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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 3344. Отображено 100.
12-04-2012 дата публикации

Inhibitors of protein tyrosine phosphatases

Номер: US20120088720A1
Автор: Sheng Zhang, Zhong-Yin Zhang
Принадлежит: Indiana University Research And Technology Corp

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.

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Номер записи: 1
12-04-2012 дата публикации

Compounds for enzyme inhibition

Номер: US20120088762A1
Автор: Catherine Sylvain, Francesco Parlati, Guy J. Laidig, Han-Jie Zhou, Kevin D. Shenk, Mark K. Bennett, Mark S. Smyth
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.

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Номер записи: 2
21-03-2013 дата публикации

Sulfur-Containing Amino Acid Derivative

Номер: US20130071863A1
Автор: Kubota Kazuyuki, Mizukoshi Toshimi
Принадлежит: AJINOMOTO CO., INC.

The present invention provides a method of measuring an endogenous low-molecular-weight compound specifically and conveniently with high sensitivity. Using the particular sulfur-containing amino acid derivative, a method of measuring an endogenous low-molecular-weight compound specifically and conveniently with high sensitivity can be provided. 2. The derivative according to claim 1 , wherein Y is a group bound to an endogenous low-molecular-weight compound claim 1 , and Z is selected from the group consisting of a hydrogen atom and a high-molecular-weight-imparting group.3. The derivative according to claim 1 , wherein Y is an endogenous low-molecular-weight compound reactive group claim 1 , and Z is a labeling compound modifying group.4. The derivative according to claim 1 , wherein the immunoresponsive hydrophobic group has a cyclic structure.5. The derivative according to claim 4 , wherein the immunoresponsive hydrophobic group is selected from the group consisting of a 9-fluorenylmethyloxycarbonyl (Fmoc) group and a quinolinylaminocarbonyl group.6. The derivative according to claim 1 , wherein the endogenous low-molecular-weight compound reactive group is selected from the group consisting of an aldehyde group claim 1 , an N-succinimidyl group claim 1 , a halogen group claim 1 , an isothiocyanate group claim 1 , and a maleimido group.7. The derivative according to claim 1 , wherein the high-molecular-weight-imparting group or labeling compound modifying group is bound via a linker.8. A reagent for measuring an endogenous low-molecular-weight compound claim 1 , which comprises the sulfur-containing amino acid derivative according to .9. The reagent according to claim 8 , wherein the endogenous low-molecular-weight compound is an amino acid.10. A method of producing an antibody which is able to recognize an endogenous low-molecular-weight compound claim 2 , comprising immunizing an animal with an antigen comprising the sulfur-containing amino acid derivative ...

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Номер записи: 3
04-07-2013 дата публикации

Cysteine protease inhibitors

Номер: US20130172232A1
Автор: Björn Klasson, Daniel Jonsson, Daniel Wiktelius, Ellen Hewitt, Jan Tejbrant, Pia Kahnberg, Stina Lundgren, Susana Ayesa, Urszula Grabowska
Принадлежит: Medivir UK Ltd

Compounds of the formula I wherein R 2a and R 2b are independently H, halo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkoxy, or R 2a and R 2b together with the carbon atom to which they are attached form a C 3 -C 6 cycloalkyl; R 3 is a C 5 -C 10 alkyl, optionally substituted with 1-3 substituents independently selected from halo, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; or R 3 is a C 2 -C 4 alkyl chain with at least 2 chloro or 3 fluoro substituents; or R 3 is C 3 -C 7 cycloalkylmethyl, optionally substituted with 1-3 substituents independently selected from C 1 -C 4 alkyl, halo, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; R 4 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylamino, C 1 -C 6 dialkylamino or; R 4 is Het or Carbocyclyl, either of which is optionally substituted with 1-3 substituents R 4 is Het, carbocyclyl, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 haloalkoxy; n is 1, 2 or 3; for the use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

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Номер записи: 4
18-07-2013 дата публикации

THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE

Номер: US20130184222A1
Автор: Popovici-Muller Janeta, Salituro Francesco G., Saunders Jeffrey, Travins Jeremy, Yan Shunqi
Принадлежит: AGIOS PHARMACEUTICALS, INC

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1 comprising administering to a subject in need thereof a compound described here. 2. The compound of claim 1 , wherein Ris 3-fluorophenyl.3. The compound of or claim 1 , wherein:{'sup': '1', 'Ris selected from cyclohexyl, cyclopentyl, cycloheptyl, 3,3-difluorocyclobutyl, 4,4,-difluorocyclohexyl, and bicyclo[2.2.1]heptanyl; and'}{'sup': '4', 'Ris selected from 1-(methylmethoxycarbonylamino)ethyl, 1,2,3,4-tetrahydroquinolin-1-yl, 1-ethoxycarbonylpiperidin-2-yl, 1-ethoxycarbonylpyrrolidin-2-yl, 1H-benzimidazol-1-ylmethyl, 1H-indazol-3-ylmethyl, indolin-1-ylmethyl, 1H-indol-3-ylmethyl, 1H-indol-5-ylmethyl, 1H-pyrrolo[2,3-b]pyridine-3-ylmethyl, 1H-pyrrolo[3,2-b]pyridin-3-ylmethyl, 1-methoxycarbonylpiperidin-2-yl, 1-methoxycarbonylpyrrolidin-2-yl, 2-fluoropyridin-3-ylaminomethyl, 2-imino-4-fluoropyridin-1-ylmethyl, 2-methoxyphenylaminomethyl, 2-methyl-1H-benzimidazol-1-ylmethyl, 2-methylimidazol-1-ylmethyl, 2-trifluoromethyl-1H-imidazol-1-yl, 3-cyanophenylaminomethyl, 3-fluoropyridin-2-ylaminomethyl, 3-methoxyphenylaminomethyl, 4-(1,3,4-oxadiazole-2-yl)phenylaminomethyl, 4-(dimethylaminocarbonyloxy)phenylmethyl, 4,5-dichloroimidazol-1-ylmethyl, 4-cyanophenylaminomethyl, 4-fluorophenylaminomethyl, 4-fluoropyridin-2-ylaminomethyl, 4-hydroxyphenylmethyl, 4-methoxycarbonylmorpholin-3-yl, 4-methoxycarbonylpiperazin-1-ylmethyl, 4-methoxyphenylaminomethyl, 4-methylcarbonyloxyphenylmethyl, 5-fluoropyridin-2-aminomethyl, 5-fluoropyridin-2-oxymethyl, 6-fluoropyridin-3-ylaminomethyl, benzomorpholin-4-ylmethyl, methoxycarbonylaminomethyl, methylmethoxycarbonylaminomethyl, methylphenylaminomethyl, phenylaminomethyl, pyridin-2-oxymethyl, pyridin-2-ylaminomethyl, pyridin-2-yloxymethyl, pyridin-3-oxymethyl, pyridin-3-ylmethyl, pyridin-4-ylmethyl, thiazol-4-ylmethyl, and thien-2-ylmethyl.'}4. The compound of claim 1 , wherein the compound is selected from any one of Compound numbers 104 claim ...

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Номер записи: 5
18-07-2013 дата публикации

Modulations of protease activated receptors

Номер: US20130184226A1
Автор: David Paul Fairlie, Jacky Yung Suen, Ligong Liu, Mei Kwan Yau
Принадлежит: University of Queensland UQ

The present invention provides novel compounds of the Formula (1), 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-2 (PAR2) and for treating a subject at risk of—or susceptible to—a disease or disorder, or having a disease or disorder associated with undesirable PAR2 activity.

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Номер записи: 6
25-07-2013 дата публикации

THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE

Номер: US20130190249A1
Автор: Cai Zhenwei, Cui Dawei, Lemieux Rene M., Popovici-Muller Janeta, Travins Jeremy, ZHOU Ding
Принадлежит: AGIOS PHARMACEUTICALS, INC

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 or claim 1 , wherein each Rand Ris independently aryl optionally substituted with one to three Rgroups.54. The compound of any one of - claims 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 ...

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Номер записи: 7
15-08-2013 дата публикации

Compositions Comprising Enzyme-Cleavable Prodrugs of Active Agents and Inhibitors Thereof

Номер: US20130210854A1
Автор: Craig O. Husfeld, Jonathan W. Wray, Julie D. Seroogy, Thomas E. Jenkins
Принадлежит: Signature Therapeutics Inc

The present disclosure provides pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a prodrug that provides enzymatically-controlled release of a drug and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the drug from the prodrug so as to attenuate enzymatic cleavage of the prodrug. The disclosure provides pharmaceutical compositions which comprise an enzyme inhibitor and a prodrug that contains an enzyme-cleavable moiety that, when cleaved, facilitates release of the drug.

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Номер записи: 8
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: 9
12-09-2013 дата публикации

Lipoyl Compounds And Their Use for Treating Ischemic Injury

Номер: US20130237483A1
Автор: Alan S. Lader, Alexander B. Baguisi, Ralph Casale, Reinier Beeuwkes, Steven A. Kates
Принадлежит: Ischemix LLC

The present invention relates, in various embodiments, to a compound represented by Structural Formula (I), pharmaceutically acceptable salts or prodrugs thereof, and compositions comprising said compounds, or pharmaceutically acceptable salts or prodrugs thereof. Methods of using compounds of Structural Formulas (I) and (la) or compositions comprising compounds of Structural Formulas (I) and (la), or pharmaceutically acceptable salts or prodrugs thereof, to treat ischemia or ischemia-reperfusion injury are also disclosed.

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Номер записи: 10
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: 11
12-12-2013 дата публикации

SMALL MOLECULE INHIBITORS OF AGBL2

Номер: US20130331328A1
Автор: Byers Stephen W., Dakshanamurthy Sivanesan, Sahab Ziad
Принадлежит: GEORGETOWN UNIVERSITY

Small molecule inhibitors of AGBL2 are provided, as well as methods of using the inhibitors to treat or prevent cancer and neurologic disorders. 2. The compound of claim 1 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.6. The compound of claim 5 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.1110. A composition comprising a compound of any of - and a pharmaceutically acceptable carrier.13. The method of claim 12 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.17. The method of claim 16 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.2322. The method of any of - claims 1 , further comprising administering a second therapeutic agent to the subject.24. The method of claim 23 , wherein the second therapeutic agent is a chemotherapeutic agent.26. The method of claim 25 , wherein Rand Rcombine to form a substituted or unsubstituted heterocycloalkyl.30. The method of claim 29 , wherein Rand Rcombine to form a substituted or unsubstituted cycloalkyl.3635. The method of any of - claims 25 , further comprising administering a second therapeutic agent to the subject.37. The method of claim 36 , wherein the second therapeutic agent is an anti-depressant or an anxiolytic. This application claims priority to U.S. Provisional Application No. 61/443,069, filed Feb. 15, 2011, which is incorporated herein by reference in its entirety.The removal of the C-terminal tyrosine of α-tubulin to form detyrosinated α-tubulin is involved in several aspects of microtubule function, including kinesin interactions, spindle dynamics, mitosis, and neuronal specification. Microtubules containing large amounts of detyrosinated α-tubulin are more stable and resistant to depolymerization by destabilizing agents. Further, detyrosinated α-tubulin has been shown to be elevated in aggressive breast and prostate cancers.Provided herein are small molecule inhibitors of ATP/GTP binding protein ...

