neurodegenerative disorders, and in particular to novel peptides, peptidomimetics, compositions, therapies and methods for treating such conditions, for example Alzheimer's disease. 4. The method according to claim 1 , wherein Ris —NRR claim 1 , and is optionally —NH.7. (canceled)8. The method according to claim 1 , wherein Ris methyl or H.11. (canceled)12. The method according to claim 1 , wherein Ris methyl or —H.14. (canceled)16. (canceled)17. (canceled)18. The method according to claim 1 , wherein Ris methyl or H.22. (canceled)23. The method according to claim 1 , wherein the neurodegenerative disorder which is treated is one which is characterised by the damage or death of ‘Global’ neurons.24. The method according to claim 1 , wherein the neurodegenerative disorder is selected from a group consisting of Alzheimer's disease; Parkinson's disease; Huntington's disease; Motor Neurone disease; Spinocerebellar type 1 claim 1 , type 2 claim 1 , and type 3; Amyotrophic Lateral Sclerosis (ALS); schizophrenia; Lewy-body dementia; and Frontotemporal Dementia.2629-. (canceled)31. (canceled) The invention relates to neurodegenerative disorders, and in particular to novel peptides, peptidomimetics, compositions, therapies and methods for treating such conditions, for example Alzheimer's disease.The inventors have previously proposed that the neurodegenerative process is an aberrantly activated process of development. In support of this hypothesis, a hyper-trophy of the brainstem ‘hub’ neurons has actually been reported in Alzheimer brains (Bowser et al., 1997, Brain Pathol. 7:723-30). If large areas of this hub are damaged, then more than one neurodegenerative disease will present, as occurs in the frequently seen but never as yet explained cases of co-pathology with Alzheimer's and Parkinson's diseases. Interestingly, all the neurons within the vulnerable hub of Global neurons, despite transmitter heterogeneity, all contain the familiar enzyme ...

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Номер записи: 50
14-04-2016 дата публикации

INHIBITORS OF IAP

Номер: US20160102119A1
Автор: Cohen Frederick, Flygare John A., Gazzard Lewis J., Tsui Vickie Hsiao-Wei
Принадлежит: Genentech, Inc.

Novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies and have the general formula I: 2. The compound of which is (S)-1-[(S)-2-cyclohexyl-2-((S)-2-methylamino-propionylamino)-acetyl]-pyrrolidine-2-carboxylic acid (2-oxazol-2-yl-4-phenyl-thiazol-5-yl)-amide (Ia) or a pharmaceutically acceptable salt thereof.3. A compound of wherein R-Rare each independently H or methyl.4. A compound of wherein Ris cyclohexyl.5. A compound of wherein Ris cyclohexyl.6. A compound of wherein one of Rand Ris H and the other is methyl; or Ris methyl; or Rand Rare each H.7. A method for inhibiting the binding of an TAP protein to a caspase protein comprising contacting said TAP protein with a compound of .8. A method for treating a disease or condition associated with the overexpression of an TAP in a mammal claim 1 , comprising administering to said mammal an effective amount of a compound of .9. A method of inducing apoptosis in a cell comprising introducing into said cell a compound of .10. A method of sensitizing a cell to an apoptotic signal comprising introducing into said cell a compound of .11. The method of claim 10 , wherein said apoptotic signal is induced by contacting said cell with a compound selected from the group consisting of cytarabine claim 10 , fludarabine claim 10 , 5-fluoro-2′-deoxyuiridine claim 10 , gemcitabine claim 10 , methotrexate claim 10 , bleomycin claim 10 , cisplatin claim 10 , cyclophosphamide claim 10 , adriamycin (doxorubicin) claim 10 , mitoxantrone claim 10 , camptothecin claim 10 , topotecan claim 10 , colcemid claim 10 , colchicine claim 10 , paclitaxel claim 10 , vinblastine claim 10 , vincristine claim 10 , tamoxifen claim 10 , finasteride claim 10 , docetaxel and mitomycin C.12. The method of claim 10 , wherein said apoptotic signal is induced by contacting said cell with Apo2L/TRAIL.13. A method for treating cancer claim 1 , comprising administering to said mammal an effective amount of a compound of .14. A ...

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Номер записи: 51
20-04-2017 дата публикации

AMIDE COMPOUND

Номер: US20170107240A1
Автор: Fukase Yoshiyuki, Fukumoto Shoji, Ishii Naoki, Kono Mitsunori, Ochida Atsuko, Oda Tsuneo, Sasaki Yusuke, Sato Ayumu, SHIRAI Junya, Tokuhara Hidekazu, Tomata Yoshihide, YAMAMOTO Satoshi
Принадлежит:

The present invention relates to compound (I) or a salt thereof which has a RORγt inhibitory action. In the formula (I), each symbol is as defined in the specification. 2. The compound or salt of claim 1 , wherein the substituent that Ring A optionally further has is a fluorine atom or a chlorine atom.3. The compound or salt of claim 1 , wherein Ris a tert-butyl group claim 1 , a neopentyl group or a trimethylsilyl group.5. The compound or salt of claim 1 , wherein Ris a hydrogen atom or a methyl group.6. The compound or salt of claim 1 , wherein Ris (1) an optionally substituted 5-membered heterocyclic group claim 1 , (2) an optionally substituted 6-membered non-aromatic heterocyclic group claim 1 , (3) an optionally substituted 4-membered non-aromatic heterocyclic group claim 1 , (4) an optionally substituted Ccycloalkyl group claim 1 , or (5) an optionally substituted Calkyl group.7. (3S)—N-((1R)-2-((4-tert-Butyl-3-fluorophenyl)amino)-1-(4 claim 1 ,4-difluorocyclohexyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide or a salt thereof.8. N-((1R)-2-((3 claim 1 ,5-Difluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methyl-1 claim 1 ,2-oxazole-5-carboxamide or a salt thereof.9. (2R)—N-(4-tert-Butyl-3 claim 1 ,5-difluorophenyl)-2-(((3-hydroxy-1 claim 1 ,2-oxazol-5-yl)acetyl)amino)-2-(1-methyl-1H-indazol-5-yl)acetamide or a salt thereof.10. A medicament comprising the compound or salt of . The present invention relates to a heterocyclic compound having an RORγt inhibitory action, a medicament containing the compound, and the like.Th17 cell and inflammatory cytokine (IL-17A, IL-17F, etc.) produced thereby cause a decrease in QOL as a severe etiology cell and factor accompanying enhancement of a systemic new immune response, in various autoimmune disease such as inflammatory bowel disease (IBD), rheumatoid arthritis, multiple sclerosis or psoriasis. However, the existing therapeutic drugs show only limited effects, and therefore, the earliest ...

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Номер записи: 52
11-04-2019 дата публикации

AROMATIC-CATIONIC PEPTIDES AND USES OF SAME

Номер: US20190106458A1
Автор: Gu Lawrence, Liu Liping
Принадлежит:

The disclosure provides compositions and methods relating to aromatic-cationic peptides. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof For example, the peptides may be administered to subjects in need of a mitochondrial-targeted antioxidant. 2. A pharmaceutical composition comprising one or more aromatic-cationic peptides of and pharmaceutically acceptable salts thereof.3. The pharmaceutical composition of further comprising a pharmaceutically acceptable carrier.4. A method of reducing the number of mitochondria undergoing mitochondrial permeability transition (MPT) claim 1 , or preventing mitochondrial permeability transitioning in a mammal in need thereof claim 1 , the method comprising administering to the mammal an effective amount of one or more aromatic-cationic peptides of .5. A method for reducing oxidative damage in a mammal in need thereof claim 1 , the method comprising administering to the mammal an effective amount of one or more aromatic-cationic peptides of .6. A method for increasing the ATP synthesis rate in a mammal in need thereof claim 1 , the method comprising administering to the mammal an effective amount of one or more aromatic-cationic peptides of .8. The method of claim 7 , wherein detecting is performed during administration of the peptide.9. The method of claim 7 , wherein detecting is performed after administration of the peptide.10. The method of any one of claim 7 , wherein detecting comprises HPLC.11. The method of claim 10 , wherein the HPLC comprises reverse phase HPLC.12. The method of claim 10 , wherein the HPLC comprises ion exchange HPLC.13. The method of claim 7 , wherein detecting comprises mass spectrometry.14. The method of claim 7 , wherein the biological sample comprises a fluid.15. The method of claim 7 , wherein the biological sample comprises a cell.16. The method of claim 7 , wherein the biological sample comprises a tissue.17. The ...

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Номер записи: 53
28-04-2016 дата публикации

SELF-ASSEMBLED MICRO-AND NANOSTRUCTURES

Номер: US20160115196A1
Автор: ADLER-ABRAMOVICH Lihi, FICHMAN Galit, Gazit Ehud, Messersmith Phillip B.
Принадлежит: Ramot at Tel-Aviv University Ltd.

The present invention discloses self-assembled bioadhesive anti-microbial, anti-fouling and/or anti-oxidant micro- and nano-structures comprising a plurality of amino acids or peptides, wherein each amino acid is an aromatic amino acid comprising a catecholic moiety, and/or each peptide comprises at least one aromatic amino acid comprising a catecholic moiety. Further disclosed are methods and kits for preparing these micro- and nano-structures. Further disclosed are uses of these micro- and nano-structures in pharmaceutical, cosmetic and medical devices applications. 141-. (canceled)42. A self-assembled micro- or nano-structure comprising (i) a plurality of aromatic amino acids selected from 3 ,4-dihydroxyphenyl-L-alanine (DOPA) and a DOPA-derivative; or (ii) a plurality of peptides , each peptide comprising between 2 and 9 amino acids , at least one of which is an aromatic amino acid selected from 3 ,4-dihydroxyphenyl-L-alanine (DOPA) and a DOPA-derivative; or (iii) a combination of said amino acids and peptides; wherein said micro- or nano-structure has at least one property selected from bioadhesive , anti-oxidant , anti-fouling , anti-bacterial and any combination thereof.43. The micro- or nano-structure of claim 42 , which is selected from the group consisting of a fibrillar micro- or nano-structure claim 42 , a tubular micro- or nano-structure claim 42 , a spherical micro- or nano-structure and a ribbon-like micro- or nano-structure.44. The micro- or nano-structure of claim 43 , which is at least about 1 nm in diameter claim 43 , and which does not exceed about 500 nm in diameter.45. The micro- or nano-structure of claim 42 , wherein each peptide in said plurality of peptides comprises between 2 and 7 amino acids.46. The micro- or nano-structure of claim 42 , comprising a combination of said amino acids and said peptides.47. The micro- or nano-structure of claim 42 , wherein each peptide in said plurality of peptides comprises a plurality of aromatic amino ...

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Номер записи: 54
17-07-2014 дата публикации

INTRAESOPHAGEAL ADMINISTRATION OF TARGETED NITROXIDE AGENTS FOR PROTECTION AGAINST IONIZING IRRADIATION-INDUCED ESOPHAGITIS

Номер: US20140199368A1
Автор: Epperly Michael W., Gao Xiang, Greenberger Joel S., Li Song, Wipf Peter
Принадлежит: University of Pittsburg-Of the Commonwealth System of Higher Education-Office of Technolology Manage

Provided herein are compositions and related methods useful for prevention or mitigation of ionizing radiation-induced esophagitis. The compositions comprise compounds comprising a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent or mitigate esophageal damage caused by radiation. 12. The method of claim 11 , in which R is Ac claim 11 , Boc claim 11 , Cbz claim 11 , or —P(O)-Ph.13. The method of in which R1 claim 11 , R2 and R3 independently are methyl claim 11 , ethyl claim 11 , propyl claim 11 , 2-propyl claim 11 , butyl claim 11 , t-butyl claim 11 , pentyl claim 11 , hexyl claim 11 , benzyl claim 11 , hydroxybenzyl claim 11 , phenyl and hydroxyphenyl.14. The method of claim 11 , in which R4 is 2 claim 11 ,2 claim 11 ,6 claim 11 ,6-Tetramethyl-4-piperidine 1-oxyl claim 11 , 1-methylazaadamantane N-oxyl) claim 11 , or 1 claim 11 ,1 claim 11 ,3 claim 11 ,3-tetramethylisoindolin-2-yloxyl.1520-. (canceled)2426-. (canceled)27. The method of claim 1 , in which the compound is selected from the group consisting of: XJB-5-131 claim 1 , XJB-5-125 claim 1 , XJB-5-197 claim 1 , XJB-7-53 claim 1 , XJB-7-55 claim 1 , XJB-7-75 claim 1 , JP4-049 claim 1 , XJB-5-208 claim 1 , JED-E71-37 claim 1 , JED-E71-58.28. The method of claim 1 , in which the amount effective to prevent or mitigate ionizing irradiation-induced esophagitis in the subject ranges from 0.1 to 100 mg/kg in the subject.2931-. (canceled)32. The method of claim 1 , in which the compound is administered between 30 minutes and one hour after radiation exposure in the subject.33. The method of claim 1 , in which the compound is administered prior to radiation exposure in the subject.34. The method of in which the compound is formulated in an oral liquid dosage form.35. The method of claim 34 , in ...

