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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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Форма поиска

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 1733. Отображено 100.
24-05-2012 дата публикации

Dual-acting antihypertensive agents

Номер: US20120129900A1
Автор: Daniel Marquess, Keith Jendza, Paul R. Fatheree, Robert M. McKinnell, Ryan Hudson, Seok-Ki Choi, Sharath Hegde, Vivek Sasikumar
Принадлежит: Theravance Inc

The invention is directed to compounds of formula I: wherein Ar, r, R 3 , X, and R 5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula I have AT 1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and a process and intermediates for preparing such compounds.

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Номер записи: 1
07-06-2012 дата публикации

Antagonists of the Magnesium Binding Defect as Therapeutic Agents and Methods for Treatment of Abnormal Physiological States

Номер: US20120142781A1
Автор: Ibert Clifton Wells
Принадлежит: Magnesium Diagnostics Inc

This invention provides a class of therapeutic compounds and methods for the treatment of mammals with physiological disorders, such as for example a frequently occurring type of essential hypertension, which are critically associated with the decreased binding of magnesium to the plasma membranes of their cells. These methods consist of administering to a mammal in need of such treatment a compound selected from a series of disubstituted trans, trans 1,3-butadienes, 1,3-disubstituted perhydrobutadienes, 1,2-disubstituted trans ethylenes and 1,2 disubstituted ethanes and disubstituted propanes, each of which embodies, in common, the unique structural feature essential for the biological activity of these compounds. This invention also provides for pharmaceutical formulations that employ these novel compounds.

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Номер записи: 2
14-06-2012 дата публикации

Enzyme inhibitors

Номер: US20120149736A1
Автор: Alastair David Graham Donald, Andrew James Belfield, Carl Leslie North, David Festus Charles Moffat, Stewart Andrew Wayne Jones
Принадлежит: Chroma Therapeutics Ltd

Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent ═CH— or ═N—; W is —CH═CH— Or —CH 2 CH 2 —; R 1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intra-cellular carboxylesterase enzymes to a carboxylic acid group; R2 and R3 are selected from the side chains of a natural or non-nat-ural alpha amino acid, provided that neither R2 nor R3 is hydrogen, or R2 and R3, taken together with the carbon to which they are attached, form a 3-6 membered saturated cycloalkyl or heterocyclyl ring; Y is a bond, —C(═O)—, —S(═O)2—, —C(═O)O—, —C(═O)NR′—, —C(═5)—NR′, —C(═NH)NR′ or —S(═O) 2 NR — wherein R′ is hydrogen or optionally substituted C 1 —C 6 alkyl; L 1 is a divalent radical of formula —(Alk 1 ) m ,(Q) n (Alk 2 ) p — wherein m, n, p, Q, Alk 1 and Alk 2 are as defined in the claims; X 1 represents a bond; —C(═O); or —S(═O) 2 —; —NR 4 C(═O)—, —C(═O)NR 4 —,— NR 4 C(═O)NR 5 —, —NR 4 S(═O) 2 —, or —S(═O) 2 NR 4 — wherein R4 and R5 are independently hydrogen or optionally substituted C 1 -C 6 alkyl; and z is 0 or 1.

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Номер записи: 3
30-08-2012 дата публикации

2-phenylethylamino derivatives as calcium and/or sodium channel modulators

Номер: US20120220592A1
Автор: Alessandra Restivo, Carla Caccia, Cibele Sabido-David, Ermanno Moriggi, Florian Thaler, Laura Faravelli, Mauro Napoletano, Patricia Salvati
Принадлежит: Newron Pharmaceuticals SpA

2-Phenylethylamino substituted carboxamide derivatives and their use as sodium and/or calcium channel modulators useful in preventing, alleviating and curing a wide range of pathologies are presented.

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Номер записи: 4
07-02-2013 дата публикации

Therapeutic peptides

Номер: US20130035296A1
Автор: Martina Havelkova, Morten STRØM, Terkel Hansen, Veronika TØRFOSS
Принадлежит: LYTIX BIOPHARMA AS

The present invention provides a peptide, peptidomimetic or amino acid derivative having a net positive charge of at least +2 and incorporating a disubstituted β amino acid, each of the substituting groups in the β amino acid, which may be the same or different, comprises at least (7) non-hydrogen atoms, is lipophilic and has at least one cyclic group, one or more cyclic groups within a substituting group may be linked or fused to one or more cyclic groups within the other substituting group and where cyclic groups are fused in this way the combined total number of non-hydrogen atoms for the two substituting groups is at least (12), for use as a cytolytic therapeutic agent; as well as non therapeutic uses of these molecules and certain defined novel compounds from within this definition.