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Номер записи: 12
26-12-2013 дата публикации

Angiotensin converting enzyme inhibitory peptide

Номер: US20130345396A1
Автор: Hitomi Aota, Katsutoshi Sugimoto, Riichiro Uchida, Takeharu Nakahara, Takuya Sato
Принадлежит: Kikkoman Corp

To provide ACE inhibitory peptides which can effectively inhibit ACE by a small amount of ingestion and have no fear of causing side effects and which can be orally ingested easily during daily life by persons having high blood pressure, and compositions comprising the peptides. The peptides represented by the following structural formulae (1) to (9), and salts thereof are provided. (1) Asp-Arg-Pro, (2) Asn-Trp, (3) Val-Gly-Leu, (4) Ile-Gly-Val, (5) Gly-Val-Pro, (6) Ile-Pro-Tyr, (7) pyroGlu-Pro, (8) Tyr-Thr, (9) Pro-Trp

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Номер записи: 13
30-01-2014 дата публикации

Compounds for enzyme inhibition

Номер: US20140031297A1
Автор: Congcong M. Sun, Guy J. Laidig, Han-Jie Zhou, Kevin D. Shenk
Принадлежит: Onyx Therapeutics Inc

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. 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. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles.

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Номер записи: 14
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: 15
20-02-2014 дата публикации

Compounds for enzyme inhibition

Номер: US20140050737A1
Автор: Congcong M. Sun, Guy J. Laidig, Han-Jie Zhou, Kevin D. Shenk
Принадлежит: Onyx Therapeutics Inc

Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. 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. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles.

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Номер записи: 16
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: 17
06-03-2014 дата публикации

Binding ligand linked drug delivery conjugates of tubulysins

Номер: US20140066594A1
Автор: Christopher P. Leamon, Iontcho R. Vlahov, Kevin Yu Wang
Принадлежит: Endocyte Inc

Described herein are compounds, pharmaceutical compositions and methods for treating pathogenic cell populations. The compounds described herein include conjugates of tubulysins and vitamin receptor binding ligands. The conjugates also include a releasable bivalent linker.

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Номер записи: 18
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: 19
07-01-2021 дата публикации

Flavor compositions and screening methods for identifying the same

Номер: US20210000152A1
Автор: Mathias SALGER, Thomas Hofmann, Timo Stark
Принадлежит: Mars Inc

The presently disclosed subject matter relates to peptides and flavor compositions that include at least one, two, three, four, five or more peptide compounds, and screening methods for identifying the same. The flavor compositions can be used to enhance or modify the taste and/or flavor of various edible compositions such as human food products and pet food products.

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Номер записи: 20
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: 21
14-01-2016 дата публикации

PEPTIDE MOLECULAR MATERIALS

Номер: US20160009763A1
Автор: HSU Shu-Min, LIN Hsin-Chieh
Принадлежит: NATIONAL CHIAO TUNG UNIVERSITY

This invention provides a novel peptide molecular material, wherein the molecular structure of the material is a combination of halogen-substituted or unsubstituted aryl and a peptide molecular. This material can self-assemble to form a nanofiber and form a hydrogel. The hydrogel has various properties, including low cytotoxicity, the promotion of cell growth and migration as well as being stable under a physiological condition and a human body temperature. 2. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare hydrogen atoms; Rand Rare independently selected from a hydrogen atom and C-Caralkyl; x is 1; and y is 1.3. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare independently selected from a hydrogen atom; Rand Rare independently selected from the group consisting of a hydrogen atom claim 1 , C-Calkyl claim 1 , C-Caralkyl and C-Chydroxyaralkyl; x is 1; and y is 2.4. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare independently selected from a hydrogen atom; Rand Rare independently selected from the group consisting of a hydrogen atom and C-Caralkyl; x is 1; and y is 3.5. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare hydrogen atoms; Rand Rare independently selected from the group consisting of a hydrogen atom claim 1 , C-Calkyl and C-Caminoalkyl; x is 1; and y is 5.6. The peptide molecular material according to claim 1 , wherein A is phenyl; Rand Rare hydrogen atoms; Rand Rare independently selected from a hydrogen atom claim 1 , C-Calkyl and C-Caminoalkyl; x is 0 to 2; and y is 5.7. The peptide molecular material according to claim 1 , wherein A is phenyl substituted by fluorine; Rand Rare hydrogen atoms; Rand Rare independently selected from the group consisting of a hydrogen atom claim 1 , C-Calkyl claim 1 , C-Caralkyl and C ...

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Номер записи: 22
08-01-2015 дата публикации

Selective caspase inhibitors and uses thereof

Номер: US20150011458A1
Автор: Jan-Eric Ahlfors, Khalid Mekouar
Принадлежит: NOVAGENESIS FOUNDATION

The present invention relates to compounds of Formula I, IA, II, HA, III, or IHA and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more caspases. Also described are methods where the compounds of Formula I, IA, II, IIA, III, or IIIA are used in the prevention and/or treatment of various diseases and conditions in subjects, including caspase-mediated diseases such as sepsis, myocardial infarction, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative disease (e.g. multiple sclerosis (MS) and Alzheimer's, Parkinson's, and Huntington's diseases).

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Номер записи: 23
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: 24
09-01-2020 дата публикации

COMPOUNDS

Номер: US20200010504A1
Автор: Baker William R., Kawas Leen H., Singh Jasbir, Stewart Lansing Joseph
Принадлежит:

The present technology relates to compounds, kits, compositions, and methods useful for the treatment of numerous pathologies including dementia, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases, spinal cord injury, traumatic brain injury, diabetes and metabolic syndrome, defective wound healing, and/or sensorineural hearing and vision loss. 56-. (canceled)7. The compound of claim 1 , where Ris a C-Calkyl claim 1 , Rand Rare both hydrogen and Ris hydrogen.8. The compound of claim 2 , where m is 0 claim 2 , Ris a C-Calkyl claim 2 , and Rand Rtogether form a spirocyclic ring system.9. The compound of claim 2 , where m is 1 or 2 claim 2 , Ris a C-Calkyl claim 2 , Rand Rtogether form a spirocyclic ring system claim 2 , and Ris selected from the group consisting of: hydrogen claim 2 , deuterium claim 2 , F claim 2 , F claim 2 , and F.10. The compound of claim 3 , where Ris a C-Calkyl claim 3 , Ris —C(═O)—Y claim 3 , and Rand Rare both hydrogen.11. The compound of claim 3 , where Ris a C-Calkyl claim 3 , Ris —C(═O)—CH(NH)Pr claim 3 , Rand Rare both hydrogen.12. The compound of claim 3 , where Ris a C-Calkyl claim 3 , Ris —C(═O)—CH(NH)Pr claim 3 , Rand Rare both hydrogen claim 3 , m is 1 or 2 and Ris F.13. The compound of claim 3 , where Ris a C-Calkyl claim 3 , Ris PO(OH) claim 3 , and Rand Rare both hydrogen.1419-. (canceled)2123-. (canceled)24. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier or excipient.2526-. (canceled)27. A method for treating a disease state or condition comprising administering of an effective amount of a pharmaceutical composition according to to a subject in need thereof.28. The method of claim 27 , wherein the disease is neurodegenerative disease.29. The method of claim 28 , wherein the disease is selected from the group consisting of: Alzheimer's disease claim 28 , Parkinson's disease claim 28 , amyotrophic lateral sclerosis ...

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Номер записи: 25
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: 26
25-01-2018 дата публикации

Ibat inhibitors for the treatment of liver diseases

Номер: US20180022776A1
Автор: Hans Graffner, Ingemar Starke, Per-Goran Gillberg
Принадлежит: ALBIREO AB

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.

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Номер записи: 27
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: 28
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: 29
28-01-2021 дата публикации

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE

Номер: US20210024575A1
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. 118-. (canceled)19. A method for treating a cancer characterized by the presence of an IDH1 mutation in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of mutant IDH1.20. The method of wherein the cancer is myelodysplastic syndrome (MDS).21. The method of wherein the IDH1 mutation is an IDH1 R132X mutation.23. The method of wherein the IDH1 mutation is an R132H or R132C mutation.24. A method of reducing the level of 2-hydroxyglutarate (2HG) in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of mutant IDH1.25. The method of claim 24 , wherein the subject has been diagnosed with a cancer characterized by the presence of an IDH1 mutation.26. The method of wherein the IDH1 mutation is an IDH1 R132X mutation.27. The method of wherein the IDH1 mutation is and R132H or R132C mutation.29. The method of wherein the IDH1 mutation is an IDH1 R132X mutation.30. The method of wherein the IDH1 mutation is an R132H or R132C mutation. This application is a continuation of U.S. Ser. No. 16/427,691, filed May 31, 2019, which is a continuation of U.S. Ser. No. 15/809,325, filed Nov. 10, 2017, which is a continuation of U.S. Ser. No. 15/279,146, filed Sep. 28, 2016, which is a continuation of U.S. Ser. No. 13/745,005, filed Jan. 18, 2013, which claims priority under 35 U.S.C. § 119 from International Application No. PCT/CN2012/070601, filed Jan. 19, 2012, each of which is incorporated herein by reference in its entirety.Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate (i.e., α-ketoglutarate). These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). ...

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Номер записи: 30
04-02-2016 дата публикации

BENZIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING BENZIDINE DERIVATIVE FOR TREATING LIVER DISEASE CAUSED BY HEPATITIS C VIRUS

Номер: US20160031810A1
Автор: Bae Il Hak, Choi Jin Kyu, JANG Sung Key, Keum Sun Ju, Kim Byeong Moon, KIM HEE SUN, LEE Seung Gi
Принадлежит:

The disclosed compounds have antiviral activity against C-type virus, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient for preventing or treating liver disease caused by hepatitis C virus. The benzidine derivative according to the present invention has excellent antiviral activity against hepatitis C virus and exhibits excellent medicinal activity in the living body, and thus the pharmaceutical composition containing the same as an active ingredient can be useful as a pharmaceutical composition for preventing or treating liver disease, such as acute hepatitis C, chronic hepatitis C, cirrhosis, or hepatocellular carcinoma, caused by C-type virus. 2. The compound represented by formula 1 claim 1 , the optical isomer thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein:{'sup': 1', '2', '12', '13', '14, 'sub': 1-5', '1-5', '6-8, 'Rand Rare independently —H, —OH, halogen, Cstraight or branched alkyl, Cstraight or branched alkoxy, unsubstituted or substituted Caryl, —NRR, or —NHC(═O)R,'}{'sub': 6-8', '1-5', '1-5, 'in the said substituted Caryl, one or more substituents selected from the group consisting of Cstraight or branched alkyl, Cstraight or branched alkoxy, and halogen can be substituted;'}{'sup': 12', '13, 'sub': '1-3', 'Rand Rare —H, or Cstraight or branched alkyl;'}{'sup': '14', 'sub': '1-3', 'Ris —H, or Cstraight or branched alkoxy;'}{'sup': 1', '2, 'sub': '5-8', 'Rand Rcan form Cheterocycloalkyl containing one or more hetero atoms selected from the group consisting of N, O and S along with carbon atoms which are conjugated to the same;'}{'sup': 3', '4', '5', '6', '7', '8', '9', '10, 'sub': '1-5', 'R, R, R, R, R, R, R, and Rare independently —H, halogen, or unsubstituted or substituted Cstraight or branched alkyl in which one or more halogens are substituted,'}{'sup': 4', '7', '6', '9, ' ...