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Номер записи: 55
25-08-2022 дата публикации

COMPOUNDS FOR PROTEASOME ENZYME INHIBITION

Номер: US20220267372A1
Автор: LAIDIG Guy J., SMYTH Mark S.
Принадлежит:

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Nn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. 149.-. (canceled)51. The method of claim 50 , wherein compound (B) is admixed as a salt.52. The method of claim 51 , wherein compound (B) is admixed as the trifluoroacetate salt.53. The method of claim 50 , wherein step (a) is performed in the presence of a peptide coupling agent.54. The method of claim 53 , wherein the peptide coupling agent comprises PyBOP.55. The method of claim 50 , wherein compound (E) is admixed as a trifluoroacetate salt.56. The method of claim 50 , wherein step (c) is performed in the presence of a peptide coupling agent.57. The method of claim 56 , wherein the peptide coupling agent comprises PyBOP claim 56 , HOBT claim 56 , or both.58. The method of claim 50 , further comprising (d) isolating compound 8 via filtration. This application claims the benefit of priority of U.S. Provisional Patent Application Ser. No. 60/599,401 filed on Aug. 6, 2004 and U.S. Provisional Patent Application Ser. No. 60/610,001 filed Sep. 14, 2004 and is a continuation-in-part of U.S. patent application Ser. No. 11/106,879 filed Apr. 14, 2005. The teachings of all of the referenced applications are incorporated by reference in their entirety.This invention relates to compounds and methods for enzyme inhibition. In particular, the invention relates to therapeutic methods based on enzyme inhibition.In ...

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Номер записи: 56
12-05-2016 дата публикации

INHIBITORS OF HEPATITIS C VIRUS

Номер: US20160130300A1
Автор: Bjornson Kyla, Canales Eda, Cottell Jeromy J., Karki Kapil K., Katana Ashley A., Kato Darryl, Kobayashi Tetsuya, Link John O., Martinez Ruben, Phillips Barton W., Pyun Hyung-jung, Sangi Michael, Schrier Adam J., Siegel Dustin, Taylor James G., Tran Chinh V., Trejo Martin Teresa A., Vivian Randall W., Yang Zheng-Yu, Zablocki Jeff, Zipfel Sheila
Принадлежит:

Compounds of Formula I are disclosed 2. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is C-Calkyl.3. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is methyl or ethyl.4. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Ccarbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons claim 1 , wherein said C-Ccarbocyclene is optionally substituted with C-Calkyl or C-Chaloalkyl.5. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Ccarbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons claim 1 , wherein the C-Ccarbocyclene is optionally substituted with methyl claim 1 , ethyl or trifluoromethyl.6. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is cyclopropylene.7. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Cbridged bicyclic carbocyclylene or C-Cfused bicyclic carbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons.8. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is ...

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Номер записи: 57
10-05-2018 дата публикации

MULTIFUNCTIONAL OPIOID RECEPTOR LIGANDS AND METHODS OF TREATING PAIN

Номер: US20180127465A1
Автор: Hruby Victor J., LEE Yeon Sun, PORRECA Frank
Принадлежит:

Opioid receptor ligands (ORLs) that are multifunctional having agonist activity at mu opioid receptor (MOR), agonist activity at delta opioid receptor (DOR), and antagonist (or partial agonist) activity at kappa opioid receptor (KOR). The ORLs comprise peptide portions that are analogs derived from enkephalins, EM-1, or DALDA, as well as tail portions that comprise a lipophilic molecule such as a 4-anilidopiperidine moiety. 1. A multifunctional opioid receptor ligand (ORL) according to Formula 1: Aaa-Bbb-Ccc-Ddd(X)-Eee , whereinAaa is selected from 2′-6′-dimethyltyrosine (Dmt), Tyrosine (Tyr), Tmt, Phe, Dmp, and Mdp;Bbb is selected from D-Alanine (D-Ala), Alanine (Ala), D-Norleucine (D-Nle), Norleucine (Nle), Proline (Pro), D-Proline (D-Pro), Arginine (Arg), D-Arginine (D-Arg), and tetrahydroisoquinoline-3-carboxylic acid (Tic), and D-Tic;Ccc is selected from Gly, Phenylalanine(X) (Phe(X)), Trp, and naphthylalanine (Nal) or is absent;Ddd(X) is Gly, Phe(X), Trp, Nal, or Lys; andEee comprises N-phenyl-N-piperidin-4-ylpropionamide-R (Ppp(R)) wherein X and R both comprise a halogen, X is selected from H, F, Cl, and Br, R is selected from F, Cl, and Br;wherein the multifunctional ORL has agonist activity at mu opioid receptor (MOR), agonist activity at delta opioid receptor (DOR), and antagonist activity at kappa opioid receptor (KOR).2. The ORL of claim 1 , wherein R is selected from 3-Cl claim 1 , 4-Cl claim 1 , 3-F claim 1 , 4-F claim 1 , and 2 claim 1 ,4-diCl.3. A multifunctional opioid receptor ligand (ORL) according to Formula 4: Aaa-Bbb-Ccc-Ddd(X)-Yyy(n)-Eee claim 1 , whereinAaa is selected from 2′-6′-dimethyltyrosine (Dmt), Tyrosine (Tyr), Tmt, Phe, Dmp, and Mdp;Bbb is selected from D-Alanine (D-Ala), D-Norleucine (D-Nle), Proline (Pro), and D-Arginine (D-Arg), tetrahydroisoquinoline-3-carboxylic acid (Tic), D-Tic;Ccc is selected from Gly, Phenylalanine(X) (Phe(X)), Trp, and naphthylalanine (Nal) or is absent, wherein X is a halogen;Ddd(X) is Gly, Phe(X), Trp, ...

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Номер записи: 58
01-09-2022 дата публикации

PEPTIDOMIMETICS FOR THE TREATMENT OF CORONAVIRUS AND PICORNAVIRUS INFECTIONS

Номер: US20220273753A1
Автор: Amblard Franck, SCHINAZI RAYMOND F., Zandi Keivan
Принадлежит:

Compounds, compositions and methods for preventing, treating or curing a coronavirus, picornavirus, and/or hepeviridae virus infection in human subjects or other animal hosts. Specific viruses that can be treated include enteroviruses. In one embodiment, the compounds can be used to treat an infection with a severe acute respiratory syndrome virus, such as human coronavirus 229E, SARS, MERS, SARS-CoV-1 (OC43), and SARS-CoV-2. In another embodiment, the methods are used to treat a patient co-infected with two or more of these viruses, or a combination of one or more of these viruses and norovirus. 130-. (anceled)32. The method of claim 31 , wherein Ris C(O)H.33. The method of claim 31 , wherein Ris alkylaryl or alkylheteroaryl.35. The method of claim 31 , wherein Ris thiophene.36. The method of claim 31 , wherein X is O claim 31 , Rand R′ are H claim 31 , and Ris an optionally substituted phenyl.37. The method of claim 31 , wherein X=a covalent bond claim 31 , p=0 claim 31 , and Ris an optionally substituted aryl or heteroaryl.3824. The method of claim claim 31 , wherein the heteroaryl ring is a pyrazine claim 31 , thiophene claim 31 , isoxazole claim 31 , or oxazole ring.39. The method of claim 31 , wherein Ris phenyl claim 31 , halo-substituted phenyl claim 31 , or naphthyl.40. The method of claim 31 , wherein the Hepeviridae virus is the hepatitis E virus.41. The method of claim 31 , wherein the picornavirus is an enterovirus.42. The method of claim 31 , wherein the virus is a causative agent for multiple sclerosis claim 31 , SARS claim 31 , MERS claim 31 , or COVID-19.43. The method of claim 31 , wherein the virus is a causative agent for a respiratory infection.44. The method of claim 31 , wherein the method further comprising administering another anti-coronavirus or picornavirus virus agent in combination or alternation with the compound of any of Formulas I-VI.45. The method of claim 31 , wherein the patient is co-infected with norovirus claim 31 , and the ...

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Номер записи: 59
11-05-2017 дата публикации

Process for Preparing D-Arginyl-2,6-Dimethyl-L-Tyrosyl-L-Lysyl-L-Phenylalaninamide

Номер: US20170129920A1
Автор: Cornille Fabrice, Gao Hanrong, Yu Xiaozhong, Zhao Xinjun, Zheng Minyu
Принадлежит:

The invention relates to a process for solution-phase synthesis of D-Arginyl-2,6-dimethyl-L-tyrosyl-L-lysyl-L-phenylalaninamide, an active ingredient used for both common and rare diseases including a mitochondrial targeted therapy for ischemia reperfusion injury. 2. A process according to wherein the coupling between (II) and (III) and/or the coupling between (VI) and (VII) and/or the coupling between (IX) and (X) is performed in the presence of N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate.3. A process according to wherein the coupling between (II) and (III) and/or the coupling between (VI) and (VII) and/or the coupling between (IX) and (X) is performed in the presence of a tertiary amine claim 2 , preferably selected from N-methyl morpholine claim 2 , triethylamine or diisopropylethylamine.4. A process according to wherein the coupling between (II) and (III) and/or the coupling between (VI) and (VII) and/or the coupling between (IX) and (X) is performed in organic polar solvents.5. A process according to wherein the coupling between (II) and (III) is performed in a temperature range between 0° C. and 60° C.6. A process according to wherein the formation of methanesulfonic salt (VI) is obtained in methylene chloride as solvent and crystallized from the same solvent.7. A process according to wherein the coupling between (VI) and (VII) is performed in a temperature range between 0° C. and 60° C.8. A process according to wherein the coupling between (IX) and (X) is performed in a temperature range between 0° C. and 60° C.9. A process according to wherein the step of deprotecting compound (XI) is performed by hydrogenation.14. A compound according to in form of the mesylate salt.16. A process according to claim 4 , wherein said organic polar solvents is selected from dimethylformamide claim 4 , acetonitrile claim 4 , tetrahydrofuran claim 4 , 2-methyl tetrahydrofuran claim 4 , or a mixture thereof. The invention ...

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Номер записи: 60
11-05-2017 дата публикации

DISCOVERY OF THE FIRST SELECTIVE C5A2 RECEPTOR (C5L2/C5AR2) LIGANDS

Номер: US20170129921A1
Автор: Cooper Matthew A., Croker Daniel E., Floudas Christodoulos A., Monk Peter N., Morikis Dimitrios, Woodruff Trent M.
Принадлежит:

A method of selectively modulating the activity of C5a receptor 2 (C5aR2). The method includes exposing the receptor to a compound that selectively modulates C5aR2 compared to C5a receptor 1 (C5aR1). In some cases, the compound is peptide P32 or P59. Methods of recruiting β-arrestin 2 in a cell, modulating C5a-induced ERK1/2 activation in a macrophage, selectively inhibiting the release of IL-6 from a macrophage, are also provided. 1. A method of selectively modulating the activity of C5a receptor 2 (C5aR2) , comprising exposing the receptor to a C5aR2 ligand that selectively modulates C5aR2 compared to C5a receptor 1 (C5aR1).2. The method of claim 1 , wherein the C5aR2 is on the surface of or inside a cell.3. The method of claim 2 , wherein the cell is in a subject or in culture.4. The method of claim 1 , wherein the ligand acts as a C5aR2 agonist or antagonist.5. The method of claim 1 , wherein the ligand is a polypeptide or peptide comprising SEQ ID NO:1 or SEQ ID NO:2.6. The method of claim 1 , wherein the ligand is a peptide comprising SEQ ID NO:1 or SEQ ID NO:2 claim 1 , or an analog claim 1 , sequence variant claim 1 , peptide surrogate claim 1 , or peptidomimetic of the peptide.7. A method of recruiting β-arrestin 2 in a cell claim 1 , modulating C5a-induced ERK1/2 activation in a macrophage claim 1 , selectively inhibiting release of IL-6 from a macrophage claim 1 , or any combination thereof claim 1 , comprising exposing the cell or macrophage to a C5aR2 ligand that selectively modulates C5aR2 compared to C5aR1.8. The method of claim 7 , wherein the cell or macrophage is in culture or in a subject.9. The method of claim 7 , wherein the ligand is a polypeptide or peptide comprising SEQ ID NO:1 or SEQ ID NO:2.10. The method of claim 7 , wherein the ligand is a peptide comprising SEQ ID NO:1 or SEQ ID NO:2 claim 7 , or an analog claim 7 , sequence variant claim 7 , peptide surrogate claim 7 , or peptidomimetic of the peptide.11. A method of treating a disease ...