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Номер записи: 5
28-03-2013 дата публикации

"OMEGA-AMINOALKYLAMIDES OF R-2-ARYL-PROPIONIC ACIDS AS INHIBITORS OF THE CHEMOTAXIS OF POLYMORPHONUCLEATE AND MONONUCLEATE CELLS"

Номер: US20130079514A1
Автор: Allegretti Marcello, Berdini Valerio, Bertini Riccardo, BIZZARRI Cinzia, CASELLI Gianfranco, CESTA Maria Candida, Colotta Francesco, DI CIOCCIO Vito, GANDOLFI Carmelo
Принадлежит: Dompé S.p.A.

(R)-2-Arylpropionamide compounds of formula (I), pharmaceutical preparations of the compounds and a process for making the compounds are described. 2. The composition claim according to claim 1 , wherein the compound of the formula I has activity as an inhibitor of IL-8 induced chemotaxis of polymorphonucleate leukocytes.3. The composition of claim 1 , containing said compound in an amount effective for the treatment of a pathology selected from the group consisting of psoriasis claim 1 , pemphigus and pemphigoid claim 1 , rheumatoid arthritis claim 1 , intestinal chronic inflammatory pathologies claim 1 , acute respiratory distress syndrome claim 1 , idiopathic fibrosis claim 1 , cystic fibrosis claim 1 , chronic obstructive pulmonary disease and glomerulonephritis.4. The composition of claim 1 , wherein X together with the nitrogen atom of the omega-amino group to which it is bound and with the R1 and R2 groups forms a non-aromatic nitrogen containing ring selected from 1-methyl-piperydin-4-yl and N-exo-8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl.5. The composition according to claim 1 , wherein said compound of formula (I) is selected from the group consisting of(R)-2-[(4-isobutyl)phenyl]-N-(1-methylpiperidin-4-yl)propionamide;(R)-2-[(4-isobutyl)phenyl]-N(exo-8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)propionamide. This application is a Divisional application that claims priority under 35 U.S.C. §120 of application Ser. No. 10/469,094 filed on Aug. 25, 2003, and application Ser. No. 10/469,094 is the National Phase under 35 U.S.C. §371 of International Application No. PCT/EP2002/001974 filed on Feb. 25, 2002, which claims priority under 35 U.S.C. §119(a-d) of Application No. MI2001A000395 filed in the Italian Patent Office on Feb. 27, 2001. All of these applications are hereby incorporated by reference for all purposes.The present invention relates to omega-aminoalkylamides of (R) 2-aryl-propionic acids as inhibitors of the chemotaxis of polymorphonucleate and mononucleate ...

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Номер записи: 6
02-05-2013 дата публикации

HAPTEN CONJUGATES FOR TARGET DETECTION

Номер: US20130109019A1
Автор: Bieniarz Christopher, Day William, Kosmeder Jerome W., Lefever Mark, May Eric, Miller Phillip, Murillo Adrian E., Pedata Anne M.
Принадлежит:

Embodiments of hapten conjugates including a hapten, an optional linker, and a peroxidase-activatable aryl moiety are disclosed. In some embodiments, the peroxidase-activatable aryl moiety is tyramine or a tyramine derivative. Embodiments of methods for making and using the hapten conjugates also are disclosed. In particular embodiments, the hapten conjugates are used in a signal amplification assay. In certain embodiments, the hapten is an oxazole, a pyrazole, a thiazole, a benzofurazan, a triterpene, a urea, a thiourea other than a rhodamine thiourea, a nitroaryl other than dinitrophenyl or trinitrophenyl, a rotenoid, a cyclolignan, a heterobiaryl, an azoaryl, a benzodiazepine, or 7-diethylamino-3-carboxycoumarin. The hapten is coupled to the peroxidase-activatable aryl moiety directly or indirectly via a linker. In certain embodiments, the hapten conjugates are used in multiplexed assays. 1. A hapten conjugate , comprising:a hapten selected from an oxazole, a pyrazole, a thiazole, a benzofurazan, a triterpene, a urea, a thiourea other than a rhodamine thiourea, a nitroaryl other than dinitrophenyl or trinitrophenyl, a rotenoid, a cyclolignan, a heterobiaryl, an azoaryl, a benzodiazepine, 2,3,6,7-tetrahydro-11-oxo-1H,5H,11H-[1]benzopyrano[6,7,8-ij]quinolizine-10-carboxylic acid, or 7-diethylamino-3-carboxycoumarin;a linker; anda tyramine or a tyramine derivative.2. (canceled)6. (canceled)811.-. (canceled)1332.-. (canceled)33. A method , comprising:(a) immobilizing a first peroxidase on a first target in a sample, wherein the first peroxidase is capable of reacting with a peroxidase-activatable aryl moiety;(b) contacting the sample with a solution comprising a first hapten conjugate, the first hapten conjugate comprising a first hapten selected from an oxazole, a pyrazole, a thiazole, a benzofurazan, a triterpene, a urea, a thiourea other than a rhodamine thiourea, a nitroaryl other than dinitrophenyl or trinitrophenyl, a rotenoid, a cyclolignan, a heterobiaryl, an ...