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Номер записи: 31
04-02-2016 дата публикации

Dipeptide and tripeptide epoxy ketone protease inhibitors

Номер: US20160031934A1
Автор: David C. Moebius, Dustin McMinn, Henry Johnson
Принадлежит: Onyx Therapeutics Inc

Provided herein are dipeptide and tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X): and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of proliferative diseases including cancer and autoimmune diseases.

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Номер записи: 32
01-02-2018 дата публикации

Ibat inhibitors for the treatment of liver diseases

Номер: US20180030088A1
Автор: Hans Graffner, Ingemar Starke, Per-Goran Gillberg
Принадлежит: ALBIREO AB

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.

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Номер записи: 33
01-02-2018 дата публикации

IBAT INHIBITORS FOR THE TREATMENT OF LIVER DISEASES

Номер: US20180030089A1
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)2. A method for treating cholestasis in a subject , the method comprising orally administering to a subject in need of such treatment a therapeutically effective amount an IBAT inhibitor , wherein the IBAT inhibitor is 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 , or a pharmaceutically acceptable salt thereof.3. The method of claim 2 , wherein treatment of cholestasis comprises treatment of pruitus.4. The method of claim 2 , wherein treatment of cholestasis comprises decreasing the level of serum bile acids in the subject.5. The method of claim 2 , wherein treatment of cholestasis comprises decreasing the level of liver bile acids in the subject.6. The method of claim 2 , wherein the treatment of cholestasis comprises treatment of one or more of Alagilles syndrome (ALGS) claim 2 , progressive familial intrahepatic cholestasis (PFIC) claim 2 , autoimmune hepatitis claim 2 , primary biliary cirrhosis (PBC) claim 2 , liver fibrosis claim 2 , non alcoholic fatty liver disease claim 2 , non-alcoholic steatohepatitis (NASH) claim 2 , portal hypertension claim 2 , primary sclerosing cholangitis (PSC) claim 2 , cystic fibrosis claim 2 , and malignancy causing obstruction of the biliary tree.7. The method of claim 2 , wherein the cholestasis impacts at least the extrahepatic or intrahepatic biliary tree of the subject.8. The method of claim 2 , wherein the cholestasis impacts at least the extrahepatic biliary tree of the subject.9. The method of claim 2 , wherein the treatment of cholestasis comprises treatment of drug-induced hepatitis or cholestasis of ...

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Номер записи: 34
11-02-2016 дата публикации

CYTOTOXIC AND ANTI-MITOTIC COMPOUNDS, AND METHODS OF USING THE SAME

Номер: US20160038606A1
Автор: BABCOOK John, Bourque Elyse Marie Josee, HEDBERG Bradley John, HSIEH Tom Han Hsiao, MANDEL Alexander Laurence, RICH James R., Winters Geoffrey C.
Принадлежит:

Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity. 4. The compound according to or , wherein each optionally substituted alkyl , optionally substituted alkylamino , optionally substituted cycloalkyl , optionally substituted aryl , optionally substituted heterocyclyl and optionally substituted heteroaryl is , independently , optionally substituted with ═O , ═S , —OH , —OR , —OCR , —SH , —SR , —SOCR , —NH , —N , —NHR , —N(R) , —NHCOR , —NRCOR , —I , —Br , —Cl , —F , —CN , —COH , —COR , —CHO , —COR , —CONH , —CONHR , —CON(R) , —COSH , —COSR , —NO , —SOH , —SORor —SORwherein each Ris , independently , alkyl optionally substituted with halogen , —OH or —SH.5. The compound according to or , wherein each optionally substituted aryl and optionally substituted heteroaryl is , independently , selected from the group consisting of optionally substituted phenyl , optionally substituted naphthyl , optionally substituted anthracyl , optionally substituted phenanthryl , optionally substituted furyl , optionally substituted pyrrolyl , optionally substituted thiophenyl , optionally substituted benzofuryl , optionally substituted benzothiophenyl , optionally substituted quinolinyl , optionally substituted isoquinolinyl , optionally substituted imidazolyl , optionally substituted thiazolyl , optionally substituted oxazolyl , and optionally substituted pyridinyl.128. The composition according to any one of - wherein R claims 2 , R claims 2 , and R claims 2 , are each methyl.138. The composition according to any one of - claims 2 , wherein Ris H claims 2 , Ris methyl claims 2 , and Ris methyl.1413. A pharmaceutical composition ...

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Номер записи: 35
08-02-2018 дата публикации

Nmda antagonist prodrugs

Номер: US20180037550A1
Автор: Annika Kers, Dirk Reinhold Weigelt, Gunnar Nordvall, Katharina Högdin, Michael Balestra, Michael Quirk, Per Jonas Malmborg, Peter Robert Bernstein
Принадлежит: AstraZeneca AB

Prodrugs of an NMDA antagonist, (S)-1-phenyl-2-(pyridin-2-yl)ethanamine, useful for the treatment of depression (particularly major depressive disorder) or pain; compositions comprising them, and methods of making them.

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Номер записи: 36
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: 37
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: 38
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: 39
15-02-2018 дата публикации

1,2,4-OXADIAZOLE AND THIADIAZOLE COMPOUNDS AS IMMUNOMODULATORS

Номер: US20180044303A1
Автор: Naremaddepalli Seetharamaiah Sudarshan, RAMACHANDRA MURALIDHARA, Sasikumar Pottayil Govindan N.
Принадлежит:

The present invention relates to 1,2,4-oxadiazole compounds of formula (I) and their use to inhibit the programmed cell death 1 (PD-1) signaling pathway and/or for treatment of disorders by inhibiting an immunosuppressive signal induced by PD-1, PD-L1 or PD-L2. 3. The compound of or , wherein Ris H.4. The compound of any one of to , wherein Ris —CO-[Aaa1] , wherein Aaa1 and ‘m’ are as defined in .5. The compound of any one of to , wherein the side chain of Aaa1 comprises a (C-C)alkyl group optionally substituted by one or more substituents selected from amino , alkylamino , acylamino , carboxylic acid , carboxylate , thiocarboxylate , thioacid , —CONRR , hydroxy , cycloalkyl , (cycloalkyl)alkyl , aryl , heterocyclyl , heteroaryl , guanidino , —SH , —S(alkyl); optionally wherein cycloalkyl , aryl , heterocyclyl and heteroaryl are further substituted by one or more substituents such as hydroxy , alkoxy , halo , amino , nitro , cyano or alkyl.6. The compound of any one of to , wherein the side chain of Aaa1 comprises a (C-C)alkyl group substituted by one or more substituents selected from amino , acylamino , carboxylic acid , —CONRR , hydroxy , cycloalkyl , aryl , heteroaryl , guanidino , —SH and —S(alkyl); wherein Rand Rindependently are hydrogen , alkyl , aryl or heterocyclyl.7. The compound of any one of to , wherein Ris —CORwherein Ris as defined in .8. The compound of any one of to , wherein Ris —SOR , wherein Ris as defined in .9. The compound of any one of to , wherein Ris H.10. The compound of any one of to , wherein Ris (C-C)alkyl optionally substituted by one or more substituents selected from amino , alkylamino , acylamino , carboxylic acid , carboxylate , carboxylic acid ester , thiocarboxylate , thioacid , —CONRR , hydroxy , cycloalkyl , (cycloalkyl)alkyl , aryl , arylalkyl , heterocyclyl , (heterocyclyl)alkyl , heteroaryl , (heteroaryl)alkyl , guanidino , —SH , —S(alkyl); optionally wherein cycloalkyl , aryl , heterocyclyl and heteroaryl are further ...

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Номер записи: 40
25-02-2021 дата публикации

Antimicrobial compounds and/or modulators of microbial infections and methods of using the same

Номер: US20210054025A1
Автор: Jack Geno Samaritoni, Martin James O'Donnell, William Leonard Scott
Принадлежит: Indiana University Research And Technology Corp

Some embodiments include compounds that can inhibit the growth of bacterial and/or inhibit or reduce microbial infections caused by one or more microorganisms (e.g., Pseudomonas aeruginosa and Cryptococcus neoformans) and methods of using these compounds to treat microbial infection and outbreaks and/or to reduce the formation of biofilms. Other embodiments include synthesis of the compounds that can inhibit the growth of one or more microorganisms and/or inhibit or reduce microbial infections.

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Номер записи: 41
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: 42
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: 43
05-03-2015 дата публикации

Lipoyl compounds and methods for treating ischemic injury

Номер: US20150065564A1
Автор: Alan S. Lader, Alexander B. Baguisi, Ralph Casale, Reinier Beeuwkes, Steven A. Kates
Принадлежит: Ischemix LLC

The present invention relates, in various embodiments, to a compound represented by Structural Formula (I), pharmaceutically acceptable salts or prodrugs thereof, and compositions comprising said compounds, or pharmaceutically acceptable salts or prodrugs thereof. Methods of using compounds of Structural Formulas (I) and (Ia) or compositions comprising compounds of Structural Formulas (I) and (Ia), or pharmaceutically acceptable salts or prodrugs thereof, to treat ischemia or ischemia-reperfusion injury are also disclosed.

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Номер записи: 44
28-02-2019 дата публикации

Polyconjugates for Delivery of RNAi triggers to Tumor Cells In Vivo

Номер: US20190062748A1
Автор: Almeida Aaron M., Blokhin Andrei V., Carlson Jeffrey C., Cheng Weijun, Rozema David B., Wong So
Принадлежит:

The present invention is directed compositions for delivery of RNA interference (RNAi) triggers to integrin positive tumor cells in vivo. The compositions comprise RGD ligand-targeted amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or conjugate) are further covalently linked to an RNAi trigger. 5. The RGD ligand of claim 4 , wherein Ris the side group of alanine.6. The RGD ligand of claim 4 , wherein Ris the side group of phenylalanine.7. The RGD ligand of claim 4 , wherein Ris the side group of leucine.8. The RGD ligand of claim 4 , wherein Ris the side group of isoleucine.9. The RGD ligand of claim 4 , wherein Ris the side group of tryptophan.10. The RGD ligand of claim 4 , wherein Ris the side group of citrulline.11. The RGD ligand of claim 4 , wherein Ris the side group of glycine.12. The RGD ligand of claim 4 , wherein Ris the side group of threonine.13. The RGD ligand of claim 4 , wherein Ris the side group of asparagine.14. The RGD ligand of claim 4 , wherein Ris the side group of glutamine.16. The masking agent of claim 15 , wherein Ris citrulline.19. The masking agent of claim 18 , wherein n is 3. The present application is a continuation of U.S. patent application Ser. No. 15/278,518, filed Sep. 28, 2016, which is a continuation of Ser. No. 14/452,626, filed Aug. 6, 2014, now U.S. Pat. No. 9,487,556, which claims the benefit of U.S. Provisional Patent Application No. 61/863,056, filed Aug. 7, 2013, the contents of each of which are incorporated herein in their entirety.The delivery of RNAi triggers and other substantially cell membrane impermeable compounds into a living cell is highly restricted by the complex membrane system of the cell. Drugs used in antisense, RNAi, and gene therapies are relatively large ...

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Номер записи: 45
09-03-2017 дата публикации

Use of substances for the treatment of loss of eyesight in humans with glaucoma and other degenerative eye diseases

Номер: US20170065664A1
Автор: Hermann Russ
Принадлежит: Ramot at Tel Aviv University Ltd

Methods for the prevention and treatment of ocular disorders, in particular glaucoma, through blocking the toxic effects of β-amyloid (Aβ) derivatives, and pharmaceutical compositions for effecting such prevention and treatment thereof.