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Номер записи: 61
19-05-2016 дата публикации

NOVEL COMPOUNDS

Номер: US20160136230A1
Автор: CAMPOS Sebastien Andre, Harling John David
Принадлежит:

A compound of formula (I): 2. A compound or a pharmaceutically acceptable salt thereof according to wherein Ris 4-methylthiazol-5-yl claim 1 , oxazol-5-yl.3. A compound or a pharmaceutically acceptable salt thereof according to wherein Ris 4-methylthiazol-5-yl.6. A compound or a pharmaceutically acceptable salt thereof according to wherein at least one Ris N(CH).7. A compound or a pharmaceutically acceptable salt thereof according to wherein the linker is OCHCHN(CH)CHCHOCHCHOCHCHOCH.9. (canceled)10. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof according to and one or more of pharmaceutically acceptable carriers claim 1 , diluents and excipients.11. A method of treating diseases and conditions mediated by the estrogen receptor in a subject comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof according to .12. (canceled)13. A combination comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof according to and at least one further therapeutic agent.1415-. (canceled)16. A method of treating diseases and conditions mediated by the estrogen receptor comprising administering to a human in need thereof a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. according to .17. (canceled)18. A combination comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof according to and at least one anti-neoplastic agent.1921-. (canceled)22. A method of treating diseases and conditions mediated by the estrogen receptor claim 1 , comprising administering to a human in need thereof a therapeutically effective amount of a combination comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof according to and at least one anti-neoplastic agent.23. A pharmaceutical composition comprising a combination comprising a ...

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Номер записи: 62
19-05-2016 дата публикации

ALPHA-OXOACYL AMINO-CAPROLACTAM DERIVATIVE

Номер: US20160137691A1
Автор: Ishikawa Mizuho, KOBAYASHI Nobuo, Koji Tsuneo, Kunii Hisatomo, MORITA Daisuke
Принадлежит:

The purpose of the present invention is to provide a pharmaceutical composition that is useful for the treatment of diseases that are caused by an increase in bone resorption and that does not cause serious side effects even when used in combination with another drug. The present invention relates to: an α-oxoacyl aminocaprolactam derivative that is represented by formula (I) 2. The α-oxoacylaminocaprolactam derivative according to claim 1 , wherein in formula (I) claim 1 , X is —O—.3. The α-oxoacylaminocaprolactam derivative according to claim 1 , wherein in formula (I) claim 1 , X is —N(R)— claim 1 , wherein Ris a (C1 to C10 alkoxy)carbonyl group.4. The α-oxoacylaminocaprolactam derivative according to claim 3 , wherein Ris a methoxycarbonyl group.5. A pharmaceutical composition comprising the α-oxoacylaminocaprolactam derivative according to and a pharmaceutically acceptable carrier.6. The pharmaceutical composition according to claim 5 , which is a medicament for treating or preventing a disease caused by accelerated bone resorption.7. The pharmaceutical composition according to claim 6 , wherein the disease caused by accelerated bone resorption is osteoporosis claim 6 , hypercalcemia claim 6 , Paget's disease claim 6 , bone resorption disease claim 6 , osteogenesis imperfecta claim 6 , osteoarthritis claim 6 , rheumatoid arthritis claim 6 , arthritis claim 6 , Klinefelter syndrome claim 6 , hereditary hyperphosphatasia claim 6 , Charcot neuroarthropathy claim 6 , mastocytosis claim 6 , Gaucher disease claim 6 , cancer metastasis claim 6 , or multiple myeloma. The present invention relates to a novel α-oxoacylaminocaprolactam derivative. Specifically, the present invention relates to an α-oxoacylaminocaprolactam derivative having the effect of selectively inhibiting cathepsin K, which is the principal cysteine protease particularly involved in bone resorption.In recent years, as the aging society rapidly develops, the number of patients with senile diseases, ...

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Номер записи: 63
03-06-2021 дата публикации

BIOLOGICALLY ACTIVE C-TERMINAL ARGININE-CONTAINING PEPTIDES

Номер: US20210163880A1
Автор: Breece Tim, Shiratori Masaru Ken, Wilkins James
Принадлежит:

The present invention concerns the separation, identification and characterization of active peptide fragments from peptones. 1. A method for the promotion of cell growth in a recombinant host cell culture comprising a recombinant host cell , the method comprising culturing said host cell with a culture medium that comprises a mixture of one or more tri-peptides selected from the group consisting of EVR , DPR , TVR , EIR , ELR , INR , LNR , OVR , AVR , GIR , GLR , IVR , LVR , ITR , LTR , DTR , ESR , GGR , DVR , ILR , LLR , AIR , ALR , ADR , EGR , AGR , DOR , ENR , DMR , EMR , GTR , FPR , LMR , IPR , and LPR; and one or more di-peptides selected from the group consisting of PR , DR , VR , ER , NR , OR , and GR;wherein said mixture of peptides is in the absence of any peptide having a molecular mass of 500 Da or more;wherein said culture medium is a defined culture medium; andwherein said host cell is a mammalian host cell.2. The method of claim 1 , wherein said mixture is obtained by fractionation of a peptone or is chemically synthesized.3. The method of claim 2 , wherein said peptone is a component-3 of protease peptidone (PP3).47-. (canceled)8. The method of claim 1 , wherein said mammalian host cell is a Chinese Hamster Ovary (CHO) cell.9. The method of claim 1 , wherein said recombinant host cell produces a heterologous protein.10. The method of claim 9 , wherein said heterologous protein is an antibody or antibody fragment.11. The method of claim 1 , wherein said mixture of peptides is part of a combinatorial peptide library. This is a divisional application of application Ser. No. 12/932,207, filed Feb. 18, 2011, which is a divisional application of application Ser. No. 12/231,917, filed Sep. 5, 2008 under 37 CFR 1.53(b)(1), claiming priority under 35 USC 119(e) to provisional application No. 60/967,644 filed Sep. 5, 2007, the contents of which are incorporated herein by reference.The present invention concerns the separation, identification and ...

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Номер записи: 64
17-05-2018 дата публикации

NOVEL INHIBITORS OF MAMMALIAN TIGHT JUNCTION OPENING

Номер: US20180133281A1
Автор: Tamiz Amir
Принадлежит:

The present invention provides novel peptides that inhibit and/or reduce the opening of mammalian tight junctions, i.e. peptide tight junction antagonists. The present invention also provides methods for the treatment of excessive or undesirable permeability of a tissue by administering to a subject suffering from such a condition a composition comprising a peptide tight junction antagonist of the invention. 1. A peptide tight junction antagonist , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-69.2. The peptide tight junction antagonist of claim 1 , wherein the peptide is eight to ten amino acids in length.3. The peptide tight junction antagonist of claim 1 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11 claim 1 , 13 claim 1 , 17 claim 1 , 18 claim 1 , 20-32 claim 1 , 34 claim 1 , 35 claim 1 , 54 claim 1 , 57 claim 1 , and 67-69.4. The peptide tight junction antagonist of claim 1 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-69.5. The peptide tight junction antagonist of claim 1 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11 claim 1 , 13 claim 1 , 17 claim 1 , 18 claim 1 , 20-32 claim 1 , 34 claim 1 , 35 claim 1 , 54 claim 1 , 57 claim 1 , and 67-69.6. The peptide tight junction antagonist of claim 1 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-69.7. The peptide tight junction antagonist of claim 1 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11 claim 1 , 13 claim 1 , 17 claim 1 , 18 claim 1 , 20-32 claim 1 , 34 claim 1 , 35 claim 1 , 54 claim 1 , 57 claim 1 , and 67-69.8. A method of treating an excessive or undesirable permeability of a tissue containing tight junctions ...

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Номер записи: 65
31-05-2018 дата публикации

PROCESS FOR PREPARATION OF NITROGEN MUSTARD DERIVATIVES

Номер: US20180148473A1
Автор: Wahlström Niklas Håkan, Wennerberg Johan Anders
Принадлежит: ONCOPEPTIDES AB

The present invention provides a process for the production of compound (III) or a deprotected product thereof: comprising reacting compound (II) with chloroacetic acid, in the presence of a reducing agent; wherein PG is a protecting group and R is OH in a suitably protected form or (A). The invention further provides intermediate compounds formed in the process of the invention, and processes for the production of intermediate compounds. 2. A process as claimed in claim 1 , which is performed in the presence of a reducing agent selected from the group consisting of borane claim 1 , a borane-Lewis base complex claim 1 , a borohydride claim 1 , a metal hydride claim 1 , and Hin the presence of a metal catalyst.3. A process as claimed in claim 2 , wherein the reducing agent is BHor borane dimethylsulfide.4. A process as claimed in any one of to claim 2 , wherein PG is selected from the group consisting of methyl oxycarbonyl claim 2 , ethyl oxycarbonyl claim 2 , 9-fluorenylmethyl oxycarbonyl claim 2 , t-butyl oxycarbonyl claim 2 , benzyl oxycarbonyl claim 2 , p-methoxybenzyl oxycarbonyl claim 2 , 1-adamantyl oxycarbonyl claim 2 , p-bromobenzyl oxycarbonyl claim 2 , trifluoroacetyl claim 2 , chloroacetyl claim 2 , phenylacetyl claim 2 , benzacetyl claim 2 , p-toluenesulfonyl claim 2 , 2-nitrobenzenesulfonyl claim 2 , t-butylsulfonyl claim 2 , 2- or 4-nitrobenzenesulfonyl claim 2 , 2 claim 2 ,4-dinitronenzesulfonyl claim 2 , and 2-naphthalenesulfonyl.5. A process as claimed in 4 claim 2 , where PG is t-butyl oxycarbonyl.6. A process as claimed in any one of to claim 2 , which is performed at a temperature in the range of from 3 to 50° C. claim 2 , for example 4 to 45° C.7. A process as claimed in any one of to claim 2 , which is performed at a temperature in the range of from 5 to 40° C.8. A process as claimed in any one of to claim 2 , which is performed in the presence of a buffering agent.9. The process as claimed claims 8 , wherein the buffering agent is a ...

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Номер записи: 66
17-06-2021 дата публикации

COMPOUNDS FOR PROTEASOME ENZYME INHIBITION

Номер: US20210179663A1
Автор: LAIDIG Guy J., SMYTH Mark S.
Принадлежит:

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. 2. A compound of claim 1 , wherein X is O.3. A compound of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , and Rare independently selected from Calkyl claim 2 , Chydroxyalkyl claim 2 , and Caralkyl; and Ris hydrogen.4. A compound of claim 3 , wherein Rand Rare independently Caralkyl and Rand Rare independently Calkyl.5. A compound of claim 4 , wherein R claim 4 , R claim 4 , R claim 4 , and Rare all hydrogen.6. A compound of claim 5 , wherein Y is selected from N-alkyl claim 5 , O claim 5 , and CH.7. A compound of claim 6 , wherein Z is CH claim 6 , and m and n are both 0.8. A compound of claim 6 , wherein Z is CH claim 6 , m is 0 claim 6 , and n is 2 or 3.9. A compound of claim 6 , wherein Z is O claim 6 ,m is 1 claim 6 , and n is 2.17. A compound of claim 16 , wherein Xis O.18. A compound of claim 17 , wherein R claim 17 , R claim 17 , R claim 17 , and Rare independently selected from Calkyl claim 17 , Chydroxyalkyl claim 17 , and Caralkyl.19. A compound of claim 18 , wherein Rand Rare independently Caralkyl and Rand Rare independently Calkyl.21. A compound of claim 20 , wherein X is O.22. A compound of claim 21 , wherein Rand Rare independently selected from Callyl claim 21 , Chydroxyalkyl claim 21 , and Caralkyl.23. A compound of claim 22 , wherein Rand Rare independently Calkyl.24. A compound ...

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Номер записи: 67
01-06-2017 дата публикации

PROCESS FOR THE PRODUCTION OF D-ARGINYL-2,6-DIMETHYL-L-TYROSYL-L-LYSYL-L-PHENYLALANINAMIDE

Номер: US20170152289A1
Автор: Cornille Fabrice, Gao Hanrong, Yu Xiaozhong, Zhao Xinjun, Zheng Minyu
Принадлежит:

The invention relates to a process for solution-phase synthesis of D-Arginyl-2,6-dimethyl-L-tyrosyl-L-lysyl-L-phenylalaninamide, an active ingredient used for both common and rare diseases including a mitochondrial targeted therapy for ischemia reperfusion injury. 2. A process according to wherein the deprotection is performed by simultaneous acidolysis of the three Boc groups with organic acids.3. A process according to wherein the deprotection is performed by simultaneously acidolysis of the three Boc group with trifluoroacetic acid claim 1 , without use of Pd catalysts.4. A process according to the wherein the acidolysis can be performed with other acids such as HCI or HBr claim 1 , leading to the corresponding salts.5. A process according to wherein the final product (I) is obtained in solid crystalline form of the trifluoroacetate salt after simple crystallization without any need of HPLC purification or any freeze-drying.6. A process according the wherein the coupling between (II) and (III) is performed in the presence of N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetramethyl-O-(benzotriazol-1-yl)uranium tetrafluoroborate (known as TBTU) and polar solvents such as NMP claim 1 , DMF claim 1 , acetonitrile claim 1 , DMSO and THF.7. A process according the wherein coupling between (II) and (III) is performed in a temperature range between −10° C._and 50° C.8. A process according the wherein formation of methanesulfonic salt (VI) is obtained in methanol claim 1 , NMP claim 1 , acetonitrile or THF as solvent and crystallized from the same solvent.9. A process according the wherein the coupling reaction between compound (IX) and compound (X) is performed in the presence of N claim 1 ,N claim 1 ,N′ claim 1 ,N′-tetramethyl-O-(benzotriazol-1-yl)uranium tetrafluoroborate (TBTU) and polar solvents selected from NMP claim 1 , DMF claim 1 , acetonitrile claim 1 , DMSO and THF. The invention relates to a process for solution-phase synthesis of D-Arginyl-2,6-dimethyl-L-tyrosyl-L- ...