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Номер записи: 7
18-07-2013 дата публикации

Labeling Agent and Methods for Simultaneous Sequencing and Quantification of Multiple Peptides and Proteins Using the Same

Номер: US20130183704A1
Автор: JUNG Yong Sik, Lee Hee Yoon, Seo Jong Cheol, Shin Seung Koo, Suh Min Soo, Yoon Hye Joo
Принадлежит: POSTECH ACADEMY-INDUSTRY FOUNDATION

The present invention provides a compound that can utilize hydrogen isotope and, at the same time, can quantify multiplexed samples at one time, as well as decreasing the cost for synthesis of the labeling agent. In addition, the present invention provides a novel method for quantitatively analyzing protein and peptide analytes having different quantities form each other using the labeling agent, wherein y-type fragment ions having a high mass which comprises the analyte remained after coupling the labeling agent with the analyte and then removing a part of the labeling agent through tandem mass spectrometry are utilized to conduct the quantitative analysis. 3. The compound according to claim 2 , characterized in that Ris octyl; and Ris heptyl.5. The compound according to claim 1 , characterized in that{'sub': 1', '2, 'Rand Rare'}{'sub': 3', '6', '4', '2', '3', '6', '4', '2', '2, 'CHC≡CCHCHand CDC≡CCHCDCH, respectively;'}{'sub': 3', '6', '4', '2', '3', '6', '4', '2', '2, 'CHC≡CCHCDand CDC≡CCHCHCH, respectively;'}{'sub': 3', '6', '4', '2', '3', '6', '4', '2', '2, 'CDC≡CCHCHand CHC≡CCHCDCH, respectively; or'}{'sub': 3', '6', '4', '2', '3', '6', '4', '2', '2, 'CDC≡CCHCDand CHC≡CCHCHCH, respectively.'}6. The compound according to claim 1 , characterized in that Ris a side chain of any one amino acid residue selected from the group consisting of glycine claim 1 , alanine claim 1 , serine claim 1 , valine claim 1 , leucine claim 1 , isoleucine claim 1 , methionine claim 1 , glutamine claim 1 , asparagine claim 1 , cysteine claim 1 , histidine claim 1 , phenylalanine claim 1 , arginine claim 1 , tyrosine and tryptophan.7. The compound according to claim 1 , characterized in that Ris hydroxy claim 1 , succinimid-N-oxy claim 1 , 3-sulfosuccinimid-N-oxy claim 1 , benzotriazol-1-yl-oxy claim 1 , pentahalobenzyloxy claim 1 , 4-nitrophenoxy or 2-nitrophenoxy.8. The compound according to claim 1 , characterized in that said compound is any one selected from the group consisting ...

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Номер записи: 8
05-09-2013 дата публикации

Novel Intermediate for Preparing Tapentadol or Analogues Thereof

Номер: US20130231478A1
Автор: LI DEGANG, LI XIAOXIANG, XU ZIAO, ZHAO YUANHAI
Принадлежит:

The invention discloses a novel intermediate for preparing tapentadol and analogues thereof, wherein the structural formula is shown as formula I or II, and the groups are defined as the specification. The invention further discloses a method for preparing the novel intermediate and use of the intermediate for preparing tapentadol and analogues thereof. The invention can remarkably improve the product yield and quality of tapentadol, reduce the production cost, and simplify the production procedure. The preparation process is environment friendly, thus more suitable for the requirements of industrial production. 2. The compound according to claim 1 , wherein Ris selected from Cl claim 1 , methyl claim 1 , OH claim 1 , NHor methoxy.3. The compound according to claim 1 , characterized in that Y is selected from OR claim 1 , wherein Ris selected from methyl claim 1 , ethyl claim 1 , n-propyl or isopropyl.4. The compound according to claim 1 , characterized in that Y is selected from NRR claim 1 , wherein R claim 1 , Rand N form substituted or unsubstituted saturated nitrogen-containing heteorcyclyl containing oxygen or not jointly.5. The compound according to claim 4 , wherein R claim 4 , Rand N form tetrahydropyrrole ring claim 4 , piperidine ring claim 4 , 4-methylpiperidine ring claim 4 , morpholine ring claim 4 , methylpiperazine ring or 4-hydroxypiperidine jointly.6. The compound according to claim 1 , selected from the following compounds:valeryl 2-methyl-3-(3-methoxyphenyl)chloride;methyl 2-methyl-3-(3-methoxyphenyl)sulfovalerate;methyl 2-methyl-3-(3-hydroxyphenyl) ulfovalerate;2-methyl-3-(3-hydroxyphenyl)sulfovaleramide;N,N-dimethyl-2-methyl-3-(3-methoxyphenyl)sulfovaleramide;N,N-dimethyl-2-methyl-3-(3-hydroxyphenyl)sulfovaleramide;N,N-diethyl-2-methyl-3-(3-methoxyphenyl)valeramide;3-(3-methoxyphenyl)-2-methyl-1-(piperidin-1-yl)pentan-1-one;3-(3-methoxyphenyl)-2-methyl-1-(4-methylpiperidin-1-yl)pentan-1-one;3-(3-methoxyphenyl)-2-methyl-1-(morpholin-1-yl)pentan- ...