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Номер записи: 46
15-03-2018 дата публикации

Cholecystokinin 2 receptor targeted nir imaging and use thereof

Номер: US20180071408A1
Автор: Mohammad Noshi, Pravin Gagare, Sumith A. Kularatne
Принадлежит: On Target Laboratories LLC

Compounds are described herein where CCK2R targeting ligands are attached to an imaging agent through a linker. The compounds can be used in the detection, diagnosis, imaging and treatment of cancer.

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Номер записи: 47
05-03-2020 дата публикации

PEPTIDOMIMETICS FOR THE TREATMENT OF NOROVIRUS INFECTION

Номер: US20200071354A1
Автор: Amblard Franck, KEUSCH Bradley J., KOVARI Ladislau, KUIPER Benjamin D., Liu Peng, SCHINAZI RAYMOND F., Zhou Shaoman
Принадлежит: EMORY UNIVERSITY

The present invention is directed to compounds, compositions and methods for preventing, treating or curing Norovirus infection in human subjects or other animal hosts. 10. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically-acceptable carrier.11. The composition of claim 10 , wherein the composition is a transdermal composition or a nanoparticulate composition.12. The pharmaceutical composition of claim 11 , further comprising a second antiviral agent.13. The pharmaceutical composition of claim 12 , wherein the second antiviral agent is selected from the group consisting of a polymerase inhibitors claim 12 , protease inhibitors claim 12 , anti-emetics claim 12 , anti-dianrheals claim 12 , cellular deubiquitinase inhibitors claim 12 , IFN-x inhibitors claim 12 , agents of distinct or unknown mechanism claim 12 , and combinations thereof.14. (canceled)15. A method for treating a host infected with Norovirus claim 12 ,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'preventing an Norovirus infection, curing an Norovirus infection, or reducing the biological activity of an infection with Norovirus in a host, comprising administering an effective amount of a compound of to a patient in need of treatment thereof.'}16. The method of claim 12 , wherein the method further comprising administering another Norovirus virus agent in combination or alternation with the compound of .17. A method for treating claim 1 , preventing claim 1 , or curing infections caused by Sapporo virus claim 1 , Gastroenteritis claim 1 , Jena virus claim 1 , Murine norovirus claim 1 , Fulminant organ dysfunction claim 1 , Pistoia virus claim 1 , Hemorrhagic enteritis claim 1 , Canine norovirus claim 1 , Swine43 claim 1 , Porcine enteric calicivirus claim 1 , Mink enteric calicivirus claim 1 , Rabbit hemorrhagic disease virus claim 1 , European brown hare syndrome virus claim 1 , Bovine enteric calicivirus/Newbury-1 virus) claim 1 , Bovine enteric calicivirus/ ...

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Номер записи: 48
05-06-2014 дата публикации

Anti-viral compounds

Номер: US20140155382A1
Автор: Allan C. Krueger, Charles W. Hutchins, David A. Degoey, Warren M. Kati, William A. Carroll
Принадлежит: AbbVie Inc

Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

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Номер записи: 49
19-03-2020 дата публикации

EPOXYKETONE COMPOUNDS FOR ENZYME INHIBITION

Номер: US20200087343A1
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. 118-. (canceled)22. The method of claim 19 , wherein Rin the compound of Formula (I) is Calkyl claim 19 , Calkoxyalkyl claim 19 , aryl claim 19 , heteroaryl claim 19 , Caralkyl or Cheteroaralkyl.23. The method of claim 22 , wherein Rin the compound of Formula (II) is methyl-oxy-methyl claim 22 , 4-pyridylmethyl claim 22 , isobutyl claim 22 , benzyl or 4-thiazolyl-methyl.24. The method of claim 19 , wherein Rin the compound of Formula (I) is Calkyl claim 19 , aryl claim 19 , heteroaryl claim 19 , Caralkyl or Cheteroaralkyl.25. The method of claim 24 , wherein Ris isobutyl claim 24 , 4-pyridylmethyl or benzyl.27. The method of claim 19 , wherein the compound of Formula (I) is administered as a pharmaceutical composition comprising a compound of Formula (I) claim 19 , and a pharmaceutically acceptable carrier.28. The method of claim 19 , wherein the compound of Formula (I) is administered through a parenteral route.29. The method of claim 28 , wherein the compound is administered subcutaneously claim 28 , intravenously claim 28 , intramuscularly claim 28 , intraarterially claim 28 , intrathecally claim 28 , intracapsularly claim 28 , intraorbitally claim 28 , intra cardiacally claim 28 , intradermally claim 28 , intraperitoneally claim 28 , transtracheally claim 28 , subcuticularly claim 28 , intraarticularly claim 28 , subcapsularly claim 28 , subarachnoidly claim 28 , intraspinally claim 28 , intrasternally claim 28 , or through infusion.30. The method of claim 19 , wherein the compound is administered through a non-parenteral route.31. The method of claim 30 , wherein the compound is administered orally claim 30 , enterally claim 30 , ...

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Номер записи: 50
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: 51
28-03-2019 дата публикации

NEUROPEPTIDE S RECEPTOR (NPSR) AGONISTS

Номер: US20190092809A1
Автор: Hassler Carla, NARAYANAN Sanju, Runyon Scott, Shiner Craig
Принадлежит:

Neuropeptide S receptor agonists are provided. The NPS agonists include peptidomimetic analogs exhibiting affinity for and activity at the neuropeptide S receptor. The molecules may be useful in the treatment of disorders, syndromes and conditions mediated by modulation of the neuropeptide S receptor such as substance abuse, narcolepsy, insomnia, obesity, cognitive decline, dementia, Alzheimer's disease, panic disorder, generalized anxiety, PTSD, phobias, schizophrenia and as supportive medication during any kind of cessation program in cognitive behavioral therapy, such as drug addiction, eating disorders and gambling. 3. The compound of claim 2 , wherein:{'sup': '1', 'Ris phenyl, benzyl, benzyloxy, or phenethyl;'}{'sup': '2', 'Ris benzyl;'}{'sup': '4', 'sub': '2', 'Ris a six membered saturated ring substituted with one C(O)NHgroup, and'}{'sup': 3', '5, 'Rand Rare each H.'}4. The compound of claim 2 , wherein Ris phenyl or benzyl claim 2 , and Ris benzyl.5. The compound of claim 2 , wherein Ris benzamido claim 2 , Ris benzyl claim 2 , Ris C-Camidoalkyl claim 2 , and Ris H or benzyl.6. The compound of claim 5 , wherein Ris —CH(CH)CHC(O)NHor —CH(Ph)-CH—C(O)NH.7. The compound of claim 2 , wherein Ris benzamido claim 2 , Ris benzyl claim 2 , Ris a six membered saturated ring substituted with one C(O)NH claim 2 , and Ris methyl.8. The compound of claim 2 , wherein Ris H or phenethyl claim 2 , Ris C-Carylalkenyl claim 2 , and Ris a six membered saturated ring substituted with one C(O)NH.9. The compound of claim 2 , wherein Ris C-C-alkylcycloalkyl claim 2 , or branched or unbranched C-C-alkyl claim 2 , Ris benzyl claim 2 , Ris a six membered saturated ring substituted with one C(O)NH claim 2 , and Rand Rare H.10. The compound of claim 9 , wherein Ris CHCH-cyclohexyl or isopentyl.11. The compound of claim 2 , wherein Ris phenethyl claim 2 , Ris benzyl claim 2 , Ris H or lysine side chain claim 2 , and Ris a five membered saturated ring substituted with one C(O)NHgroup ...

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Номер записи: 52
19-04-2018 дата публикации

CHEMICALLY AND METABOLICALLY STABLE DIPEPTIDE POSSESSING POTENT SODIUM CHANNEL BLOCKER ACTIVITY

Номер: US20180104241A1
Автор: Johnson Michael
Принадлежит: PARION SCIENCES, INC.

A very stable, selective and nrenally safe sodium channel blocker represented by the formula: 2. The method of claim 1 , wherein the treating is conducted in CHCl.3. The method of claim 1 , wherein the aqueous HCl is 1 N aqueous HCl.4. The method of claim 1 , further comprising claim 1 , subsequent to the treating and prior to the azeotroping claim 1 , concentrating the resulting reaction mixture under vacuum. This application is a Continuation of U.S. application Ser. No. 15/485,361 filed Apr. 12, 2017, pending, which is a Continuation of U.S. application Ser. No. 14/129,734, filed on Jan. 3, 2014, now U.S. Pat. No. 9,072,738, which is a National Stage of International No. PCT/US12/44372, filed on Jun. 27, 2012, which claims priority to Provisional Application Ser. No. 61/501,524, filed on Jun. 27, 2011.The present invention relates to epithelial sodium channel blocker 3,5-diamino-6-chloro-N-(N-(4-(4-((S)-3-(dimethylamino)-4-((S)-1-(dimethylamino)-6-guanidino-1-oxohexan-2-ylamino)-4-oxobutyl)phenyl)butyl)carbamimidoyl)pyrazine-2-carboxamide (I). The present invention also includes a variety of methods of treatment using this inventive sodium channel blocker. The present invention also relates to novel compounds for the treatment of dry eye, particularly including 3,5-diamino-6-chloro-N-(N-(4-(4-((S)-3-(dimethylamino)-4-((S)-1-(dimethylamino)-6-guanidino-1- oxohexan-2-ylamino)-4-oxobutyl)phenyl)butyl)carbamimidoyl)pyrazine-2-carboxamide (I) and its pharmaceutically acceptable salt forms, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.The mucosal surfaces at the interface between the environment and the body have evolved a number of “innate defense”, i.e., protective mechanisms. A principal form of such innate defense is to cleanse these surfaces with liquid. Typically, the quantity of the liquid layer on a mucosal surface reflects the balance between epithelial ...

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Номер записи: 53
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: 54
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: 55
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: 56
30-04-2015 дата публикации

AGRICULTURAL PLANT-PROTECTING AGENTS CONTAINING DIPEPTIDE DERIVATIVE AS ACTIVE INGREDIENT

Номер: US20150119251A1
Автор: Hong In Seok, LEE Se Won, Moon Surk Sik, Park Jin Woo, Park Kyung Seok
Принадлежит:

Provided is an agricultural plant-protecting agent including a dipeptide derivative or an agro-pharmaceutically acceptable salt thereof as an active ingredient, which has a plant disease-preventing effect, a plant growth-promoting effect, and a plant immunity-activating effect. 2. The agricultural plant-protecting agent claim 1 , according to claim 1 , wherein the dipeptide derivatives are represented by the above-described chemical formula 1 is a racemic mixture or isomeric compound.3. The agricultural plant-protecting agent according to claim 1 , wherein the R claim 1 , R claim 1 , and Rare the same or different from each other claim 1 , and represent a hydrogen atom claim 1 , an acetyl group claim 1 , a hexanoyl group claim 1 , a hexadecanoyl group claim 1 , an octadecanoyl group claim 1 , a benzoyl group claim 1 , a 4-hexylbenzoyl group claim 1 , a 2-phenylacetyl group claim 1 , a 3-phenylpropanonyl group claim 1 , a methoxycarbonyl group claim 1 , an ethoxycarbonyl group claim 1 , a t-butoxycarbonyl group claim 1 , a hexadecanoxy carbonyl group claim 1 , an octadecanoxycarbonyl group claim 1 , a phenoxycarbonyl group claim 1 , and a 4-hexylbenzyloxycarbonyl group; the R claim 1 , R claim 1 , R claim 1 , and Rare the same or different from each other claim 1 , and represent a hydrogen atom claim 1 , a methyl group claim 1 , an ethyl group claim 1 , a n-propyl group claim 1 , an isopropyl group claim 1 , a 1-methylpropyl group claim 1 , a 2-methylpropyl group claim 1 , a hydroxymethyl group claim 1 , a 1-hydroxyethyl group claim 1 , a 2-hydroxyethyl group claim 1 , an imidazole-4-yl-methyl group claim 1 , a 2-methylthioethyl group claim 1 , a benzyl group claim 1 , a 4-hydroxybenzyl group claim 1 , a phenethyl group claim 1 , a mercaptomethyl group claim 1 , a methylthiomethyl group claim 1 , a methylthioethyl group claim 1 , a tritylthiomethyl group claim 1 , a tritylthioethyl group claim 1 , a methoxycarbonylmethyl group claim 1 , an ethoxycarbonylmethyl group ...