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Номер записи: 68
09-06-2016 дата публикации

URIC ACID-LOWERING AGENT

Номер: US20160159858A1
Автор: BEPPU Yoshinori, Fukizawa Shinya, SUZUKI Toshihide, Watanabe Hiroshi
Принадлежит: SUNTORY HOLDINGS LIMITED

A uric acid-lowering agent containing, as an active ingredient, a tyrosine-containing cyclic dipeptide selected from the group consisting of cyclotryptophanyltyrosine, cycloseryltyrosine, cycloprolyltyrosine, cyclotyrosylglycine, cyclotyrosyltyrosine, cyclophenylalanyltyrosine, cycloleucyltyrosine, cyclolysyltyrosine, cyclohistidyltyrosine, cycloalanyltyrosine, cycloglutamyltyrosine, cyclovalyltyrosine, cycloisoleucyltyrosine, cyclothreonyltyrosine, cycloaspartyltyrosine, cycloasparaginyltyrosine, cycloglutaminyltyrosine, cycloarginyltyrosine, cyclomethionyltyrosine, and cyclotyrosylcysteine, or a salt thereof. The uric acid-lowering agent of the present invention has an excellent action of lowering a uric acid level, and the uric acid-lowering agent is useful in, for example, prevention or treatment of hyperuricemia, gout or the like. 13-. (canceled)4. A composition for lowering a uric acid level , comprising one or more tyrosine-comprising cyclic dipeptides selected from the group consisting of cyclotryptophanyltyrosine , cycloseryltyrosine , cycloprolyltyrosine , cyclotyrosylglycine , cyclotyrosyltyrosine , cyclophenylalanyltyrosine , cycloleucyltyrosine , cyclolysyltyrosine , cyclohistidyltyrosine , cycloalanyltyrosine , cycloglutamyltyrosine , cyclovalyltyrosine , cycloisoleucyltyrosine , cyclothreonyltyrosine , cycloaspartyltyrosine , cycloasparaginyltyrosine , cycloglutaminyltyrosine , cycloarginyltyrosine , cyclomethionyltyrosine , and cyclotyrosylcysteine , or salts thereof.5. The composition for lowering a uric acid level according to claim 4 , wherein the composition is a treated product obtained by heat-treating a solution comprising a soybean peptide.68-. (canceled)9. A composition for inhibiting a xanthine oxidase comprising one or more tyrosine-comprising cyclic dipeptides selected from the group consisting of cyclotryptophanyltyrosine claim 4 , cycloseryltyrosine claim 4 , cycloprolyltyrosine claim 4 , cyclotyrosylglycine claim 4 , ...

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Номер записи: 69
23-05-2019 дата публикации

Psma-targeted nir dyes and their uses

Номер: US20190151480A1
Автор: Mini Thomas, Sumith A Kularatne
Принадлежит: On Target Laboratories, LLC

The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing prostate specific membrane antigen (PSMA), such as prostate cancer and related diseases. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.

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Номер записи: 70
23-05-2019 дата публикации

ANTI-INFLAMMATORY TRIPEPTIDES

Номер: US20190153029A1
Автор: Abels Christoph, Knie Ulrich, Soeberdt Michael
Принадлежит:

The present invention relates to tripeptide compounds according to the general formula (1) and their use as a medicament, in particular as anti-inflammatory agents. 2. The tripeptide compound according to claim 1 , selected from the group consisting of H-(L)-Lys-(D)-Pro-N-methyl-(L)-Thr-OH claim 1 , N claim 1 ,N-dimethyl-(L)-Lys-(D)-Pro-N-methyl-(L)-Thr-OH claim 1 , N claim 1 ,N-dimethyl-(L)-Lys-(p)-Pro-N-methyl-(L)-Thr-NH claim 1 , and N claim 1 ,N-dimethyl-(L)-Lys-(D)-Pro-N-methyl-(L)-Val-OH claim 1 , or a solvate or hydrate thereof or a pharmaceutically acceptable salt thereof.3. The tripeptide compound according to claim 1 , wherein the tripeptide compound is N claim 1 ,N-dimethyl-(L)-Lys-(D)-Pro-N-methyl-(L)-Thr-OH claim 1 , or a solvate or hydrate thereof or a pharmaceutically acceptable salt thereof.4. The tripeptide compound according to claim 1 , wherein the tripeptide compound is N claim 1 ,N-dimethyl-(L)-Lys-(D)-Pro-N-methyl-(L)-Thr-NH claim 1 , or a solvate or hydrate thereof or a pharmaceutically acceptable salt thereof.5. The tripeptide compound according to claim 1 , wherein the tripeptide compound is N claim 1 ,N-dimethyl-(L)-Lys-(D)-Pro-N-methyl-(L)-Val-OH claim 1 , or a solvate or hydrate thereof or a pharmaceutically acceptable salt thereof.6. A method of therapeutic and/or prophylactic treatment of disease claim 1 , comprising: administering the tripeptide compound according to .7. The method of claim 6 , wherein the disease is selected from the group consisting of: an acute inflammatory disease claim 6 , a chronic inflammatory disease claim 6 , acute pain claim 6 , chronic pain claim 6 , pruritus claim 6 , hyponatremia claim 6 , edema claim 6 , ileus claim 6 , tussis claim 6 , and glaucoma.8. The method of claim 7 , wherein the inflammatory disease is selected from the group consisting of: cardiovascular inflammation claim 7 , neurological inflammation claim 7 , skeletal inflammation claim 7 , skin inflammation claim 7 , muscular inflammation ...

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Номер записи: 71
08-06-2017 дата публикации

EPOXYKETONE COMPOUNDS FOR ENZYME INHIBITION

Номер: US20170158734A1
Автор: CEN Jian James, FAN Xiaoqing Michelle, YANG Jinfu
Принадлежит: Centrax International, Inc.

The present disclosure relates to novel compounds and pharmaceutical compositions thereof which are useful as inhibitors of proteasomes. The compounds provided herein have improved proteasome potency and selectivity, and increased aqueous solubility, and are useful in treating various conditions or diseases associated with proteasomes. 4. The compound of claim 1 , wherein Ris Calkyl claim 1 , Calkoxyalkyl claim 1 , aryl claim 1 , heteroaryl claim 1 , Caralkyl or Cheteroaralkyl.5. The compound of claim 4 , wherein Ris methyl-oxy-methyl claim 4 , 4-pyridylmethyl claim 4 , isobutyl claim 4 , benzyl or 4-thiazolyl-methyl.6. The compound of claim 1 , wherein Ris Calkyl claim 1 , aryl claim 1 , heteroaryl claim 1 , Caralkyl or Cheteroaralkyl.7. The compound of claim 6 , wherein Ris isobutyl claim 6 , 4-pyridylmethyl or benzyl.9. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.10. A method of specifically inhibiting catalytic activity of 20S proteasome claim 1 , comprising administering a therapeutically effective amount of a compound of .11. The method of claim 10 , wherein the CT-L activity and T-L activity of the 20S proteasome are simultaneously inhibited.12. A method of treating a proteasome-related disease or condition claim 1 , comprising administering a therapeutically effective amount of a compound of .13. The method of claim 12 , wherein the compound is administered through a parenteral route.14. The method of claim 13 , wherein the compound is administered subcutaneously claim 13 , intravenously claim 13 , intramuscularly claim 13 , intraarterially claim 13 , intrathecally claim 13 , intracapsularly claim 13 , intraorbitally claim 13 , intra cardiacally claim 13 , intradermally claim 13 , intraperitoneally claim 13 , transtracheally claim 13 , subcuticularly claim 13 , intraarticularly claim 13 , subcapsularly claim 13 , subarachnoidly claim 13 , intraspinally claim 13 , intrasternally claim 13 , or ...

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Номер записи: 72
25-06-2015 дата публикации

HCV PROTEASE INHIBITORS AND USES THEREOF

Номер: US20150175657A1
Автор: Niu Deqiang, Petter Russell C., Qiao Lixin, Signh Juswinder
Принадлежит:

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same. 14. The compound of any one of , , , , , or , wherein Ris n-propyl.16. The compound of any one of , , , , , or , wherein Ris cyclopropyl.17. The compound of claim 1 , wherein Ris —NHC(O)OR.18. The compound of any one of claim 1 , claim 1 , claim 1 , claim 1 , claim 1 , or claim 1 , wherein Ris an optionally substituted 5-10 membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.2013. The compound of any one of claim 1 , claim 1 , claim 1 , claim 1 , claim 1 , claim 1 , or claim 1 , wherein Ris an optionally substituted Caliphatic group.21. The compound of claim 20 , wherein Ris t-butyl.22. The compound of any one of claim 20 , claim 20 , claim 20 , claim 20 , claim 20 , or claim 20 , wherein Ris an optionally substituted Ccycloalkyl group.23. The compound of claim 22 , wherein Ris cyclohexyl.24. The compound according to claim 1 , wherein Ris —(CH)-L-Y claim 1 , wherein:n is an integer from 0 to 5, inclusive;{'sub': 2-8', '2', '2', '2, 'L is a bivalent Cstraight or branched, hydrocarbon chain wherein L has at least one double bond and one or two additional methylene units of L are optionally and independently replaced by —NRC(O)—, —C(O)NR—, —N(R)SO—, —SON(R)—, —S—, —S(O)—, —SO—, —OC(O)—, —C(O)O—, cyclopropylene, —O—, —N(R)—, or —C(O)—;'}{'sub': 1-6', '2, 'sup': 'e', 'Y is hydrogen, Caliphatic optionally substituted with oxo, halogen, NO, or CN, or a 3-10 membered monocyclic or bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein said ring is substituted with 1-4 Rgroups; and'}{'sup': 'e', 'sub': 2', '1-6', '2, 'claim-text': [{'sub': 1-6', '2', '2', '2, 'Q is a covalent bond or a bivalent Csaturated or unsaturated, straight or branched, hydrocarbon chain, wherein one or two methylene ...

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Номер записи: 73
11-09-2014 дата публикации

BIFUNCTIONAL COMPOUNDS

Номер: US20140256654A1
Автор: Epperly Michael W., Goff Julie Pamela, Greenberger Joel S., Sprachman Melissa M., Wipf Peter
Принадлежит: University of Pittsburgh - of the Commonwealth System of Higher Education

A compound having the formula:

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Номер записи: 74
23-06-2016 дата публикации

INHIBITORS OF PROTEIN TYROSINE PHOSPHATASES

Номер: US20160176922A1
Автор: Zhang Sheng, ZHANG Zhong-Yin
Принадлежит: Indiana University Research and Technology Corpora tion

Disclosed herein are compounds that selectively inhibit members of the PTP family of enzymes. Synthesized compounds demonstrated selective inhibition of TC-PTP. Also provided are methods of using the compounds and formulations containing the compounds. Also described is a fluorescence-tagged combinatorial library synthesis and screening method. And methods of using these compounds to effect enzyme activity both in cells and in vitro as well as method of using these compounds to treat diseases in human and animals. 25-. (canceled)6. A method of treating an individual with a physiological disease claim 1 , disorder claim 1 , or condition associated with inappropriate activity of a protein tyrosine phosphatase comprising the step of administering to the individual a compound of in a therapeutically effective amount.7. The method of claim 6 , wherein the disease claim 6 , disorder claim 6 , or condition is selected from the group consisting: of type 1 diabetes claim 6 , type 2 diabetes claim 6 , obesity claim 6 , metabolic syndrome claim 6 , Crohn's disease claim 6 , rheumatoid arthritis claim 6 , Graves' disease claim 6 , systemic lupus erythematosus claim 6 , leukemia claim 6 , and tuberculosis.8. The method of claim 6 , wherein the PTP inhibitor is a selective TC-PTP inhibitor.920-. (canceled) This application is a Divisional application of U.S. patent application Ser. No. 13/260,623 filed Dec. 13, 2011, which claims the benefit of PCT Application No. PCT/US10/30409 filed Apr. 8, 2010, which claims the benefit of U.S. Provisional Application No. 61/167,627 filed Apr. 8, 2009, the complete disclosures of all of which are hereby expressly incorporated by reference.This invention was made with government support under CA126937 awarded by the National Institutes of Health. The United States Government has certain rights in the invention.Protein tyrosine phosphatases (PTPs) are an enzyme family comprising multiple enzyme subtypes, or isozymes, with differential activity ...