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Номер записи: 9
19-09-2013 дата публикации

Calcium-sensing receptor-active compounds

Номер: US20130244995A1
Автор: Lars Kristian Albert Blæhr, Per VEDSØ
Принадлежит: Leo Pharma AS

Compounds of general formula (I), their use as calcium receptor-active compounds for the prophylaxis, treatment or amelioration of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism, pharmaceutical compositions comprising said compounds, and methods of treating diseases with said compounds.

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Номер записи: 10
26-09-2013 дата публикации

SEPARATING AGENT FOR PROTEIN PURIFICATION AND PROTEIN PURIFICATION METHOD

Номер: US20130253142A1
Автор: KOMIYA Katsuo, MASUMOTO Seiji, Nakamura Koji
Принадлежит: TOSOH CORPORATION

A novel separating agent for protein purification which not only can adsorb proteins in a sufficient amount for protein purification from a low concentration buffer but also can desorb the adsorbed protein easily just by altering the pH of the buffer and a simple and economical method for its production and a method for protein purification using it. 4. The separating agent for protein purification according to claim 1 , wherein the amount of the ligand on the support is at least 100 μmol/ml-support.5. The separating agent for protein purification according to claim 1 , wherein the support is made of a crosslinked polymer.9. The method for producing the separating agent for protein purification according to claim 6 , wherein the activator is carbonyldiimidazole.10. A method for protein purification claim 1 , which comprises dissolving a protein to be purified in a first buffer claim 1 , contacting the resulting protein solution with the separating agent for protein purification as defined in to allow the separating agent to adsorb the protein and then passing a second buffer having a different pH from the first buffer through the separating agent to elute the protein adsorbed on the separating agent. The present invention relates to a novel separating agent having a specific ligand for protein purification, a process for producing it and a protein purification method using it.In recent years, several techniques have been developed and/or optimized to effect separation and purification of target compounds from an aqueous mixture. Such separation and/purification techniques include, for example, ion exchange chromatography, hydrophobic interaction chromatography (HIC) (for example, Non-Patent Document 1), affinity chromatography and the like. The multiplicity of such chromatographic techniques reflects the difficulty in effecting separation and/or purification of target compounds while minimizing the complexity of the separation and/or purification procedure. Each of ...

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Номер записи: 11
31-10-2013 дата публикации

Substituted 2-[2-(phenyl) ethylamino] alkaneamide derivatives and their use as sodium and/or calcium channel modulators

Номер: US20130289122A1
Автор: Alessandra Restivo, Cibele Sabido-David, Elena Colombo, Emanuela Izzo, Piero Melloni, Simona Francisconi
Принадлежит: Newron Pharmaceuticals SpA

Substituted 2-[2-(phenyl)ethylamino]alkaneamide derivatives, pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing them are useful as sodium and/or calcium channel modulators for preventing, alleviating and curing pathologies wherein the above mechanisms play a pathological role. The compounds may be particularly useful for the prevention, alleviation, and curing of, for example, neurological, cognitive, psychiatric, inflammatory, urogenital and gastrointestinal diseases.

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Номер записи: 12
14-11-2013 дата публикации

CYCLOPROPYLAMINE DERIVATIVES USEFUL AS LSD1 INHIBITORS

Номер: US20130303545A1
Автор: Buesa Arjol Carlos, Maes Tamara
Принадлежит:

The invention relates to methods and compositions for the treatment or prevention of protein conformation disorders. In particular, the invention relates to an LSD1 inhibitor for use in treating or preventing a protein conformation disorder, such as, e.g., Huntington Disease. 121-. (canceled)22. A method of treating or preventing a cognitive symptom in an individual having a protein conformation disorder comprising identifying an individual in need of such treatment and administering to said individual for a sufficient period of time an amount of an LSD1 inhibitor sufficient to improve the cognitive symptom or reduce the rate of decline of the cognitive symptom thereby treating or preventing said cognitive symptom.23. The method of claim 22 , wherein said protein conformation disorder is a CAG expansion disorder claim 22 , Alzheimer Disease or Parkinson Disease.2427-. (canceled)28. The method of claim 23 , wherein said CAG expansion disorder is Huntington disease claim 23 , Kennedy Disease claim 23 , Spinocerebellar Ataxia 1 claim 23 , Spinocerebellar Ataxia 2 claim 23 , Spinocerebellar Ataxia 3 claim 23 , Spinocerebellar Ataxia 6 claim 23 , Spinocerebellar Ataxia 7 claim 23 , or Spinocerebellar Ataxia 17.29. A method of treating or preventing a motor symptom in an individual having a protein conformation disorder comprising identifying an individual in need of such treatment and administering to said individual for a sufficient period of time an amount of an LSD1 inhibitor sufficient to reduce the rate of decline in said motor symptom thereby treating or preventing said motor symptom.30. The method of claim 29 , wherein said protein conformation disorder is a CAG expansion disorder claim 29 , Alzheimer Disease claim 29 , or Parkinson Disease.3135-. (canceled)36. A method of increasing longevity in an individual having a protein conformation disorder comprising identifying an individual in need of such treatment and administering to said individual for a sufficient ...