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Номер записи: 57
27-04-2017 дата публикации

Selective caspase inhibitors and uses thereof

Номер: US20170114092A1
Автор: Jan-Eric Ahlfors, Khalid Mekouar
Принадлежит: Genesis Technologies Ltd

The present invention relates to compounds of Formula I, IA, II, IIA, III, or IIIA and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more caspases. Also described are methods where the compounds of Formula I, IA, II, IIA, III, or IIIA are used in the prevention and/or treatment of various diseases and conditions in subjects, including caspase-mediated diseases such as sepsis, myocardial infarction, ischemic stroke, spinal cord injury (SCI), traumatic brain injury (TBI) and neurodegenerative disease (e.g. multiple sclerosis (MS) and Alzheimer's, Parkinson's, and Huntington's diseases).

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Номер записи: 58
12-05-2016 дата публикации

THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE

Номер: US20160130298A1
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)—C-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 or claim 1 , wherein each Rand Ris independently aryl optionally substituted with one to three Rgroups.5. The compound of any one 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 ...

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Номер записи: 59
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: 60
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: 61
02-05-2019 дата публикации

Dipeptide analogs as tgf-beta inhibitors

Номер: US20190127420A1
Автор: Bini Mathew, Joanne MURPHY-ULLRICH, Mark J. Suto, Vandana Gupta
Принадлежит: Southern Research Institute, UAB RESEARCH FOUNDATION

The present disclosure is concerned with dipeptide analogs that are capable of inhibiting TGF-β and methods of treating cancers such as, for example, multiple myeloma and a hematologic malignancy, methods for immunotherapy, and methods of treating fibrotic conditions using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

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Номер записи: 62
03-06-2021 дата публикации

CONJUGATES AND METHODS OF USING THE SAME

Номер: US20210162057A1
Автор: Berry David Arthur, BOGART Elijah Lane, Casey, DOUD Devin Forest Reed, IM Joo Hyun, ISAAC Dervla Tamara, JR. John Patrick, LIU Jenny, MASSARI Ferdinand Edward, MYERS Robert Walter, PECK Spencer Cory, PROUDFOOT John Robert, ROSS Cheri, TAYLOR Steven John
Принадлежит:

Disclosed are conjugates including a recognition element covalently bonded to or linked through a linker to a payload. The payload is a pharmaceutical agent (e.g., an antineoplastic agent, anti-infective agent, or anti-inflammatory agent) or a diagnostic agent. Also disclosed are methods of using the conjugates. 1. A conjugate , or a pharmaceutically acceptable salt thereof , comprising a recognition element covalently bonded to or linked through a linker to a payload , wherein the payload is a pharmaceutical agent.2. The conjugate of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein the payload is an antineoplastic agent.3. The conjugate of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein the antineoplastic agent is 7-ethyl-10-hydroxy-camptothecin (SN-38) claim 2 , irinotecan claim 2 , monomethyl auristatin E claim 2 , monomethyl auristatin F claim 2 , paclitaxel claim 2 , doxorubicin claim 2 , daunorubicin claim 2 , pyrrolobenzodiazepine claim 2 , 10-hydroxycamptothecin claim 2 , exatecan claim 2 , cyclopamine claim 2 , tacedinaline claim 2 , 5′-deoxy-5-fluorouridine claim 2 , 5-fluorouracil claim 2 , calicheamicine claim 2 , a maytansinoid claim 2 , maytansine claim 2 , methotrexate claim 2 , duocarmycin claim 2 , erlotinib claim 2 , gefitinib claim 2 , capecitabine claim 2 , leucovorin claim 2 , trifluridine claim 2 , tipiracil claim 2 , or CC-1065.4. The conjugate of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein the antineoplastic agent is SN-38 claim 2 , monomethyl auristatin E claim 2 , capecitabine claim 2 , 5′-deoxy-5-fluorouridine claim 2 , or 5-fluorouracil.5. The conjugate of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein the antineoplastic agent is SN-38.6. The conjugate of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein the antineoplastic agent is monomethyl auristatin E.7. The conjugate of claim 2 , or a pharmaceutically ...

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Номер записи: 63
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: 64
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: 65
26-05-2016 дата публикации

CYSTOBACTAMIDES

Номер: US20160145304A1
Автор: Baumann Sascha, Elgaher Walid A.M., Gerth Klaus, Gille Franziska, Hamed Mostafa, Hartmann Rolf, Herrmann Jennifer, Kirschning Andreas, Mohr Kathrin, MORENO Maria, Muller Rolf, Raju Ritesh, Steinmetz Heinrich, Wang Liang Liang
Принадлежит:

The present invention provides cystobactamides of formula (I) and the use thereof for the treatment or prophylaxis of bacterial infections: 9. A compound according to claim 7 , wherein{'sup': '1', 'Aris an optionally substituted 1,4-phenylene group or an optionally substituted 1,3-heteroarylene group having 5 ring atoms including 1, 2, or 3 heteroatoms selected from oxygen, sulphur and nitrogen;'}{'sup': '2', 'Aris an optionally substituted 1,4-phenylene group or an optionally substituted 1,3-heteroarylene group having 5 ring atoms including 1, 2, or 3 heteroatoms selected from oxygen, sulphur and nitrogen;'}{'sup': '3', 'Aris an optionally substituted 1,4-phenylene group or an optionally substituted 1,3-heteroarylene group having 5 ring atoms including 1, 2, or 3 heteroatoms selected from oxygen, sulphur and nitrogen;'}{'sup': '4', 'Aris absent or an optionally substituted 1,4-phenylene group or an optionally substituted 1,3-heteroarylene group having 5 ring atoms including 1, 2, or 3 heteroatoms selected from oxygen, sulphur and nitrogen; and'}{'sup': '5', 'Aris absent or an optionally substituted 1,4-phenylene group or an optionally substituted 1,3-heteroarylene group having 5 ring atoms including 1, 2, or 3 heteroatoms selected from oxygen, sulphur and nitrogen.'}10. A compound according to claim 7 , wherein{'sup': 1', '3', '4', '3', '4, 'sub': 2', '2', '1-6, 'Lis a group of formula —CONH—, —NHCO—, —SONH—, —NHSO—, —CH═CH—, —CR═CR— or an optionally substituted heteroarylene group having 5 ring atoms including 1, 2, or 3 heteroatoms selected from oxygen, sulphur and nitrogen, wherein Rand Rare independently from each other a Calkyl group;'}{'sup': 2', '3', '4', '3', '4, 'sub': 2', '2', '1-6, 'Lis a group of formula —CONH—, —NHCO—, —SONH—, —NHSO—, —CH═CH—, —CR═CR— or an optionally substituted heteroarylene group having 5 ring atoms including 1, 2, or 3 heteroatoms selected from oxygen, sulphur and nitrogen, wherein Rand Rare independently from each other a Calkyl ...

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Номер записи: 66
28-05-2015 дата публикации

GAMMA AMINO ACID BUILDING BLOCKS

Номер: US20150148523A1
Автор: GELLMAN Samuel Helmer, Giuliano Michael, Guo Li
Принадлежит: WISCONSIN ALUMNI RESEARCH FOUNDATION

The invention provides compounds and methods, for example, to carry out organocatalytic Michael additions of aldehydes to cyclically constrained nitroethylene compounds catalyzed by a proline derivative to provide cyclically constrained α-substituted-γ-nitro-aldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96 to >99% e.e.). 4. The compound of wherein Ris H or alkyl claim 3 , A-Aare each carbon claim 3 , Ris H or alkyl claim 3 , P is H claim 3 , methyl or acetyl claim 3 , and Y is nitro or protected amino.5. A method for preparing a compound of wherein Ris H comprising:contacting a cyclic compound of 5 or 6 ring atoms that includes a nitroethylene moiety within the ring and that optionally includes one or two nitrogen atoms in the ring, wherein the carbon atoms in the ring are optionally substituted and the optional nitrogen atom or atoms in the ring are optionally substituted by a nitrogen protecting group; andan aldehyde that has at least one α-hydrogen;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'in the presence of an organic solvent, and a proline derivative, for a period of time sufficient to provide the compound of .'}6. The method of wherein the aldehyde has an α-methylene group or an α-methine group.7. The method of wherein the contacting is carried out in the presence of a carboxylic acid claim 5 , the proline derivative is a chiral pyrrolidine catalyst claim 5 , and the compound of is prepared in at least about 80% enantiomeric purity.8. The method of further comprising reducing an aldehyde moiety of the compound of to an alcohol claim 5 , oxidizing the resulting alcohol to a carboxylic acid claim 5 , reducing the nitro moiety of the compound of to an amine claim 5 , or a combination thereof.12. The method of wherein the contacting is carried out in the presence of a carboxylic acid claim 11 , the proline derivative is a chiral ...

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Номер записи: 67
26-05-2016 дата публикации

COMPOSITIONS AND METHODS FOR THE DELIVERY OF NUCLEIC ACIDS

Номер: US20160145610A1
Автор: Gujrati Maneesh, Lu Zheng-Rong, Malamas Anthony
Принадлежит:

A compound comprising formula (I): 3. The compound of claim 1 , wherein Rand Rare independently a hydrophonic group derived from oleic acid or linoleic acid.4. The compound of claim 3 , wherein Rand Rare the same.5. The compound of claim 1 , wherein Rand Rare independently H claim 1 , a substituted or unsubstituted polymer claim 1 , a targeting group claim 1 , or a detectable moiety.6. The compound of claim 1 , wherein a claim 1 , b claim 1 , c claim 1 , and d are each 2.7. The compound of claim 1 , R1 comprises at least one of CHCHNH claim 1 , CHCHNHCHCHNHCHCHNH claim 1 , or CHCHNHCHCHCHCHNHCHCHCHNH.8. The compound of claim 1 , wherein the compound is ECO claim 1 , ECLn claim 1 , SHCO claim 1 , or SCLn.9. The compound of claim 1 , wherein polyethylene glycol is covalently attached to the compound.10. The compound of claim 1 , wherein the targeting group is covalently attached to the compound by a linker.11. The compound of claim 10 , wherein the linker comprises a polyamino acid group claim 10 , a polyalkylene group claim 10 , or a polyethyelene glycol group.12. The compound of claim 10 , wherein the targeting group comprises a peptide claim 10 , a protein claim 10 , an antibody claim 10 , or an antibody fragment.13. The compound of claim 11 , wherein the linker comprises an acid labide bond.14. A nanosized complex comprising a nucleic acid and compound of .15. The complex of claim 14 , wherein the nucleic acid comprises a natural or synthetic oligonucleotide claim 14 , a DNA or fragment thereof claim 14 , or an RNA or fragment thereof.16. The complex of claim 14 , wherein the nucleic acid comprises a siRNA or plasmid DNA.17. The complex of claim 14 , having an N/P ratio of at least about 6.18. The complex of claim 14 , further comprising a targeting group.19. The complex of claim 18 , wherein the targeting group is covalently attached to the compound by a linker.20. The complex of claim 19 , wherein the linker comprises a polyamino acid group claim 19 , a ...