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Номер записи: 75
21-06-2018 дата публикации

PHARMACEUTICAL COMPOSITION FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASE COMPRISING THE PEPTIDE HAVING THE ABILITY TO INHIBIT ANGIOTENSIN-1 CONVERTING ENZYME AS AN ACTIVE INGREDIENT

Номер: US20180170961A1
Автор: Choi Yeung Joon, CHOUNG Se-Young
Принадлежит:

The present invention relates to a peptide separated from the fraction of oyster enzyme hydrate displaying the ability of suppressing angiotensin converting enzyme (ACE) and a pharmaceutical composition for the prevention and treatment of cardiovascular disease comprising the said peptide as an active ingredient. Particularly, the peptide separated from the fraction of the oyster enzyme hydrate of the present invention significantly inhibits ACE activity, and thus brings blood pressure regulating effect and antihypertensive effect. Therefore, the fraction of the oyster enzyme hydrate of the invention or the peptide separated from the same can be effectively used as an active ingredient of a pharmaceutical composition for the prevention or treatment of cardiovascular disease. 1. A method for treating cardiovascular disease comprising the step of administering a fraction of an oyster enzyme hydrate containing at least one peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1˜2 and SEQ ID NOs. 5˜11 to a subject having cardiovascular disease.2. The method according to claim 1 , wherein the fraction of the oyster enzyme hydrate has a molecular weight up to 10 kD.3. The method according to claim 1 , wherein the cardiovascular disease is one or more diseases selected from the group consisting of hypertension claim 1 , heart disease claim 1 , stroke claim 1 , thrombosis claim 1 , angina pectoris claim 1 , heart failure claim 1 , myocardial infarction claim 1 , atherosclerosis claim 1 , and arteriosclerosis. This application is a divisional of U.S. patent application Ser. No. 14/627,642 filed Feb. 20, 2015, which is a continuation-in-part of PCT/KR2013/007598 filed Aug. 23, 2013 which claims the benefit of Korean patent applications KR-10-2012-0092738 filed Aug. 24, 2012 and KR-10-2013-0100232 filed Aug. 23, 2013, the contents of each of which are incorporated herein by reference in their entirety.The present invention relates to a ...

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Номер записи: 76
28-05-2020 дата публикации

Self-assembled hybrid hydrogels formed of a short aromatic peptide and an aromatic amino acid

Номер: US20200165565A1
Автор: Ehud Gazit, Irena GRIGORIANTS, Lihi Adler-Abramovich, Rina SEVOSTIANOV
Принадлежит: Ramot at Tel Aviv University Ltd

Hybrid hydrogels, made of a three-dimensional network of fibrillar nanostructures, at least a portion of the fibrillar nanostructures being formed of at least two different types of aromatic moieties, at least one type of the aromatic moieties being an end-capping modified aromatic dipeptide and at least another type of the aromatic moieties being an amine-modified halogenated aromatic amino acid, are provided. Also provided are processes of preparing the hybrid hydrogels and uses thereof.

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Номер записи: 77
07-07-2016 дата публикации

IBAT INHIBITORS FOR THE TREATMENT OF LIVER DISEASES

Номер: US20160194353A1
Автор: Gillberg Per-Göran, Graffner Hans, Starke Ingemar
Принадлежит:

The present invention regards specific IBAT inhibitors useful in the prophylaxis and/or treatment of a liver disease. It also relates to compositions comprising these IBAT inhibitors, a method for treatment of the disorders and a kit comprising the substances or the compositions. 1. (canceled)3. The method according to claim 2 , wherein the compound of formula II is selected from the group consisting of:1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N-(carboxymethyl) carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N′—((S)-1-carboxyethyl) carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N—((S)-1-carboxypropyl) carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N—((R)-1-carboxy-2-methylthioethyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N—((S)-1-carboxypropyl) carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N—((R)-1-carboxy-2-methylthio-ethyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N—((S)-1-carboxy-2-methylpropyl)carbamoyl]benzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N—((S)-1-carboxy-2-(R)-hydroxypropyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N—((S)-1-carboxybutyl) carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine;1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N—((S)-1-carboxyethyl) ...

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Номер записи: 78
05-07-2018 дата публикации

SELECTIVE CYSTEINE PROTEASE INHIBITORS AND USES THEREOF

Номер: US20180186833A1
Автор: Ahlfors Jan-Eric, Mekouar Khalid
Принадлежит:

The present invention relates to compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteases. Also described are methods where the compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 are used in the prevention and/or treatment of various diseases and conditions in subjects, including cysteine protease-mediated diseases and/or caspase-mediated diseases such as sepsis, myocardial infarction, cancer, tissue atrophy, ischemia, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative diseases such as multiple sclerosis (MS), ALS, Alzheimer's disease, Parkinson's disease, and Huntington's disease). 1administering to a patient, the compound of Formula I:. A method for treating a caspase related disease comprising, a is 0;', 'b is 0;', 'c is 0;', 'd is 0 or 1;', {'sub': 2', '2, 'the line “—” when located between P2 and P3 is a peptide bond or a peptidomimetic bond, wherein when the line “—” is a peptidomimetic bond, the peptidomimetic bond is a bond selected from the group consisting of a CHNH bond, a CO—CHbond, an azapeptide bond, and a retroinverso bond;'}, 'P3 is a natural or non-natural amino acid residue;', 'P2 is alanine, arginine, aspartic acid, asparagine, cysteine, glutamine, isoleucine, histidine, leucine, lysine, methionine, phenylalanine, proline, serine, tryptophan, tyrosine, or a non-natural amino acid residue;', {'sup': 1', '2, 'Rand Rare either in the cis configuration or the trans configuration;'}, 'n is 0, 1, or 3;', {'sup': 4', '5, 'wherein Z is Tetrazol, Cyano, COR, or COR;'}, {'sup': 9', '9', '9', '4', '5', '9', '9', '7', '8', '9', '9', '9', '9', '9, 'sub': 2', '2', '2', '2', '2, 'W is H, alkyl, OH, OR, NH, NHR, NHSOR, halogen, COR, COR, CN, OCOR, OCOR, NO, NO, NRR, NHSOR, NHCOR, SOR, SOR, or SR;'}, 1) H,', {'sup': '3', 'sub': '2', '2) R—CHOC(O ...

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Номер записи: 79
23-07-2015 дата публикации

FLUORINATED EPOXYKETONE-BASED COMPOUNDS AND USES THEREOF AS PROTEASOME INHIBITORS

Номер: US20150203534A1
Автор: Dove Peter, Slassi Abdelmalik
Принадлежит: FLUORINOV PHARMA INC.

The present application relates to novel fluorinated epoxyketone-based compounds, compositions comprising these compounds and their use, in particular for the treatment of diseases, disorders or conditions mediated by proteasome inhibition, in particular, the present application includes compounds of Formula I, and compositions and uses thereof: 35.-. (canceled)8. (canceled)9. The compound of claim 2 , wherein Ris Cheterocycloalkyl and X is Calkylene.10. The compound of claim 9 , wherein Ris selected from morpholinyl claim 9 , 1 claim 9 ,4-oxazepanyl claim 9 , thiomorpholinyl claim 9 , 1 claim 9 ,4-thiazepanyl claim 9 , 1 claim 9 ,4-thiazepanyl-1-oxide claim 9 , 1 claim 9 ,4-thiazepanyl-1 claim 9 ,1-dioxide claim 9 , 1 claim 9 ,4-thiazinanyl-1-oxide claim 9 , 1 claim 9 ,4-thiazinanyl-1 claim 9 ,1-dioxide claim 9 , aziridinyl claim 9 , azetidinyl claim 9 , pyrrolidinyl claim 9 , piperazinyl and 1 claim 9 ,4-diazepanyl.11. (canceled)12. The compound of claim 10 , wherein X is —CH—.13. The compound of claim 1 , wherein Rand Rare each independently selected from the group consisting of Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Calkylene-O—Calkyl claim 1 , Calkylene-O—Chaloalkyl claim 1 , Calkenylene-O—Chaloalkyl and Calkynylene-O—Chaloalkyl claim 1 , wherein at least one of Rand Ris C-alkylene-O—Chaloalkyl.14. The compound of claim 13 , wherein Rand Rare each independently selected from the group consisting of isobutyl claim 13 , —CH—O—CHand —CH—O—CHF claim 13 , wherein at least one of Rand Ris —CH—O—CHF.15. (canceled)16. The compound of claim 13 , wherein Ris selected from the group consisting of Calkyl claim 13 , Calkenyl claim 13 , Calkynyl claim 13 , CalkyleneCcycloalkyl and CalkyleneCaryl.17. (canceled)18. The compound of claim 1 , wherein Ris selected from the group consisting of H and Calkyl.20. The compound of claim 1 , or a salt claim 1 , solvate or prodrug thereof claim 1 , selected from:2-Methyl-thiazole-5-carboxylic acid ((S)-1-{(S)-1-[(S)-1- ...

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Номер записи: 80
23-07-2015 дата публикации

INHIBITION OF GLIADIN PEPTIDES

Номер: US20150203537A1
Автор: Alkan Sefik, Carrasco Rosa A., Durai Malarvizhi, Kitchens Kelly Marie, Poloso Neil, Tamiz Amir
Принадлежит:

Novel compounds and methods for the inhibition of biological barrier permeability and for the inhibition of peptide translocation across biological barriers are identified. Assays for determining modulators of biological barrier permeability and for peptide translocation across biological barriers are provided. Methods for treating diseases relating to aberrant biological barrier permeability and peptide translocation across biological barriers are provided. Such diseases include celiac disease, necrotizing enterocolitis, diabetes, cancer, inflammatory bowel diseases, asthma, COPD, excessive or undesirable immune response, gluten sensitivity, gluten allergy, food allergy, rheumatoid arthritis, multiple sclerosis, immune-mediated or type 1 diabetes mellitus, systemic lupus erythematosus, psoriasis, scleroderma and autoimmune thyroid diseases. 1. A peptide permeability inhibitor consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-162 , wherein said peptide permeability inhibitor inhibits translocation of a gliadin-derived peptide across a biological barrier.2. The peptide of claim 1 , wherein the peptide does not consist of an amino acid sequence selected from the group consisting of SEQ ID NOs: 15 claim 1 , 24 and 25.3. The peptide of claim 1 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5 claim 1 , 10-17 claim 1 , 19-23 claim 1 , 27 claim 1 , 32 claim 1 , 34 claim 1 , 36 claim 1 , 48 claim 1 , 49 claim 1 , 55 claim 1 , 58 claim 1 , 67-77 claim 1 , 79-85 claim 1 , 87 claim 1 , 88 claim 1 , 91 claim 1 , 92 claim 1 , 94 claim 1 , 98-104 claim 1 , 106 claim 1 , 110 claim 1 , 111 claim 1 , 113-125 claim 1 , 127 claim 1 , 128 claim 1 , 147 claim 1 , 150 claim 1 , and 160-162.4. A method of inhibiting gliadin-derived peptide translocation across a biological barrier comprising contacting said barrier with a peptide permeability inhibitor consisting of an amino acid sequence ...

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Номер записи: 81
26-07-2018 дата публикации

Methods for assaying palmitoyl protein thioesterase 1 and tripeptidyl peptidase activity in dried blood spots for detection of neuronal ceroid lipofuscinoses in newborns

Номер: US20180209989A1
Автор: Frantisek Turecek, Michael H. Gelb
Принадлежит: UNIVERSITY OF WASHINGTON

The present disclosure provides assays for lysosomal enzymes, specifically palmitoyl protein thioesterase 1 (PPT1) and tripeptidyl peptidase 1 (TPP1), using, for example, tandem mass spectrometry. The assays involve the detection of enzymatic products obtained through the action of the lysosomal enzymes on new enzyme substrates, and can be used for quantitative enzyme activity measurements. The assays for the enzymes utilize a minimum steps for sample work up and can be run in a simplex format or in a duplex format for the detection of neuronal ceroid lipofuscinoses, or in a multiplex format with other mass spectrometry-based assays for screening of neuronal ceroid lipofuscinoses and other lysosomal storage disorders.

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Номер записи: 82
09-10-2014 дата публикации

Method for the stereoselective preparation of amino acid derivatives

Номер: US20140303344A1
Автор: Antoni RIERA ESCALÉ, Llorenç RAFECAS JANÉ, Monica ALONSO XALMA, Rosario RAMON ALBALATE
Принадлежит: BCN Peptides SA

The invention relates to a process for the stereoselective preparation of amino acid derivatives, comprising a hydrogenation reaction of the compound of formula (III), alternatively its enantiomer, wherein R is (C 1 -C 8 )-alkyl; followed by a hydrolysis reaction to obtain L-mesityl alanine, alternatively its enantiomer D-mesityl alanine and, optionally, subjecting said compound to an amino group protection reaction, particularly as Fmoc. It also comprises Fmoc-L- or Fmoc-D- mesityl alanine as products per se, useful as intermediates in preparing peptides or peptide analogs with therapeutic or biological activity.