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Номер записи: 13
14-11-2013 дата публикации

Enzyme inhibitors

Номер: US20130303576A1
Автор: Alastair David Graham Donald, Andrew James Belfield, Carl Leslie North, David Festus Charles Moffat, Stewart Andrew Wayne Jones
Принадлежит: Chroma Therapeutics Ltd

Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent ═CH— or ═N—; W is —CH═CH—Or —CH 2 CH 2 —; R 1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; R2 and R3 are selected from the side chains of a natural or non-natural alpha amino acid, provided that neither R 2 nor R 3 is hydrogen, or R 2 and R 3 , taken together with the carbon to which they are attached, form a 3-6 membered saturated cycloalkyl or heterocyclyl ring; Y is a bond, —C(═O)—, —S(═O) 2 —, —C(═O)O—, —C(═O)NR′—, —C(═S)—NR′, —C(═NH)NR′ or —S(═O) 2 NR— wherein R′ is hydrogen or optionally substituted C 1 -C 6 alkyl; L 1 is a divalent radical of formula -(Alk 1 ) m (Q) n (Alk 2 ) p - wherein m, n, p, Q. Alk 1 and Alk 2 are as defined in the claims; X 1 represents a bond; —C(═O); or —S(═O) 2 —; —NR 4 C(═O)—, —C(═O)NR 4 —, —NR 4 C(═O)NR 5 —, —NR 4 S(═O) 2 —, or —S(═O) 2 NR 4 — wherein R 4 and R 5 are independently hydrogen or optionally substituted C 1 -C 6 alkyl; and z is 0 or 1.

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Номер записи: 14
28-11-2013 дата публикации

COMPOUND, KINESIN SPINDLE PROTEIN INHIBITOR, AND APPLICATION THEREOF

Номер: US20130317110A1
Автор: Kamiya Nozomu, Sugiyama Hajime, Tomonaga Atsushi
Принадлежит: FUJITSU LIMITED

A compound represented by the following General Formula (I): 3. The compound according to claim 1 ,{'sub': 1', '2', '1', '2, 'wherein in the compound represented by General Formula (I), Ror Ris or both Rand Rare an ethyl group or a methyl group, and X represents a hydrogen atom, a fluorine atom or a chlorine atom.'}7. The pharmaceutical composition according to claim 6 ,wherein the disorder mediated at least partially by the kinesin spindle protein is a cell proliferative disease.8. The pharmaceutical composition according to claim 6 ,wherein the disorder mediated at least partially by the kinesin spindle protein is a cell proliferative disease, andwherein the cell proliferative disease is a cancerous disease.9. The pharmaceutical composition according to claim 6 ,wherein the disorder mediated at least partially by the kinesin spindle protein is a cell proliferative disease,wherein the cell proliferative disease is a cancerous disease, andwherein the cancerous disease is lung cancer, bronchial cancer, prostate cancer, breast cancer, pancreas cancer, colon cancer, rectal cancer, small intestinal cancer, thyroid cancer, esophageal cancer, oral cancer, pharyngeal cancer, larynx cancer, stomach cancer, liver cancer, intrahepatic bile duct cancer, kidney cancer, renal pelvis cancer, bladder cancer, uterine corpus cancer, uterocervical cancer, ovary cancer, conjunctival cancer, lacrimal cancer, palpebral cancer, multiple myeloma, brain tumor, non-Hodgkin's lymphoma, melanoma, trophoblastic colon adenoma, acute myelocytic leukemia, chronic myelocytic leukemia, lymphatic leukemia, myelocytic leukemia, or any combination thereof.10. The pharmaceutical composition according to claim 6 , further comprising a pharmacologically acceptable carrier.11. The pharmaceutical composition according to claim 6 , further comprising at least one drug used for prevention or treatment of cancer.13. The method according to claim 12 ,wherein the cells are cells in vivo or cultured cells.14. ...