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Номер записи: 68
31-05-2018 дата публикации

PRODRUGS OF PEPTIDE EPOXY KETONE PROTEASE INHIBITORS

Номер: US20180147291A1
Автор: Anik Shabbir T., By Kolbot, Luehr Gary W., Peng Ge, Phiasivongsa Pasit
Принадлежит:

This disclosure features compounds that are useful as pro-drugs of epoxy ketone protease inhibitors. 4. The compound according to any one of - , wherein M is CH.5. The compound according to any one of - , wherein said ring nitrogen atom is further substituted with a group R , thereby forming a quaternary nitrogen atom and wherein the positive charge associated with the quaternary nitrogen atom is balanced by a pharmaceutically acceptable anion.6. The compound of claim 5 , wherein Ris:{'sub': '2', 'sup': '15', '(i) —CHOC(═O)R;'}{'sub': '2', 'sup': '15', '(ii) —C(═O)OCHOC(═O)R;'}{'sup': '15', '(iii) —SR; or'}{'sub': '2', 'sup': '15', '(iv) —CHAr—R;'}wherein:{'sub': 6-10', '1-6', '1-6, 'Ar is Caryl, optionally substituted with from 1-3 substituents independently selected from Calkyl, Calkoxy, and halo;'}{'sup': '15', 'sub': 1-6', '1-6', '1-6', '1-6', '6-10', '7-12', '3-7', '1', '6', '1', '6, 'Ris Calkyl, Chaloalkyl, CalkoxyCalkyl, Caryl, Caralkyl, Ccycloalkyl, heteroaryl including from 5-10 ring atoms (wherein from 1-3 of the ring atoms are independently selected from N, NH, N—C-Calkyl, O, and S), or heterocyclyl including from 3-7 ring atoms (wherein from 1-2 of the ring atoms are independently selected from N, NH, N—C-Calkyl, and O), each of which is optionally substituted; or'}{'sup': '15', 'sub': 'n', 'Ris Y—Z; wherein{'sub': 6-10', '1', '6, 'Y is a divalent spacer comprising one or more of the following moieties (e.g., comprise 1, 2, 3, 4, or 5 of the following moieties; e.g., comprise 1, 2, or 3 of the following moieties; e.g., consist of 1, 2, 3, 4, or 5 of the following moieties; e.g., consist of 1, 2, or 3 of the following moieties): heteroatom (e.g., N, O, or S), alkylene chain, heteroalkylene chain, Carylene, heteroarylene from 5-10 ring atoms (wherein from 1-3 of the ring atoms are independently selected from N, NH, N—C-Calkyl, O, and S), polyheteroalkylene chain, alkenylene chain, —OC(═O)—, —C(═O)O—, —NHC(═O)—, —C(═O)NH—, —C(═O)—, cyclodextrin, human serum ...

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Номер записи: 69
07-05-2020 дата публикации

IBAT INHIBITORS FOR THE TREATMENT OF LIVER DISEASES

Номер: US20200140484A1
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)2. A method for decreasing the concentration of serum bile acids in a subject in need thereof , comprising orally administering to the subject a therapeutically effective amount of an IBAT inhibitor , wherein the IBAT inhibitor is 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 , or a pharmaceutically acceptable salt thereof.3. The method of claim 2 , wherein the subject is a pediatric subject.4. The method of claim 2 , wherein the subject has a disease selected from the group consisting of: Alagilles syndrome (ALGS) claim 2 , progressive familial intrahepatic cholestasis (PFIC) claim 2 , primary biliary cirrhosis (PBC) claim 2 , liver fibrosis claim 2 , non alcoholic fatty liver disease (NAFLD) claim 2 , non-alcoholic steatohepatitis (NASH) claim 2 , primary sclerosing cholangitis (PSC) claim 2 , intrahepatic cholestasis claim 2 , and extrahepatic cholestasis claim 2 , and combinations thereof.5. The method of claim 4 , wherein the subject has PFIC.6. The method of claim 4 , wherein the subject has ALGS.7. The method of claim 4 , wherein the subject has intrahepatic cholestasis.8. The method of claim 4 , wherein the subject has extrahepatic cholestasis.9. The method of claim 4 , wherein the subject has pruritus as a comorbidity.10. The method of claim 4 , wherein the subject has pruritus as a symptom of the disease.11. The method of claim 2 , further comprising administering a therapeutically effective amount of a bile acid binder.12. The method of claim 11 , wherein the bile acid binder is a resin.13. The method of claim 12 , wherein the resin is ...

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Номер записи: 70
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: 71
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: 72
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: 73
23-05-2019 дата публикации

NMDA ANTAGONIST PRODRUGS

Номер: US20190152914A1
Автор: Balestra Michael, Bernstein Peter Robert, HÖGDIN Katharina, KERS Annika, Malmborg Per Jonas, NORDVALL Gunnar, Quirk Michael, Weigelt Dirk Reinhold
Принадлежит:

Prodrugs of an NMDA antagonist, (S)-1-phenyl-2-(pyridin-2-yl)ethanamine, useful for the treatment of depression (particularly major depressive disorder) or pain; compositions comprising them, and methods of making them. 118-. (canceled)19. A pharmaceutical composition comprising from 0.10 to 50% by weight of compound that is (S)-1-((S)-2-amino-3-methylbutanoyl)-N-((S)-1-phenyl-2-(pyridin-2-yl)ethyl)pyrrolidine-2-carboxamide , or a pharmaceutically acceptable salt thereof , and a pharmaceutically acceptable carrier.20. The pharmaceutical composition of wherein the compound is (S)-1-((S)-2-amino-3-methylbutanoyl)-N-((S)-1-phenyl-2-(pyridin-2-yl)ethyl)pyrrolidine-2-carboxamide dihydrochloride salt.21. The pharmaceutical composition of wherein the compound is (S)-1-((S)-2-amino-3-methylbutanoyl)-N-((S)-1-phenyl-2-(pyridin-2-yl)ethyl)pyrrolidine-2-carboxamide fumarate salt.22. The pharmaceutical composition of wherein the carrier is selected from lactose claim 19 , saccharose claim 19 , sorbitol claim 19 , mannitol; a starch claim 19 , and a cellulose derivative.23. The pharmaceutical composition of which further comprises a binder.24. The pharmaceutical composition of wherein the binder is selected from gelatin and polyvinylpyrrolidone.25. The pharmaceutical composition of which further comprises a lubricant.26. The pharmaceutical composition of wherein the lubricant is selected from magnesium stearate claim 24 , calcium stearate claim 24 , polyethylene glycol and a wax.27. The pharmaceutical composition of in the form of a tablet.28. The pharmaceutical composition of wherein the tablet has a coating.29. The pharmaceutical composition of wherein the coating contains gum arabic claim 28 , gelatine claim 28 , talcum or titanium dioxide.30. The pharmaceutical composition of in the form of a soft gelatine capsule.31. The pharmaceutical composition of wherein the soft gelatine capsule contains a vegetable oil or polyethylene glycol.32. The pharmaceutical composition of in ...

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Номер записи: 74
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: 75
14-06-2018 дата публикации

IBAT INHIBITORS FOR THE TREATMENT OF LIVER DISEASES

Номер: US20180162904A1
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)2. A method for treating a bile acid dependent disease which impacts at least the extrahepatic or intrahepatic biliary tree in a subject , the method comprising orally administering to a subject in need of such treatment a therapeutically effective amount an IBAT inhibitor , wherein the IBAT inhibitor is 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 , or a pharmaceutically acceptable salt thereof.3. The method of claim 2 , wherein the bile acid dependent disease impacts at least the extrahepatic biliary tree in the subject.4. The method of claim 2 , wherein treatment of the bile acid disease comprises treatment of pruritus.5. The method of claim 2 , wherein treatment of the bile acid disease comprises treatment of one or more of Alagilles syndrome (ALGS) claim 2 , progressive familial intrahepatic cholestasis (PFIC) claim 2 , or intra- and extrahepatic cholestasis.6. The method of claim 2 , wherein treatment of the bile acid disease comprises decreasing the level of serum bile acids in the subject.7. The method of claim 2 , wherein treatment of the bile acid disease comprises decreasing the level of liver bile acids in the subject.8. The method of claim 2 , wherein the bile acid dependent disease is a malignancy causing obstruction of the biliary tree.9. The method of claim 2 , wherein the subject is a pediatric subject. Ileal bile acid transporter (IBAT) is the main mechanism for re-absorption of bile acids from the GI tract. Partial or full blockade of that mechanism will result in lower concentration of bile acids in the small bowel wall, portal ...

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Номер записи: 76
15-06-2017 дата публикации

Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of asgpr

Номер: US20170165284A1
Автор: Benjamin Thuma, Spiros Liras, Vincent Mascitti
Принадлежит: PFIZER INC

Compounds of Formula (A) are described herein and the uses thereof for the treatment of diseases, conditions and/or disorders mediated by pharmaceutical compositions and the uses thereof as asialoglycoprotein receptor (ASGPR) targeting agents.

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Номер записи: 77
01-07-2021 дата публикации

HEMIASTERLIN DERIVATIVES FOR CONJUGATION AND THERAPY

Номер: US20210198314A1
Автор: Bajjuri Krishna, KLINE Toni, Yin Qun
Принадлежит:

Provided herein are hemiasterlin derivatives, conjugates thereof, compositions comprising the derivatives or conjugates thereof, methods of producing the derivatives and conjugates thereof, and methods of using the derivatives, conjugates, and compositions for the treatment of cell proliferation. The derivatives, conjugates, and compositions are useful in methods of treatment and prevention of cell proliferation and cancer, methods of detection of cell proliferation and cancer, and methods of diagnosis of cell proliferation and cancer. In an embodiment, the hemiasterlin derivatives are according to Formula 1000: 224-. (canceled)25. The compound of claim 1 , wherein Ar is a divalent five- or six-membered claim 1 , substituted or unsubstituted claim 1 , monocyclic heteroaryl claim 1 , or a pharmaceutically acceptable salt claim 1 , or tautomer thereof.26. The compound of claim 1 , wherein Ar is a divalent six-membered claim 1 , substituted or unsubstituted claim 1 , monocyclic aryl claim 1 , or a pharmaceutically acceptable salt claim 1 , or tautomer thereof.27. The compound of claim 1 , wherein Ar is a divalent ten-membered claim 1 , substituted or unsubstituted claim 1 , fused bicyclic aryl; or a divalent eight- claim 1 , nine- or ten-membered claim 1 , substituted or unsubstituted claim 1 , fused bicyclic heteroaryl claim 1 , or a pharmaceutically acceptable salt claim 1 , or tautomer thereof.28. The compound of claim 1 , wherein Ar is a divalent nine-membered claim 1 , substituted or unsubstituted claim 1 , fused bicyclic heteroaryl claim 1 , or a pharmaceutically acceptable salt claim 1 , or tautomer thereof.30. The compound of claim 1 , wherein L is absent claim 1 , or a pharmaceutically acceptable salt claim 1 , or tautomer thereof.31. The compound of claim 1 , wherein L is —CH— claim 1 , or a pharmaceutically acceptable salt claim 1 , or tautomer thereof.32. (canceled)34. (canceled)3665-. (canceled)66. A pharmaceutical composition comprising the compound of ...