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Номер записи: 83
04-08-2016 дата публикации

SUBSTITUTED PHENYLALANINE DERIVATIVES

Номер: US20160222056A1
Автор: ACKERSTAFF Jens, BEYER Kristin, Buchmüller Anja, ELLERMANN Manuel, Gerdes Christoph, HEITMEIER Stefan, HILLISCH Alexander, Röhn Ulrike, Röhrig Susanne, SANDMANN Steffen, Schäfer Martina, SCHMIDT Martina Victoria, SPERZEL Michael, STRASSBURGER Julia, TERJUNG Carsten, Tersteegen Adrian, WEBSTER Robert Alan, WENDT Astrid
Принадлежит: BAYER PHARMA AKTIENGESELLSCHAFT

The invention relates to substituted phenylalanine derivatives and to processes for preparation thereof, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of cardiovascular disorders and/or severe perioperative blood loss. 4. The compound of claim 1 , characterized in that{'sup': '1', 'claim-text': where the 5-membered heterocycle in 2,3-dihydro-1H-benzimidazol-5-yl, 2,3-dihydro-1,3-benzoxazol-5-yl, 1H-benzimidazol-5-yl, 2,3-dihydro-1H-indazol-6-yl, 2,3-dihydro-1,3-benzoxazol-6-yl, 1H-benzimidazol-6-yl and 1H-indazol-6-yl may be substituted by an oxo substituent, and', 'where the benzyl ring in 2,3-dihydro-1H-benzimidazol-5-yl, 2,3-dihydro-1,3-benzoxazol-5-yl, 1H-benzimidazol-5-yl, 2,3-dihydro-1H-indazol-6-yl, 2,3-dihydro-1,3-benzoxazol-6-yl, 1H-benzimidazol-6-yl and 1H-indazol-6-yl may be substituted by a chlorine substituent,, 'Ris 2,3-dihydro-1H-benzimidazol-5-yl, 2,3-dihydro-1,3-benzoxazol-5-yl, 1H-benzimidazol-5-yl, 2,3-dihydro-1H-indazol-6-yl, 2,3-dihydro-1,3-benzoxazol-6-yl, 1H-benzimidazol-6-yl or 1H-indazol-6-yl,'}{'sup': '2', 'claim-text': where ethyl is substituted by a trifluoromethyl substituent, and', {'sub': 1', '3, 'where cyclohexyl is substituted by a substituent selected from the group consisting of hydroxyl, amino and C-C-alkylamino, and'}, {'sub': 1', '4, 'where pyrrolidinyl and piperidinyl may be substituted by 1 to 2 substituents independently selected from the group consisting of oxo, fluorine and C-C-alkyl,'}], 'Ris ethyl, isopropyl, cyclopropyl, cyclobutyl, cyclohexyl, or heterocyclyl bonded via a carbon atom, selected from the group of pyrrolidinyl and piperidinyl,'}{'sup': '3', 'Ris hydrogen,'}{'sup': '4', 'Ris hydrogen or fluorine,'}{'sup': '5', 'Ris methyl,'}or one of the salts thereof, solvates thereof or solvates of the salts thereof.5. The compound of claim 1 , characterized in that{'sup': '1', 'claim-text': where the 5-membered heterocycle in 2,3-dihydro-1H-benzimidazol-5-yl ...

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Номер записи: 84
04-08-2016 дата публикации

COMPOSITION COMPRISING PEPTIDE DERIVED FROM ADIPONECTIN

Номер: US20160222077A1
Автор: HAHN Jang-Hee, LIM Dong-Young
Принадлежит:

Provided is a pharmaceutical or cosmetic composition comprising adiponectin-derived peptide fragments, i.e., the peptides of SEQ ID NOs: 1 to 6 as an active ingredient. The peptides facilitate skin regeneration and moisturization, inhibit skin wrinkle, and have inhibitory activities against allergy and inflammation as well as metastasis of cancer cells. 16.-. (canceled)7. A peptide selected from the group consisting of the peptides of SEQ ID NOs: 1 to 6 , wherein the peptide facilitates the expression of filaggrin and induce the formation of skin barrier , inhibits allergic reactions and inflammatory responses in the skin , or inhibits the metastasis of cancer cells.8. A composition for improving or treating a skin disease , comprising an effective amount of a peptide selected from the group consisting of the peptides of SEQ ID NOs: 1 to 6 , and a pharmaceutically or cosmetically acceptable carrier.9. A method for improving or treating a skin disease , comprising administering to a subject in need thereof an effective amount of a peptide selected from the group consisting of the peptides of SEQ ID NOs: 1 to 6.10. The method of claim 9 , wherein the skin disease is dermatitis claim 9 , skin wrinkle claim 9 , wound claim 9 , or dry skin.11. The method of claim 10 , wherein the dermatitis is one or more selected from the group consisting of allergic dermatitis claim 10 , atopic dermatitis claim 10 , contact dermatitis claim 10 , acne vulgaris claim 10 , ultraviolet radiation-induced dermatitis claim 10 , eczema claim 10 , and psoriasis. The present invention relates to a pharmaceutical or cosmetic composition comprising adiponectin-derived peptide fragments or small peptides. The peptides facilitate skin regeneration and moisturization, inhibit skin wrinkle, and have inhibitory activities against allergy and inflammation as well as metastasis of cancer cells.Wounds, also referred to as skin lesions, show various symptoms, e.g., pain, bleeding, scar formation, ...

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Номер записи: 85
13-08-2015 дата публикации

BENZYLAMINE DERIVATIVES AS INHIBITORS OF PLASMA KALLIKREIN

Номер: US20150225450A1
Автор: DAVIE Rebecca Louise, EDWARDS Hannah Joy, EVANS David Michael, ROOKER David Philip
Принадлежит:

The present invention provides compounds of formula (I): 2. The method of claim 1 , wherein the disease or condition is impaired visual acuity claim 1 , diabetic retinopathy claim 1 , diabetic macular oedema claim 1 , hereditary angioedema claim 1 , diabetes claim 1 , pancreatitis claim 1 , cerebral haemorrhage claim 1 , nephropathy claim 1 , cardiomyopathy claim 1 , neuropathy claim 1 , inflammatory bowel disease claim 1 , arthritis claim 1 , inflammation claim 1 , septic shock claim 1 , hypotension claim 1 , cancer claim 1 , adult respiratory distress syndrome claim 1 , disseminated intravascular coagulation claim 1 , cardiopulmonary bypass surgery claim 1 , or post-operative bleeding from surgery.3. The method of claim 1 , wherein the disease or condition is retinal vascular permeability associated with diabetic retinopathy and diabetic macular oedema.4. The method of claim 1 , wherein Ris phenyl or naphthyl claim 1 , wherein phenyl may be optionally substituted with up to 3 substituents independently selected from alkyl claim 1 , alkoxy claim 1 , OH claim 1 , halo claim 1 , CN claim 1 , COOR claim 1 , CFand NRR.5. The method of claim 1 , wherein Ris phenyl claim 1 , 1-naphthalene claim 1 , 2 claim 1 ,4-dichlorophenyl claim 1 , 3 claim 1 ,4-dichlorophenyl claim 1 , 3 claim 1 ,4-difluorophenyl claim 1 , 4-chlorophenyl claim 1 , 4-trifluoromethylphenyl claim 1 , or 4-ethoxyphenyl.6. The method of claim 1 , wherein Ris H claim 1 , —COaryl claim 1 , —COalkyl claim 1 , —CHCOOH claim 1 , —SOPh claim 1 , or —SOCH.7. The method of claim 1 , wherein Ris —COalkyl or —COaryl.9. The method of claim 1 , wherein Rand Rare independently H or CH.10. The method of claim 1 , wherein the stereochemical configuration about chiral centre *1 is R.11. The method of claim 1 , wherein the stereochemical configuration about chiral centre *2 is S.12. The method of claim 1 , wherein a is 2 and b claim 1 , c claim 1 , d claim 1 , e claim 1 , f claim 1 , g claim 1 , h claim 1 , j claim 1 , 1 ...

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Номер записи: 86
02-08-2018 дата публикации

Chromogenic And Fluorogenic Peptide Substrates For The Detection Of Serine Protease Activity

Номер: US20180215787A1
Автор: Dumitru Arian, Job Harenberg, Roland Kramer
Принадлежит: UNIVERSITAET HEIDELBERG

The present invention relates to chromogenic and fluorogenic substrates that can be used for the highly sensitive and selective detection of the activity of serine proteases. The present invention further relates to methods for the detection of the activity of serine proteases, said methods using the substrates of the present invention. Furthermore, the present invention relates to diagnostic kits and test strips using the above substrates, as well as uses of said substrates.

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Номер записи: 87
11-07-2019 дата публикации

INTRAESOPHAGEAL ADMINISTRATION OF TARGETED NITROXIDE AGENTS FOR PROTECTION AGAINST IONIZING IRRADIATION-INDUCED ESOPHAGITIS

Номер: US20190210969A1
Автор: Epperly Michael W., Gao Xiang, Greenberger Joel S., Li Song, Wipf Peter
Принадлежит: University of Pittsburgh - of the Commonwealth System of Higher Education

Provided herein are compositions and related methods useful for prevention or mitigation of ionizing radiation-induced esophagitis. The compositions comprise compounds comprising a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent or mitigate esophageal damage caused by radiation. 161-. (canceled)73. The method of claim 72 , in which R is Ac claim 72 , Boc claim 72 , Cbz claim 72 , or —P(O)-Ph.74. The method of in which R1 claim 72 , R2 and R3 independently are methyl claim 72 , ethyl claim 72 , propyl claim 72 , 2-propyl claim 72 , butyl claim 72 , t-butyl claim 72 , pentyl claim 72 , hexyl claim 72 , benzyl claim 72 , hydroxybenzyl claim 72 , phenyl and hydroxyphenyl.75. The method of claim 72 , in which R4 is 2 claim 72 ,2 claim 72 ,6 claim 72 ,6-Tetramethyl-4-piperidine 1-oxyl claim 72 , 1-methylazaadamantane N-oxyl) claim 72 , or 1 claim 72 ,1 claim 72 ,3 claim 72 ,3-tetramethylisoindolin-2-yloxyl.79. The method of claim 62 , in which the therapeutic compound is selected from the group consisting of: XJB-5-131 claim 62 , XJB-5-125 claim 62 , XJB-5-197 claim 62 , XJB-7-53 claim 62 , XJB-7-55 claim 62 , XJB-7-75 claim 62 , JP4-049 claim 62 , XJB-5-208 claim 62 , JED-E71-37 claim 62 , JED-E71-58.80. The method of claim 62 , in which the amount effective to prevent or mitigate ionizing irradiation-induced esophagitis in the subject ranges from 0.1 to 100 mg/kg in the subject.81. The method of claim 62 , in which the therapeutic compound is administered between 30 minutes and one hour after radiation exposure in the subject.82. The method of claim 62 , in which the therapeutic compound is administered prior to radiation exposure in the subject.83. The method of claim 62 , wherein the subject is susceptible to claim 62 , or has claim 62 , ...

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Номер записи: 88
11-07-2019 дата публикации

COMPOUNDS FOR PROTEASOME ENZYME INHIBITION

Номер: US20190211058A1
Автор: LAIDIG Guy J., SMYTH Mark S.
Принадлежит:

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. 2. A compound of claim 1 , wherein X is O.3. A compound of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , and Rare independently selected from Calkyl claim 2 , Chydroxyalkyl claim 2 , and Caralkyl; and Ris hydrogen.4. A compound of claim 3 , wherein Rand Rare independently Caralkyl and Rand Rare independently Calkyl.5. A compound of claim 4 , wherein R claim 4 , R claim 4 , R claim 4 , and Rare all hydrogen.6. A compound of claim 5 , wherein Y is selected from N-alkyl claim 5 , O claim 5 , and CH.7. A compound of claim 6 , wherein Z is CH claim 6 , and m and n are both 0.8. A compound of claim 6 , wherein Z is CH claim 6 , m is O claim 6 , and n is 2 or 3.9. A compound of claim 6 , wherein Z is O claim 6 , m is 1 claim 6 , and n is 2.17. A compound of claim 16 , wherein X is O.18. A compound of claim 17 , wherein R claim 17 , R claim 17 , R claim 17 , and Rare independently selected from Calkyl claim 17 , Chydroxyalkyl claim 17 , and Caralkyl.19. A compound of claim 18 , wherein Rand Rare independently Caralkyl and Rand Rare independently Calkyl.21. A compound of claim 20 , wherein X is O.22. A compound of claim 21 , wherein Rand Rare independently selected from Calkyl claim 21 , Chydroxyalkyl claim 21 , and Caralkyl.23. A compound of claim 22 , wherein Rand Rare independently Calkyl.24. A compound ...