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Номер записи: 15
05-12-2013 дата публикации

COPOLYMERIZABLE METHINE AND ANTHRAQUINONE COMPOUNDS AND ARTICLES CONTAINING THEM

Номер: US20130324717A1
Автор: Fleischer Jean Carroll, King Gregory Allan, Pearson Jason Clay, Weaver Max Allen
Принадлежит:

This invention relates to polymerizable ultraviolet light absorbers and yellow colorants and their use in ophthalmic lenses. In particular, this invention relates to polymerizable ultraviolet light absorbing methane compounds and yellow compounds of the methine and anthraquinone classes that block ultraviolet light and/or violet-blue light transmission through ophthalmic lenses. 2. The compound of claim 1 , wherein:{'sub': 1', '1', '12', '1', '12', '3', '8', '3', '8', 'n', '1', '6', '1', '12', '1', '12', '1, 'R and Rare independently selected from C-C-alkyl, substituted C-C-alkyl, aryl, heteroaryl, C-C-cycloalkyl, C-C-alkenyl, —(CHR′CHR″O—)—, C-C-alkylsulfonyl, arylsulfonyl, C-C-acyl, substituted-C-C-acyl, -L-Q and -Q; or R and Rare combined to make phthalimido, succinimido, morpholino, thiomorpholino, pyrrolidino, piperidino, piperazino, or thiomorpholino-S,S-dioxide;'}{'sub': '2', 'Ris hydrogen;'}{'sub': '1', 'Xis cyano;'}{'sub': '2', 'Xis —COY;'}{'sub': '2', 'Y is selected from —NR′-L-Q, —N-(L-Q);'}R′ is hydrogen;{'sub': 2', '2', '2', '3, 'L is selected from —CHCH—O—, —CHCH(CH)—O—;'}n is an integer selected from 1 to 3; and{'sub': 6', '7', '6', '7, 'Q is —C(O)C(R)═CHR, wherein Ris methyl and Ris hydrogen.'}4. The compound of claim 1 , wherein:{'sub': 1', '2', '2', '2', '2', '3', '2', '3', '3', '1, 'R and Rare independently selected from methyl, ethyl, —CHCHCN, —CHCHOCOCH; —CHCH(CH)OCOCH; or R and Rare combined to make thiomorpholino-S,S-dioxide;'}{'sub': '2', 'Ris hydrogen;'}{'sub': '1', 'Xis cyano;'}{'sub': '2', 'Xis —COY;'}{'sub': '2', 'Y is selected from —NR′-L-Q, and —N-(L-Q);'}R′ is hydrogen;{'sub': 2', '2', '2', '3, 'L is selected from —CHCH—O—, and —CHCH(CH)—O—; and'}{'sub': 6', '7', '6', '7, 'Q is —C(O)C(R)═CHR, wherein Ris methyl and Ris hydrogen.'}5. The compound of claim 1 , wherein:{'sub': '1', 'R and Rcombined to make thiomorpholino-S,S-dioxide;'}{'sub': '2', 'Ris hydrogen;'}{'sub': '1', 'Xis cyano;'}{'sub': '2', 'Xis —COY;'}Y is —NR′-L-Q;R′ is ...

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Номер записи: 16
20-03-2014 дата публикации

Inhibitors of Histone Deacetylase

Номер: US20140080800A1
Автор: Haggarty Stephen, Holson Edward, Tsai Li-Huei, Wagner Florence Fevrier, Weiwer Michel, ZHANG YAN-LING
Принадлежит:

The present invention relates to compounds of formula (I): 5. The compound of or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , or prodrug thereof claim 4 , wherein Ris selected from phenyl claim 4 , 2-pyridinyl claim 4 , 3-pyridinyl claim 4 , 4-pyridinyl claim 4 , 2-pyrimidinyl claim 4 , 4-pyrimidinyl claim 4 , 5-pyrimidinyl claim 4 , 2-pyrazinyl claim 4 , oxazolyl claim 4 , thiazolyl claim 4 , and isoxazolyl.12. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.13. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition wherein said condition is associated with histone deacetylase activity in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.14. The method of claim 13 , wherein the condition is selected from a neurological disorder claim 13 , memory loss or impairment claim 13 , cognitive function disorder or impairment claim 13 , extinction learning disorder claim 13 , fungal disease or infection claim 13 , inflammatory disease claim 13 , hematological disease claim 13 , and neoplastic disease.15. The method of claim 14 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress ...

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Номер записи: 17
20-03-2014 дата публикации

Method of treating estrogen receptor (er) -positive breast cancers with selective androgen receptor modulator (sarms)

Номер: US20140080905A1
Автор: James T. Dalton, Mitchell S. Steiner, Ramesh Narayanan, Sunjoo Ahn
Принадлежит: GTx Inc

This invention relates to the treatment of androgen receptor-positive breast cancer in a subject, for example a female subject. Accordingly, this invention provides methods of: a) treating a subject suffering from breast cancer; b) treating a subject suffering from metastatic breast cancer; c) treating a subject suffering from refractory breast cancer; d) treating a subject suffering from AR-positive breast cancer; e) treating a subject suffering from AR-positive refractory breast cancer; f) treating a subject suffering from AR-positive metastatic breast cancer; g) treating a subject suffering from AR-positive and ER-positive breast cancer; h) treating a subject suffering from triple negative breast cancer; i) treating a subject suffering from advanced breast cancer; j) treating a subject suffering from breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and/or fulvestrant treatments; k) treating, preventing, suppressing or inhibiting metastasis in a subject suffering from breast cancer; l) prolonging survival of a subject with breast cancer, and/or m) prolonging the progression-free survival of a subject with breast cancer; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound, comprising administering to the subject a therapeutically effective amount of a SARM compound of this invention.