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Номер записи: 78
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: 79
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: 80
29-06-2017 дата публикации

IBAT Inhibitors for the Treatment of Liver Disease

Номер: US20170182059A1
Автор: Hans Graffner, Ingemar Starke, Per-Goran Gillberg
Принадлежит: ALBIREO AB

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.

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Номер записи: 81
09-07-2015 дата публикации

Polymorphs of n-[(r)-1-[(s)-1-(4-aminomethyl-benzylcarbamoyl)-2-phenyl-ethylcarbamoyl]-2-(4-ethoxy-phenyl)-ethyl]-benzamide hydrochloride

Номер: US20150191421A1
Автор: John Mykytiuk, Julian Scott Northen
Принадлежит: Kalvista Pharmaceuticals Ltd

The invention provides new polymorphs of N—[(R)-1-[(S)-1-(4-aminomethyl-benzylcarbamoyl)-2-phenyl-ethylcarbamoyl]-2-(4-ethoxy-phenyl)-ethyl]-benzamide hydrochloride, pharmaceutical compositions containing them and their use in therapy.

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Номер записи: 82
04-06-2020 дата публикации

PROCESS FOR THE LIQUID PHASE SYNTHESIS OF H-INP-(D)BAL-(D)TRP-PHE-APC-NH2, AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

Номер: US20200172572A1
Автор: Decroos Karel, Titeux Olivier
Принадлежит:

The present invention provides a process for the liquid phase synthesis of the Ghrelin analog H-Inp-(D)Bal-(D)Trp-Phe-Apc-NH(SEQ ID NO: 1, Formula (I)), pharmaceutically acceptable salts thereof. 1. A process for the synthesis of a peptide of Formula (I){'br': None, 'sub': '2', 'H-Inp-(D)Bal-(D)Trp-Phe-Apc-NH, \u2003\u2003(I)'}or pharmaceutically acceptable salt thereof, comprising at least one step of coupling any two amino acids of the peptide of Formula (I) in a liquid phase.2. The process of claim 1 , further comprising a step of reacting a silylating agent with a first amino acid selected form the amino acids of the peptide of Formula (I) in a polar aprotic organic solvent claim 1 , thereby producing a first silylated amino acid.3. The process of claim 2 , further comprising at least one step of coupling the first silylated amino acid with a second amino acid selected from the amino acids of the peptide of Formula (I).4. The process of any one of to claim 2 , comprising the step of reacting a silylating agent with the amino acid H-(D)Trp-OH in a polar aprotic organic solvent claim 2 , thereby forming a silylated amino acid residue of the amino acid H-(D)Trp-OH or a salt thereof.5. The process of claim 4 , further comprising the step of reacting the silylated amino acid residue of the amino acid H-(D)Trp-OH with an amino acid of the following formula{'br': None, 'sup': 1', '1, 'X-(D)Bal-Y,'} {'br': None, 'sup': '1', 'X-(D)Bal-(D)Trp-OH,'}, 'thereby producing a peptide fragment of the following formula'}or a salt thereof,{'sup': 1', '1, 'wherein Xis an amino protecting group, and Yis a carboxyl activating group.'}6. The process of any one of to claim 4 , comprising the step of reacting a silylating agent with the amino acid H-Apc(X)—OH in a polar aprotic organic solvent claim 4 , thereby forming a silylated amino acid residue of the amino acid H-Apc(X)—OH or a salt thereof claim 4 , wherein Xis an amino protecting group.8. The process of claim 7 , further ...

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Номер записи: 83
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: 84
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: 85
06-07-2017 дата публикации

MACROCYCLIC INHIBITORS OF FLAVIVIRIDAE VIRUSES

Номер: US20170190737A1
Автор: Aciro Caroline, Dean David Kenneth, Dunbar Neil Andrew, Highton Adrian John, Jansa Petr, Karki Kapil Kumar, Keats Andrew John, Lazarides Linos, Mackman Richard L., Pettit Simon N., Poullennec Karine G., Schrier Adam James, Siegel Dustin, Steadman Victoria Alexandra
Принадлежит:

Provided are compounds of Formula I: 2. The compound of claim 1 , wherein Ais ethenylene claim 1 , propenylene claim 1 , butenylene claim 1 , ethylene claim 1 , propylene claim 1 , butylene claim 1 , oxypropylene claim 1 , oxypropenylene claim 1 , pyrazolylene claim 1 , phenylene claim 1 , pyridylene or pyrimidinylene.3. The compound of claim 1 , wherein Ais isoquinolinylene claim 1 , phenylene or halophenylene.4. The compound of claim 1 , wherein Xis —O— or —NH—; one of Rand Ris H and the other is methyl; Ris iso-propyl; Ris methyl and Ris H or methyl.5. The compound of claim 1 , wherein Ris H or methyl; Ris H; Ris H claim 1 , —OH claim 1 , methoxy claim 1 , trifluoroethoxy; and Ris H.7. The compound of claim 1 , wherein Ais heteroarylene; Ais (C-C)alkylene claim 1 , (C-C)alkenylene claim 1 , (C-C)alkynylene claim 1 , wherein Ais optionally substituted with one or more (C-C)alkyl; Ris H or methyl; and Ris H claim 1 , —OH or (C-C)alkoxy.8. (canceled)9. The compound of claim 1 , wherein Ais arylene;{'sup': 1', '1', '3a', '4a, 'sub': 2', '5', '2', '5', '2', '5', '2', '5', '2', '4', '1', '4', '1', '4', '1', '4, 'and Ais (C-C)alkylene, (C-C)alkenylene, (C-C)alkynylene, —O—(C-C)alkylene, —O—(C-C)alkenylene, wherein Ais optionally substituted with one or more (C-C)alkyl; Ris H or methyl; and Ris H, —OH, (C-C)alkoxy or halo(C-C)alkoxy.'}11. The compound of claim 1 , wherein Ais arylene; and Ais pyrazolylene claim 1 , phenylene or pyridylene.12. (canceled)13. The compound of claim 1 , wherein Ais halophenylene; and Ais —O—(C-C)alkylene or —O—(C-C)alkenylene.14. (canceled)17. A pharmaceutical composition comprising a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , isotope claim 1 , stereoisomer claim 1 , mixture of stereoisomers claim 1 , tautomer claim 1 , ester or prodrug thereof and a pharmaceutically acceptable excipient.18. The pharmaceutical composition of claim 17 , further comprising at least one additional ...

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Номер записи: 86
20-06-2019 дата публикации

CYSTOBACTAMIDES

Номер: US20190185514A1
Автор: Baumann Sascha, Elgaher Walid A. M., Gerth Klaus, Gille Franziska, Hamed Mostafa, Hartmann Rolf W., Herrmann Jennifer, Hüttel Stephan, Kirschning Andreas, Mohr Kathrin, MORENO Maria, Muller Rolf, Raju Ritesh, Steinmetz Heinrich, Wang Liang Liang
Принадлежит:

The present invention provides cystobactamides of formula (I) and the use thereof for the treatment or prophylaxis of bacterial infections: 7. A compound of formula (I){'br': None, 'sup': 1', '1', '1', '2', '2', '3', '3', '4', '4', '5', '2, 'R—Ar-L-Ar-L-Ar-L-Ar-L-Ar—R\u2003\u2003 (I)'}wherein{'sup': '1', 'Aris an optionally substituted phenylene group or an optionally substituted heteroarylene group having 5 or 6 ring atoms including 1, 2, 3 or 4 heteroatoms selected from oxygen, sulphur and nitrogen;'}{'sup': '2', 'Aris an optionally substituted phenylene group or an optionally substituted heteroarylene group having 5 or 6 ring atoms including 1, 2, 3 or 4 heteroatoms selected from oxygen, sulphur and nitrogen;'}{'sup': '3', 'Aris an optionally substituted phenylene group or an optionally substituted heteroarylene group having 5 or 6 ring atoms including 1, 2, 3 or 4 heteroatoms selected from oxygen, sulphur and nitrogen;'}{'sup': '4', 'Aris absent or an optionally substituted phenylene group or an optionally substituted heteroarylene group having 5 or 6 ring atoms including 1, 2, 3 or 4 heteroatoms selected from oxygen, sulphur and nitrogen;'}{'sup': '5', 'Aris absent or an optionally substituted phenylene group or an optionally substituted heteroarylene group having 5 or 6 ring atoms including 1, 2, 3 or 4 heteroatoms selected from oxygen, sulphur and nitrogen;'}{'sup': 1', '3', '3', '3', '3', '3', '4', '3', '3', '3', '3', '3', '4', '3', '4', '3', '4', '3', '4, 'sub': 2', '2', '2', '2', '2', '2', '2, 'Lis a bond, an oxygen atom, a sulphur atom or a group of formula NH, CONH, NHCO, COO, OCO, CONR, NRCO, OCONH, NHCOO, NHCONH, OCONR, NRCOO, NRCONR, NR, —CNR—, —CO—, —SO—, —SO—, —SONH—, —NHSO—, —SONR—, —NRSO—, —COCH—, —CHCO—, —COCRR—, —CRRCO—, —NHCSNH—, —NRCSNR, —CH═CH—, —CR═CR—, or a heteroarylene group having 5 or 6 ring atoms including 1, 2, or 3 heteroatoms selected from oxygen, sulphur and nitrogen, or a heteroalkylene group;'}{'sup': 2', '3', '3', '3', '3', '3', ...

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Номер записи: 87
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: 88
12-07-2018 дата публикации

THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE

Номер: US20180194802A1
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: 89
21-07-2016 дата публикации

SUBSTITUTED-6,8-DIOXABICYCLO[3.2.1]OCTANE-2,3-DIOL COMPOUNDS AS TARGETING AGENTS OF ASGPR

Номер: US20160207953A1
Автор: Liras Spiros, Mascitti Vincent, Thuma Benjamin
Принадлежит: PFIZER INC.

Compounds of Formula (A) are described herein and the uses thereof for the treatment of diseases, conditions and/or disorders mediated by pharmaceutical compositions and the uses thereof as asialoglycoprotein receptor (ASGPR) targeting agents. 3. The compound of or or a pharmaceutically acceptable salt thereof , wherein Ris —X—Y , and Ris —NH—C(O)—CH.4. The compound of or or a pharmaceutically acceptable salt thereof , wherein Y is a protein , plasmid or an siRNA sequence.5. The compound of or a pharmaceutically acceptable salt thereof claim 3 , wherein Y is a Cas9 ribonucleoprotein claim 3 , cas9 protein claim 3 , or plasmid.6. The compound of or or a pharmaceutically acceptable salt thereof claim 3 , wherein the compound of Formula (A) is capable of binding to a receptor present on a hepatocyte.7. The compound of or a pharmaceutically acceptable salt thereof claim 5 , wherein the receptor present on a hepatocyte is an asialoglycoprotein receptor.8. A pharmaceutical composition comprising (i) a compound of ; or a pharmaceutically acceptable salt thereof; and (ii) a pharmaceutically acceptable excipient claim 6 , diluent claim 6 , or carrier.9. The composition of wherein said compound or said therapeutically acceptable salt thereof is present in a therapeutically effective amount.10. A method for treating a liver disease or condition or a liver modulated disease or condition claim 7 , comprising the administration of an effective amount of a compound according to any of or or a pharmaceutically acceptable salt thereof.11. The method of wherein the liver disease or condition or liver modulated disease or condition is selected from the group consisting of: hereditary angioedema claim 10 , familial tyrosinemia type I claim 10 , Alagille syndrome claim 10 , Alpha-1-antitrypsin deficiency claim 10 , Bile acid synthesis and metabolism defects claim 10 , Biliary Atresia claim 10 , Cystic Fibrosis liver disease claim 10 , Idiopathic neonatal hepatitis claim 10 , ...