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Номер записи: 89
11-08-2016 дата публикации

NOVEL INHIBITORS OF MAMMALIAN TIGHT JUNCTION OPENING

Номер: US20160228488A1
Автор: Tamiz Amir
Принадлежит:

The present invention provides novel peptides that inhibit and/or reduce the opening of mammalian tight junctions, i.e. peptide tight junction antagonists. The present invention also provides methods for the treatment of excessive or undesirable permeability of a tissue by administering to a subject suffering from such a condition a composition comprising a peptide tight junction antagonist of the invention. 1. A peptide tight junction antagonist , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-69.2. The peptide tight junction antagonist of claim 1 , wherein the peptide is eight to ten amino acids in length.3. The peptide tight junction antagonist of claim 1 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11 claim 1 , 13 claim 1 , 17 claim 1 , 18 claim 1 , 20-32 claim 1 , 34 claim 1 , 35 claim 1 , 54 claim 1 , 57 claim 1 , and 67-69.4. The peptide tight junction antagonist of claim 1 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-69.5. The peptide tight junction antagonist of claim 1 , wherein the peptide consists essentially of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11 claim 1 , 13 claim 1 , 17 claim 1 , 18 claim 1 , 20-32 claim 1 , 34 claim 1 , 35 claim 1 , 54 claim 1 , 57 claim 1 , and 67-69.6. The peptide tight junction antagonist of claim 1 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-69.7. The peptide tight junction antagonist of claim 1 , wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-11 claim 1 , 13 claim 1 , 17 claim 1 , 18 claim 1 , 20-32 claim 1 , 34 claim 1 , 35 claim 1 , 54 claim 1 , 57 claim 1 , and 67-69.8. A method of treating an excessive or undesirable permeability of a tissue containing tight junctions ...

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Номер записи: 90
20-08-2015 дата публикации

Bortezomib Esters And Formulations Thereof

Номер: US20150232508A1
Автор: BERARDI Giorgio, Brandi Paolo, Ciambecchini Umberto, DE SIO Vincenzo, TURCHETTA Stefano, ZENONI Maurizio
Принадлежит:

Bortezomib esters with tartaric acid wherein the molar ratio between bortezomib and tartaric acid is 2:1 and formulations containing them are described. 1) An ester of bortezomib with tartaric acid wherein bortezomib and tartaric acid are in molar ratio 2:1.3) Crystalline and amorphous forms of a compound according to .4) An ester according to claim 1 , wherein tartaric acid is L-tartaric acid.5) Formulations containing an ester of bortezomib according to in admixture with pharmaceutically acceptable excipients.6) Formulations according to in liquid form.7) Injectable solutions obtained by reconstitution of a formulation according to with physiologically compatible solutions. The present invention relates to bortezomib esters, more particularly to bortezomib esters with tartaric acid, and to stable formulations containing them.The active ingredient bortezomib, the chemical compound of formula Iis a dipeptide wherein one of the two amino acids is an aminoboronic acid. Bortezomib belongs to the therapeutic class of proteasome inhibitors, a cellular protein complex having the function of degrading the proteins to be eliminated. The inhibitory effect of bortezomib on proteasome interferes with the intracellular processes for protein turnover, with the consequent beginning of a degenerative state of the cell leading to its death. For this pharmacological action bortezomib has been approved for the treatment of forms of multiple myeloma which were already treated with at least another therapeutic agent.The active ingredient is on the market under the tradename Velcade® as lyophilized powder containing mannitol esters of bortezomib which is administered by intravenous route after reconstitution of the lyophilizate with physiologic solution where the active ingredient is reconstituted by hydrolysis.Bortezomib was first described in U.S. Pat. No. 5,780,454 with the code MG-341. The compound is isolated as trimeric boroxine of formula (II)as described in U.S. Pat. No. 6,699, ...

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Номер записи: 91
23-10-2014 дата публикации

AMORPHOUS EZATIOSTAT ANSOLVATE

Номер: US20140315812A1
Автор: Schow Steven R.
Принадлежит:

Provided herein is an amorphous form of a pharmaceutically acceptable salt of ezatiostat, for example, ezatiostat hydrochloride, compositions, uses and methods of preparation thereof. 1. A pharmaceutically acceptable salt of amorphous ezatiostat.2. A pharmaceutically acceptable salt of amorphous ezatiostat , which is an ansolvate.3. A pharmaceutically acceptable salt of amorphous ezatiostat , which is ezatiostat hydrochloride exhibiting stability of at least 8 months.4. The pharmaceutically acceptable salt of amorphous ezatiostat of claim 3 , which is an ansolvate.5. The pharmaceutically acceptable salt of amorphous ezatiostat of claim 3 , having an X-ray powder diffraction pattern that is substantially the same as .6. The pharmaceutically acceptable salt of amorphous ezatiostat of claim 3 , having a differential scanning calorimetry that is substantially the same as .76. A composition comprising the pharmaceutically acceptable salt of amorphous ezatiostat of any one of -.86. A method of treating severe chronic idiopathic neutropenia comprising administering a therapeutically effective amount of the pharmaceutically acceptable salt of amorphous ezatiostat of any one of - claims 1 , or the composition of to a patient in need of such treatment.96. A method of treating leukemia comprising administering a therapeutically effective amount of the pharmaceutically acceptable salt of amorphous ezatiostat of any one of - claims 1 , or the composition of to a patient in need of such treatment.106. A method of treating multiple myeloma comprising administering a therapeutically effective amount of the pharmaceutically acceptable salt of amorphous ezatiostat of any one of - claims 1 , or the composition of to a patient in need of such treatment.116. A method of treating a myelodysplastic syndrome comprising administering a therapeutically effective amount of the pharmaceutically acceptable salt of amorphous ezatiostat of any one of - claims 1 , or the composition of to a ...

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Номер записи: 92
27-08-2015 дата публикации

INHIBITORS OF PROTEIN TYROSINE PHOSPHATASES

Номер: US20150239931A1
Автор: Zhang Sheng, ZHANG Zhong-Yin
Принадлежит:

Novel protein tyrosine phosphatase (PTP) inhibitor compounds synthesized from phosphonodifluoromethyl phenylalanine (F2Pmp) are provided. Use of these compounds for inhibiting a PTP enzyme (such as PTP-MEG2), as well as treating a disease, disorder, or condition associated with inappropriate activity of a PTP (such as type 2 diabetes), is also provided. 2. The compound according to claim 1 , wherein Rand Rare the same or different and each individually is an acyl group of a benzoic acid claim 1 , the benzoic acid being optionally substituted with one or more moieties selected from the group consisting of halogen claim 1 , hydroxyl claim 1 , C-Calkyl claim 1 , and C-Calkoxy claim 1 , and wherein Ris an acyl group of a phenylacetic acid claim 1 , the phenylacetic acid being optionally substituted with one or more moieties selected from the group consisting of halogen claim 1 , hydroxyl claim 1 , C-Calkyl claim 1 , and C-Calkoxy.4. A method for treating a disease claim 1 , disorder claim 1 , or condition associated with inappropriate activity of a protein tyrosine phosphatase in an individual claim 1 , the method comprising administering to the individual the compound of .5. The method according to claim 4 , wherein the disease claim 4 , disorder claim 4 , or condition is selected from the group consisting: of type 1 diabetes claim 4 , type 2 diabetes claim 4 , obesity claim 4 , metabolic syndrome claim 4 , Crohn's disease claim 4 , rheumatoid arthritis claim 4 , Graves' disease claim 4 , systemic lupus erythematosus claim 4 , leukemia claim 4 , and tuberculosis6. The method according to claim 4 , wherein the compound is Compound 7 claim 4 , a therapeutically suitable prodrug thereof claim 4 , or a therapeutically suitable salt thereof.7. The method according to claim 6 , wherein the disease claim 6 , disorder claim 6 , or condition is type 2 diabetes.8. A method of manufacturing a medicament for the treatment of a disease claim 1 , disorder claim 1 , or condition ...

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Номер записи: 93
17-08-2017 дата публикации

PEPTIDE MACROCYCLES AGAINST ACINETOBACTER BAUMANNII

Номер: US20170233437A1
Автор: Alanine Alexander, Beignet Julien, Bleicher Konrad, Fasching Bernhard, Hilpert Hans, Hu Taishan, Jackson Stephen, Kolczewski Sabine, Kroll Carsten, MacDonald Dwight, Schaeublin Adrian, Shen Hong, Stoll Theodor, Thomas Helmut, Wahhab Amal, Zampaloni Claudia
Принадлежит: Hoffmann-La Roche Inc.

The present invention provides compounds of formula (I) 3. The compound according to any of or , wherein:{'sup': 1', '1, 'Xis CRor N,'}{'sup': 2', '12, 'Xis CRor N,'}{'sup': 3', '13, 'Xis CRor N,'}{'sup': 4', '14', '1', '2', '3', '4, 'Xis CRor N, with the proviso that not more than two of X, X, Xand Xare N;'}{'sup': 5', '15, 'Xis CRor N,'}{'sup': 6', '16, 'Xis CRor N,'}{'sup': 7', '17, 'Xis CRor N,'}{'sup': 8', '18', '5', '6', '7', '8, 'Xis CRor N, with the proviso that not more than two of X, X, Xand Xare N;'}{'sup': '1', 'sub': 2', 'm', '2', 'm', '1-7', '1-7', '3-7', '1-7, 'Ris —(CH)-heteroaryl or —(CH)— heterocycloalkyl; wherein heteroaryl is optionally substituted with one or more halo, cyano, C-alkyl, C-haloalkyl, C-cycloalkyl or C-alkoxy; and wherein heterocycloalkyl is partly unsaturated;'}{'sup': 2', '4', '6, 'sub': 1-7', '1-7', '3-7, 'R, Rand Rare each individually selected from hydrogen, C-alkyl, C-haloalkyl, and C-cycloalkyl;'}{'sup': 3', '20', '21', '20', '21', '20', '21, 'sub': 1-7', '2', 'n', '2', 'n', '2', 'n', '2', 'q, 'Ris —C-alkyl, —(CH)—NRR, —(CH)—C(O)NRRor —(CH)—O—(CH)—NRR;'}{'sup': 5', '22', '23', '22', '23, 'sub': 1-7', '1-7', '2', 'o', '2', 'o, 'claim-text': [{'sub': 2', 'o', '2', 'q', '2', 'o', '2', 'o, 'sup': 20', '21', '22', '23', '22', '23, '—(CH)—O—(CH)NRR, —(CH)—NH—C(NH)—NRR, —(CH)—NH—C(O)—NRR,'}, {'sub': 2', 'o', '2', 'o', '2', 'o', '2', 'o, 'sup': '26', '—(CH)—NH—C(O)—OR, —(CH)-heterocycloalkyl, —(CH)-heteroaryl, —(CH)-aryl,'}, {'sub': 1-7', '1-7', '1-7, 'wherein cycloalkyl, heterocycloalkyl, heteroaryl and aryl are optionally substituted by halo, cyano, C-alkyl, C-haloalkyl, C-alkoxy or aryl;'}], 'Ris hydrogen, C-alkyl, hydroxy-C-alkyl, —(CH)—NRR, —(CH)—C(O)—NRR,'}{'sup': 7', '8, 'sub': 1-7', '1-7', '3-7', '1-7, 'Rand Rare each individually selected from hydrogen, C-alkyl, C-haloalkyl, C-cycloalkyl and C-alkoxy;'}{'sup': 11', '12', '13', '14', '15', '16', '24', '25', '24', '25, 'sub': 1-7', '1-7', '1-7', '1-7', '1-7', '2', '3-7, ' ...

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Номер записи: 94
25-07-2019 дата публикации

INHIBITORS OF IAP

Номер: US20190224269A1
Автор: Cohen Frederick, Flygare John A., Gazzard Lewis J., Tsui Vickie Hsiao-Wei
Принадлежит: Genentech, Inc.

Novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies and have the general formula I: 2. The compound of which is (S)-1-[(S)-2-cyclohexyl-2-((S)-2-methylamino-propionylamino)-acetyl]-pyrrolidine-2-carboxylic acid (2-oxazol-2-yl-4-phenyl-thiazol-5-yl)-amide (Ia) or a pharmaceutically acceptable salt thereof.3. A compound of wherein R-Rare each independently H or methyl.4. A compound of wherein Ris cyclohexyl.5. A compound of wherein Ris cyclohexyl.6. A compound of wherein one of Rand Ris H and the other is methyl; or Ris methyl; or Rand Rare each H.7. A method for inhibiting the binding of an TAP protein to a caspase protein comprising contacting said TAP protein with a compound of .8. A method for treating a disease or condition associated with the overexpression of an TAP in a mammal claim 1 , comprising administering to said mammal an effective amount of a compound of .9. A method of inducing apoptosis in a cell comprising introducing into said cell a compound of .10. A method of sensitizing a cell to an apoptotic signal comprising introducing into said cell a compound of .11. The method of claim 10 , wherein said apoptotic signal is induced by contacting said cell with a compound selected from the group consisting of cytarabine claim 10 , fludarabine claim 10 , 5-fluoro-2′-deoxyuiridine claim 10 , gemcitabine claim 10 , methotrexate claim 10 , bleomycin claim 10 , cisplatin claim 10 , cyclophosphamide claim 10 , adriamycin (doxorubicin) claim 10 , mitoxantrone claim 10 , camptothecin claim 10 , topotecan claim 10 , colcemid claim 10 , colchicine claim 10 , paclitaxel claim 10 , vinblastine claim 10 , vincristine claim 10 , tamoxifen claim 10 , finasteride claim 10 , docetaxel and mitomycin C.12. The method of claim 10 , wherein said apoptotic signal is induced by contacting said cell with Apo2L/TRAIL.13. A method for treating cancer claim 1 , comprising administering to said mammal an effective amount of a compound of .14. A ...