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Номер записи: 18
07-01-2016 дата публикации

NEOSEPTINS: SMALL MOLECULE ADJUVANTS

Номер: US20160000907A1
Автор: Beutler Bruce, Boger Dale L.
Принадлежит:

A MD-2:TLR4 complex agonist compound is disclosed whose structure corresponds to Formula (I), as defined within. Also disclosed are a method of its preparation and use, as well as a pharmaceutical composition containing the same. 21. The compound according to claim 1 , P wherein X is absent or O.3. The compound according to claim 1 , wherein Y is CH.4. The compound according to claim 1 , wherein ring structure W contains up to 10 atoms in the ring structure.5. The compound according to claim 1 , wherein W is a single ring structure.7. The compound according to claim 6 , wherein no more than two of A claim 6 , B claim 6 , E claim 6 , G claim 6 , L and M are nitrogen.8. The compound according to claim 6 , wherein X is absent or O.9. The compound according to claim 6 , wherein Ris a bulky hydrocarbyl group containing 4-6 carbon atoms.10. The compound according to claim 6 , wherein ring structure W contains a substituent selected from the group consisting of azido claim 6 , fluoro claim 6 , methyl claim 6 , methoxy and trifluoromethyl groups claim 6 , and said substituent is present at 4-position of a 6-membered ring and the 3-position of a 5-membered ring counting from the position of attachment to the remainder of the molecule.12. The compound according to claim 11 , wherein Ris a tert-butyl group claim 11 , a neopentyl group claim 11 , a cyclopentyl group or cyclohexyl group.13. The compound according to claim 11 , wherein ring structure W is phenyl.16. A pharmaceutical composition that comprises an effective amount of a compound of or a pharmaceutically acceptable salt thereof dissolved or dispersed in a physiologically acceptable carrier.17. The pharmaceutical composition according to wherein said effective amount is an adjuvant effective amount.18. The pharmaceutical composition according to wherein said effective amount is a TLR4 agonist effective amount.19. An improved method of vaccination wherein mammalian cells in need of vaccination are contacted with an ...

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Номер записи: 19
02-01-2020 дата публикации

DUAL MECHANISM INHIBITORS FOR THE TREATMENT OF DISEASE

Номер: US20200002324A1
Автор: deLong Mitchell A., Royalty Susan M., Sturdivant Jill Marie
Принадлежит:

Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved. 121-. (canceled)23. A composition claim 22 , comprising the compound of .24. A pharmaceutical composition claim 22 , comprising the compound of and a pharmaceutically acceptable carrier.25. The pharmaceutical composition of claim 24 , wherein the pharmaceutically acceptable carrier is saline buffered to a pH of about 5.5 to about 6.5.26. A method of treating an eye disease in a subject in need thereof claim 22 , comprising administering to the subject an effective amount of the compound of .27. The method of claim 26 , wherein the eye disease comprises glaucoma.28. The method of claim 26 , wherein the eye disease comprises wet age-related macular degeneration claim 26 , dry age-related macular degeneration claim 26 , or diabetic macular edema.29. The method of claim 26 , wherein the eye disease comprises dry eye.30. The method of claim 26 , wherein the eye disease comprises ocular hypertension.31. The method of claim 26 , wherein the administration is topical administration to an eye of the subject.32. A method of treating an eye disease in a subject in need thereof claim 23 , comprising administering to the subject an effective amount of the composition of .33. The method of claim 32 , wherein the eye disease comprises glaucoma.34. The method of claim 32 , wherein the eye disease comprises wet age-related macular degeneration claim 32 , dry age-related macular degeneration claim 32 , or diabetic macular edema.35. The method of claim 32 , wherein the eye disease comprises dry eye.36. ...

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Номер записи: 20
08-01-2015 дата публикации

DUAL-ACTING ANTIHYPERTENSIVE AGENTS

Номер: US20150011597A1
Автор: Hegde Sharath, Marquess Daniel
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC.