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Номер записи: 90
21-07-2016 дата публикации

METHOD FOR PRODUCING DIPEPTIDE DERIVATIVE CONTAINING DISUBSTITUTED AMINO ACID RESIDUE

Номер: US20160207958A1
Автор: Kodama Kazuya, Matsuyama Keisuke
Принадлежит: NAGASE & CO., LTD.

A method for producing a dipeptide that has a protected N-terminal and is represented by formula (1) or a salt of the dipeptide, said method comprising condensing an α-monosubstituted amino acid that has a protected N-terminal and is represented by formula (2) or glycine or a salt thereof with a disubstituted amino acid that is represented by formula (3) or a salt thereof in the presence of a condensing agent [in each of the formulae, substituents are as defined in the description or the like]. 2. The production method according to claim 1 , wherein the N-terminal protected α-monosubstituted amino acid or glycine represented by the formula (2) claim 1 , or a salt of the amino acid or glycine is condensed with the disubstituted amino acid represented by the formula (3) or a salt thereof in the presence of a stoichiometric amount or more of the condensing agent.3. The production method according to claim 1 , wherein the reaction of the N-terminal protected α-monosubstituted amino acid or glycine represented by the formula (2) claim 1 , or a salt of the amino acid or glycine with the disubstituted amino acid represented by the formula (3) or a salt thereof is terminated when the rate of reaction of the N-terminal protected α-monosubstituted amino acid or glycine represented by the formula (2) claim 1 , or a salt of the amino acid or glycine reaches 70 to 80%.4. The production method according to claim 2 , wherein the reaction of the N-terminal protected α-monosubstituted amino acid or glycine represented by the formula (2) claim 2 , or a salt of the amino acid or glycine with the disubstituted amino acid represented by the formula (3) or a salt thereof is terminated when the rate of reaction of the N-terminal protected α-monosubstituted amino acid or glycine represented by the formula (2) claim 2 , or a salt of the amino acid or glycine reaches 70 to 80%. The present invention relates to a method for producing a dipeptide derivative containing a disubstituted amino ...

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Номер записи: 91
20-07-2017 дата публикации

Disulfur bridge linkers for conjugation of a cell-binding molecule

Номер: US20170202975A1
Автор: Robert Yongxin Zhao
Принадлежит: Sushou M conj Biotech Co Ltd

The present invention relates to novel disulfur bridge linkers containing hydrazine used for the specific conjugation of compounds/cytotoxic agents to a cell-binding molecule, through bridge linking a pair of thiols on the cell-binding molecule. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.

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Номер записи: 92
27-07-2017 дата публикации

Formation of organic nanostructure array

Номер: US20170209845A1
Автор: Ehud Gazit, Meital Reches
Принадлежит: Ramot at Tel Aviv University Ltd

A nanostructure array is disclosed. The nanostructure array comprises a plurality of elongated organic nanostructures arranged generally perpendicularly to a plane.

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Номер записи: 93
09-10-2014 дата публикации

N-ACYLDIPEPTIDE DERIVATIVES AND THEIR USES

Номер: US20140303080A1
Автор: VAN SCOTT Eugene J., YU Ruey J.
Принадлежит:

N-acyldipeptide derivatives are described. Compositions comprising the N-acyldipeptide derivatives are therapeutically effective for topical or systemic administration to alleviate or improve conditions, disorders, diseases, symptoms or syndromes associated with a tumor, cancer, immune, nervous, vascular, musculoskeletal or cutaneous system, or other tissue or system in a subject. 1. A composition for topical or systemic administration to a mammal comprising a pharmaceutically or cosmetically acceptable carrier and a therapeutically effective amount of a dipeptide derivative having the following generic Formula (I):{'br': None, 'sub': 1', '2, 'R-AAB-AAC-R\u2003\u2003Formula (I)'}or an isomer, free acid, base, salt, lactone, amide, hydrazide, or ester thereof,{'sub': 1', '2', '3', '4', '5', '3', '4', '5', '2', '2', '2', '2', '2, 'wherein Ris an acyl radical having up to 19 carbon atoms; AAB is an amino terminal amino acid residue selected from any amino acid; AAC is a carboxyl terminal amino acid residue selected from any amino acid; Ris OR, NHRor NHNHR; Ris H, an alkyl, aralkyl or aryl radical having up to 19 carbon atoms; Ror Ris independently H, OH, an alkyl, aralkyl, aryl or acyl radical having up to 19 carbon atoms; a side chain of each of AAB and AAC optionally and independently has an extra functional radical selected from the group consisting of OH, SH, NHCONH, NHC(═NH)NH, NH, COOH, CONH, imidazolyl, pyrrolidinyl and indolyl; and the H or OH of the extra functional radical is optionally substituted by NH, an acyl, alkyl, aralkyl, or aryl radical having up to 19 carbon atoms.'}2. The composition of claim 1 , wherein the AAB is an amino terminal amino acid residue selected from the group consisting of Ala claim 1 , βAla claim 1 , Abz claim 1 , Asn claim 1 , Cre claim 1 , Cys claim 1 , Dopa claim 1 , Gly claim 1 , Gln claim 1 , Glu claim 1 , Gaba claim 1 , His claim 1 , Hpg claim 1 , Ile claim 1 , Leu claim 1 , Pgly claim 1 , Phe claim 1 , Pro claim 1 , Ser ...

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Номер записи: 94
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: 95
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: 96
03-08-2017 дата публикации

PROCESS FOR THE LIQUID PHASE SYNTHESIS OF H-INP-(D)BAL-(D)TRP-PHE-APC-NH2, AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

Номер: US20170218015A1
Автор: Decroos Karel, Titeux Olivier
Принадлежит:

The present invention provides a process for the liquid phase synthesis of the Ghrelin analog H-Inp-(D)Bal-(D)Trp-Phe-Apc-NH2 (SEQ ID NO: 1, Formula (I)), pharmaceutically acceptable salts thereof. 1. A process for the synthesis of a peptide of Formula (I){'br': None, 'sub': '2', 'H-Inp-(D)Bal-(D)Trp-Phe-Apc-NH,\u2003\u2003(I)'}or pharmaceutically acceptable salt thereof, comprising at least one step of coupling any two amino acids of the peptide of Formula (I) in a liquid phase.2. The process of claim 1 , further comprising a step of reacting a silylating agent with a first amino acid selected form the amino acids of the peptide of Formula (I) in a polar aprotic organic solvent claim 1 , thereby producing a first silylated amino acid.3. The process of claim 2 , further comprising at least one step of coupling the first silylated amino acid with a second amino acid selected from the amino acids of the peptide of Formula (I).4. The process of any one of to claim 2 , comprising the step of reacting a silylating agent with the amino acid H-(D)Trp-OH in a polar aprotic organic solvent claim 2 , thereby forming a silylated amino acid residue of the amino acid H-(D)Trp-OH or a salt thereof.5. The process of claim 4 , further comprising the step of reacting the silylated amino acid residue of the amino acid H-(D)Trp-OH with an amino acid of the following formula{'br': None, 'sup': 1', '1, 'X-(D)Bal-Y,'} {'br': None, 'sup': '1', 'X-(D)Bal-(D)Trp-OH,'}, 'thereby producing a peptide fragment of the following formula'}or a salt thereof,{'sup': 1', '1, 'wherein Xis an amino protecting group, and Yis a carboxyl activating group.'}6. The process of any one of to claim 4 , comprising the step of reacting a silylating agent with the amino acid H-Apc(X)—OH in a polar aprotic organic solvent claim 4 , thereby forming a silylated amino acid residue of the amino acid H-Apc(X)—OH or a salt thereof claim 4 , wherein Xis an amino protecting group.7. The process of claim 6 , further ...

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Номер записи: 97
16-10-2014 дата публикации

Hemiasterlin derivatives and uses thereof in the treatment of cancer

Номер: US20140309174A1
Автор: Boris M. Seletsky, Galina Kuznetsov, Hu Yang, James J. Kowalczyk, Mark Spyvee, Shawn Schiller
Принадлежит: Eisai Co Ltd

The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R 1 -R 7 , X 1 , X 2 , R, Q, and n are as defined herein.

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Номер записи: 98
02-07-2020 дата публикации

TRIPEPTIDE EPOXY KETONE PROTEASE INHIBITORS

Номер: US20200207809A1
Автор: Bowers Simeon, JOHNSON Henry, McMinn Dustin, Moebius David C.
Принадлежит:

Provided herein are tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X): 2. The compound of claim 1 , wherein m is 0.3. The compound of claim 1 , wherein m is 1.4. The compound of claim 1 , wherein m is 2.5. The compound of any one of to claim 1 , wherein n is 2.6. The compound of claim 1 , claim 1 , or claim 1 , wherein n is 1.7. The compound of or claim 1 , wherein n is 0.8. The compound of any one of to claim 1 , wherein p is 0.9. The compound of any one of to claim 1 , wherein p is 1.10. The compound of any one of to claim 1 , wherein q is 0.11. The compound of any one of to claim 1 , wherein q is 1.12. The compound of any one of to claim 1 , wherein q is 2.13. The compound of any one of to claim 1 , wherein K is CRR.15. The compound of any one of to claim 1 , wherein K is NR.16. The compound of claim 15 , wherein K is NCHor NCHCH.17. The compound of any one of to claim 15 , wherein K is N(C═O)OR claim 15 , —NH—(C═O)— claim 15 , S claim 15 , SO claim 15 , or SO.18. The compound of any one of to claim 15 , wherein K is O.19. The compound of any one of to claim 15 , wherein E is N.20. The compound of any one of to claim 15 , wherein E is CR.21. The compound of claim 20 , wherein E is CH or C(CH).24. The compound of any one of to claim 20 , wherein Ris Calkyl.25. The compound of claim 24 , wherein Ris Calkyl.26. The compound of any one of to claim 24 , wherein Ris CH claim 24 , CHOH claim 24 , CF claim 24 , CH(OH)CH claim 24 , CHCN claim 24 , or CHCH.27. The compound of claim 26 , wherein Ris CH claim 26 , CHOH claim 26 , CH(OH)CH claim 26 , CHCN.28. The compound of any one of to claim 26 , wherein Ris Calkenyl or Calkynyl.29. The compound of claim 28 , wherein Ris CHCCH.30. The compound of any one of to claim 28 , wherein Ris Ccycloalkyl.31. The compound of claim 30 , wherein Ris cyclopropyl claim 30 , cyclobutyl ...

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Номер записи: 99
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: 100