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Номер записи: 95
25-08-2016 дата публикации

ANTI-INFLAMMATORY TRIPEPTIDES

Номер: US20160244484A1
Автор: Abels Christoph, Knie Ulrich, Soeberdt Michael
Принадлежит:

The present invention relates to tripeptide compounds according to the general formula (1) and their use as a medicament, in particular as anti-inflammatory agents. 2. The tripeptide compound according to claim 1 ,wherein in general formula (1):{'sup': 1', 'α', 'α', 'α, 'AAis selected from α-amino acids, N-methyl amino acids and N, N-dimethyl amino acids; and'}{'sup': '2', 'AAis selected from α-aminoisobutyric acid, t-butyl glycine, α-aminoisobutyric acid amide and t-butyl glycine amide,'}orwherein:{'sup': 1', 'α', 'α', 'α, 'AAis selected from α-amino acids, N-methyl amino acids and N, N-dimethyl amino acids; and'}{'sup': 2', 'α', 'α, 'AAis selected from N-methyl amino acids and N-methyl amino acid amides.'}4. The tripeptide compound according to claim 1 , wherein in general formula (1) and/or general formula (2):{'sup': 1', 'α', 'α, 'AAis an N, N-dimethyl amino acid;'}{'sup': 2', 'α, 'AAis an N-methyl amino acid.'}5. The tripeptide compound according to claim 1 , wherein in the definition of AAthe N-methyl amino acids and N claim 1 , N-dimethyl amino acids are selected from the group consisting of N-methyl-1-Nal claim 1 , N claim 1 ,N-dimethyl-1-Nal claim 1 , N-methyl-2-Nal claim 1 , N claim 1 ,N-dimethyl-2-Nal claim 1 , N-methyl-Abu claim 1 , N claim 1 ,N-dimethyl-Abu claim 1 , N-methyl-Ala claim 1 , N claim 1 ,N-dimethyl-Ala claim 1 , N-methyl-Arg claim 1 , N claim 1 ,N-dimethyl-Arg claim 1 , N-methyl-Asn claim 1 , N claim 1 ,N-dimethyl-Asn claim 1 , N-methyl-Cha claim 1 , N claim 1 ,N-dimethyl-Cha claim 1 , N-methyl-Cit claim 1 , N claim 1 ,N-dimethyl-Cit claim 1 , N-methyl-Cys claim 1 , N claim 1 ,N-dimethyl-Cys claim 1 , N-methyl-Dab claim 1 , N claim 1 ,N-dimethyl-Dab claim 1 , N-methyl-Dap claim 1 , N claim 1 ,N-dimethyl-Dap claim 1 , Sar claim 1 , N claim 1 ,N-dimethyl-Gly claim 1 , N-methyl-His claim 1 , N claim 1 ,N-dimethyl-His claim 1 , N-methyl-Hle claim 1 , N claim 1 ,N-dimethyl-Hle claim 1 , N-methyl-Homophe claim 1 , N claim 1 ,N-dimethyl-Homophe ...

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Номер записи: 96
24-08-2017 дата публикации

GADD45BETA/MKK7 INHIBITOR FOR THE TREATMENT OF A RESISTANT HAEMATOLOGICAL MALIGNANCY

Номер: US20170240592A1
Автор: "DANDREA Daniel", BEGALLI Federica, Franzoso Guido, Tornatore Laura
Принадлежит:

A Gadd45β/MKK7 inhibitor for use in a method of treating a resistant haematological malignancy, combinations of said inhibitor with a further anti-cancer agent and related methods of use. 168.-. (canceled)69. A method of treating a resistant haematological malignancy in a subject , the method comprising administering a therapeutically effective amount of a Gadd45β/MKK7 inhibitor to the subject.72. The method of claim 69 , wherein the resistant haematological malignancy is multiple myeloma which is resistant to treatment with an anti-cancer agent selected from the group consisting of a proteasome inhibitor claim 69 , an IMiD anti-cancer agent and a glucocorticoid claim 69 , or is resistant to treatment with bortezomib claim 69 , or one or more of lenalidomide claim 69 , thalidomide and pomalidomide claim 69 , or dexamethasone.73. The method of claim 69 , wherein the resistant haematological malignancy is diffuse large B-cell lymphoma (DLBCL) which is resistant to treatment with an anti-cancer agent selected from the group consisting of an anti-CD20 agent claim 69 , a cytotoxic agent claim 69 , an anthracycline antibiotic anti-cancer agent claim 69 , a mitotic inhibitor claim 69 , a glucocorticoid and a Bruton's tyrosine kinase inhibitor.74. The method of claim 72 , wherein the resistant haematological malignancy is diffuse large B-cell lymphoma (DLBCL) which is resistant to treatment with rituximab claim 72 , or cyclophosphamide claim 72 , or doxorubicin claim 72 , or vincristine claim 72 , or prednisone claim 72 , or ibrutinib.75. The method of claim 69 , wherein the resistant haematological malignancy is Hodgkin's Lymphoma which is resistant to treatment with an anti-cancer agent claim 69 , or vincristine claim 69 , or doxorubicin claim 69 , or dexamethasone claim 69 , or bleomycin claim 69 , or etoposide.76. The method of claim 69 , wherein the Gadd45β/MKK7 inhibitor administered in combination with another anti-cancer agent.77. The method of further comprising: ...

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Номер записи: 97
01-08-2019 дата публикации

SELF-ASSEMBLING PEPTIDE POLYMER

Номер: US20190233473A1
Автор: Bettinger Christopher, Lampel Ayala, McPhee Scott, Scott Gary, Tuttle Tell, Ulijn Rein V.
Принадлежит:

A self-assembling peptide is provided that is enzymatically oxidized to form a polymeric pigment. The monomeric peptide has three amino acids (tyrosine (Y), one phenylalanine (F), and one aspartic acid (D) or one lysine (K)) and, following self-assembly and treatment with a tyrosinase enzyme oxidizes and polymerizes into a material with predetermined properties. 1. A polymeric peptide pigment comprising:a polymerized peptide that is the reaction product of oxidizing a plurality of peptides, wherein each peptide consists of three amino acids including one tyrosine (Y), one phenylalanine (F), and either one aspartic acid (D) or one lysine (K), wherein the tyrosine and the phenylalanine are adjacent one another.2. A polymeric peptide pigment formed by a method comprising sequential steps of:forming an aqueous solution of a peptide consisting of three amino acids including one tyrosine (Y), one phenylalanine (F), and either one aspartic acid (D) or one lysine (K), wherein the tyrosine and the phenylalanine are adjacent one another;annealing by heating and subsequently cooling the aqueous solution to less than 30° C., wherein the peptides self-assemble to form a supramolecular structure;oxidizing the peptide to initiate a polymerization reaction, the polymerization reaction forming a polymeric peptide pigment.3. The polymeric peptide pigment as recited in claim 2 , wherein the peptide has a C terminus that is capped with an amide.4. The polymeric peptide pigment as recited in claim 2 , wherein the step of oxidizing uses an enzymatic oxidation.5. The polymeric peptide pigment as recited in claim 4 , wherein the enzymatic oxidation is performed using a tyrosinase.6. The polymeric peptide pigment as recited in claim 2 , wherein the peptide is YFD.7. The polymeric peptide pigment as recited in claim 6 , wherein the polymeric peptide pigment is an opaque gel.8. The polymeric peptide pigment as recited in claim 2 , wherein the peptide is FYD.9. The polymeric peptide pigment as ...

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Номер записи: 98
13-11-2014 дата публикации

IAP BIR Domain Binding Compounds

Номер: US20140336134A1
Автор: Boudreault Alain, Bureau Patrick, Gillard John W., Jaquith James, Laurent Alain
Принадлежит: PHARMASCIENCE INC.

A compound of Formula I 2. The compound claim 1 , according to claim 1 , wherein the compound is a pharmaceutically acceptable salt of Formula I.3. The compound claim 1 , according to claim 1 , wherein the compound is an HCl salt of Formula I.6. The compound claim 2 , according to claim 2 , in which Rand Rare both CH.7. The compound claim 2 , according to claim 2 , in which Rand Rare both C(CH).12. The compound claim 2 , according to claim 2 , in which Q and Qare both NRR.13. The compound claim 2 , according to claim 2 , in which A and Aare both CH.14. The compound claim 2 , according to claim 2 , in which A and Aare both C═O.15. The compound claim 2 , according to claim 2 , in which A and Aare both C═O claim 2 , and Q and Qare both NRR claim 2 , wherein Ris H and{'sup': '5', 'claim-text': [{'sub': 1', '6, '1) C-Calkyl,'}, {'sub': 2', '6, '2) C-Calkenyl,'}, {'sub': 2', '4, '3) C-Calkynyl,'}, {'sub': 3', '7, '4) C-Ccycloalkyl,'}, {'sub': 3', '7, '5) C-Ccycloalkenyl,'}, '6) aryl,', '7) heteroaryl,', '8) heterocyclyl, or', '9) heterobicyclyl,, 'Ris'}{'sup': 6', '10, 'wherein the alkyl, alkenyl, alkynyl, cycloalkyl, and cycloalkenyl are optionally substituted with one or more Rsubstituents; and wherein the aryl, heteroaryl, heterocyclyl, and heterobicyclyl are optionally substituted with one or more Rsubstituents.'}17. The compound claim 13 , according to claim 13 , wherein Q and Qare NRR.20. The compound claim 14 , according to claim 14 , wherein Q and Qare NRR.22. The compound claim 21 , according to claim 21 , wherein Ris C-Calkyl optionally substituted with one or more Rsubstituents or aryl optionally substituted with one or more Rsubstituents.32. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier claim 2 , diluent or excipient. This patent application is a divisional of copending U.S. patent application Ser. No. 13/672,637, filed Nov. 8, 2012, which is a divisional of U.S. patent application Ser. No. 12/619,979, filed ...

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Номер записи: 99
31-08-2017 дата публикации

SELF-ASSEMBLING TRIPEPTIDES

Номер: US20170246237A1
Автор: ABUL-HAIJA Yousef, FREDERIX Pim, Scott Gary, Tuttle Tell, ULIJN Rein
Принадлежит:

The present invention relates to a method of predicting the propensity of tripeptides to from aggregates in solution. The present invention also provides tripeptides which are able to form aggregates in solution, as well as uses thereof. The present invention also provides nanostructures formed by self-aggregation of tripeptides of the present invention. The present invention also provides pH responsive aggregates as well as methods of screening for the ability of a tripeptide to form a pH dependent aggregate or gel. 1. A solution comprising a self-aggregated tripeptide , the tripeptide having the formula:{'br': None, 'sub': 1', '2', '3, 'A-A-A'}wherein{'sub': '1', 'Ais a hydrogen bond donating amino acid, such as K, R, S, T, or P, H, or W, or F;'}{'sub': '2', 'Ais an aromatic amino acid, such as F, Y, W, or H;'}{'sub': '3', 'Ais an aromatic amino acid, such as F, Y, or W, or a negatively charged amino acid such as D or E.'}2. The solution according to wherein claim 1 , the tripeptide has the formula;{'br': None, 'sub': 1', '2', '3, 'A-A-A'}wherein{'sub': '1', 'Ais K, R, S, T or P;'}{'sub': '2', 'Ais F, Y, or W;'}{'sub': '3', 'Ais F, Y, W, D or E.'}3. A solution comprising a self-aggregated tripeptide claim 1 , wherein the tripeptide is identified in Table 2.4. The solution according to any of - wherein the peptide displays a hydrophilicity-adjusted measure of propensity for aggregation (AP) value of >0.10 claim 1 , 0.11 claim 1 , 0.12 claim 1 , 0.13 claim 1 , 0.14 claim 1 , 0.15 claim 1 , 0.16 claim 1 , 0.17 claim 1 , or 0.18.5. The solution according to wherein the tripeptide displays a propensity of aggregation (AP) value of <2.0.6. The solution according to any of - selected from KYF claim 4 , KFF claim 4 , KYW KYY and FFD claim 4 , or KYF claim 4 , KFF claim 4 , KYW and KYY.7. The solution according to any - wherein the self-aggregated excludes the peptides CFF claim 4 , FFF claim 4 , VFF claim 4 , FFV claim 4 , LFF claim 4 , VYV claim 4 , KFG or DFN.8. A self- ...

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Номер записи: 100