The invention is directed to compounds of formula I: 136-. (canceled)37. A method for treating hypertension , comprising administering to a patient a therapeutically effective amount of a compound having both ATreceptor-antagonizing activity and neprilysin enzyme-inhibiting activity.38. The method of claim 37 , wherein the compound has a pKvalue for binding to an ATreceptor greater than or equal to about 5.0 and a pICvalue for the inhibition of the neprilysin enzyme greater than or equal to about 5.0.39. The method of claim 38 , wherein the compound has a pKvalue greater than or equal to about 6.0.40. The method of claim 39 , wherein the compound has a pKvalue within the range of about 8.0-10.0.41. The method of claim 38 , wherein the compound has a pICvalue greater than or equal to about 6.0.42. The method of claim 41 , wherein the compound has a pICvalue within the range of about 7.0-10.0.43. (canceled)44. A method for treating heart failure claim 41 , comprising administering to a patient a therapeutically effective amount of a compound having both ATreceptor-antagonizing activity and NEP enzyme-inhibiting activity.45. The method of claim 44 , wherein the compound has a pKvalue for binding to an ATreceptor greater than or equal to about 5.0 and a pICvalue for the inhibition of the neprilysin enzyme greater than or equal to about 5.0.46. (canceled)47. A method of treating a patient suffering from a disease or disorder that is treated by antagonizing the ATreceptor and/or inhibiting the NEP enzyme claim 44 , comprising administering to a patient a therapeutically effective amount of a compound having both ATreceptor-antagonizing activity and NEP enzyme-inhibiting activity.48. The method of claim 47 , wherein the compound has a pKvalue for binding to an ATreceptor greater than or equal to about 5.0 and a pICvalue for the inhibition of the neprilysin enzyme greater than or equal to about 5.0.4954-. (canceled) This application claims the benefit of U.S. Provisional ...

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Номер записи: 21
21-01-2016 дата публикации

HETEROCYCLIC INHIBITORS OF THE SODIUM CHANNEL

Номер: US20160016939A1
Автор: Holland Richard, Lamontagne Jason, PAJOUHESH Hassan, Pajouhesh Hossein, Whelan Brendan, ZHANG Lingyun
Принадлежит:

The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention concerns heterocyclic compounds (e.g., compounds according to any of Formulas (I)-(X) or Compounds (1)-(92) of Table 1) that are that are useful in treatment of conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotrophic lateral sclerosis, glaucoma, ischemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome.

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Номер записи: 22
18-01-2018 дата публикации

INHIBITORS OF HISTONE DEACETYLASE

Номер: US20180016282A9
Автор: Haggarty Stephen J., Holson Edward, Tsai Li-Huei, Wagner Florence Fevrier, Weiwer Michel, ZHANG YAN-LING
Принадлежит:

The present invention relates to compounds of formula (I): 5. The compound of or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , or prodrug thereof claim 4 , wherein Ris selected from phenyl claim 4 , 2-pyridinyl claim 4 , 3-pyridinyl claim 4 , 4-pyridinyl claim 4 , 2-pyrimidinyl claim 4 , 4-pyrimidinyl claim 4 , 5-pyrimidinyl claim 4 , 2-pyrazinyl claim 4 , oxazolyl claim 4 , thiazolyl claim 4 , and isoxazolyl.12. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.13. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition wherein said condition is associated with histone deacetylase activity in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.14. The method of claim 13 , wherein the condition is selected from a neurological disorder claim 13 , memory loss or impairment claim 13 , cognitive function disorder or impairment claim 13 , extinction learning disorder claim 13 , fungal disease or infection claim 13 , inflammatory disease claim 13 , hematological disease claim 13 , and neoplastic disease.15. The method of claim 14 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress ...

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Номер записи: 23
25-01-2018 дата публикации

SYNTHESIS OF POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS

Номер: US20180022757A1
Автор: Chiu Anna, Enquist, Griggs Nolan, Hale Christopher, Herpt Jochem Van, Ikemoto Norihiro, JR. John, Keaton Katie Ann, Kraft Matt, Lazerwith Scott E., Leeman Michel, Peng Zhihui, Schrier Kate, Trinidad Jonathan, Waltman Andrew W.
Принадлежит:

Methods of making compounds of Formula I are disclosed: 1123-. (canceled)125. The process of wherein B-1 is reacted with J-1 in the presence of an acid selected from the group consisting of an inorganic acid claim 124 , an organic acid claim 124 , a halogenated organic acid claim 124 , and mixtures thereof.126. The process of wherein the acid is selected from the group consisting of hydrochloric acid claim 125 , hydrobromic acid claim 125 , hydroiodic acid claim 125 , trifluoromethanesulfonic acid claim 125 , formic acid claim 125 , trifluoroacetic acid claim 125 , trichloroacetic acid claim 125 , perfluoropropionic acid claim 125 , and a mixture thereof.127. The process of wherein the acid is trifluoroacetic acid.128. The process of any one of to claim 126 , wherein J-1 is in the form of a salt or co-crystal.129. The process of any one of to wherein Hal is F.133145-. (canceled)147152-. (canceled)154193-. (canceled)195. The process of wherein the acid is selected from the group consisting of an inorganic acid claim 194 , an organic acid claim 194 , a halogenated organic acid claim 194 , a Lewis acid and mixtures thereof.196. The process of any one of to wherein the acid is selected from the group consisting of hydrochloric acid claim 194 , hydrobromic acid claim 194 , hydroiodic acid claim 194 , trifluoromethanesulfonic acid claim 194 , formic acid claim 194 , trifluoroacetic acid claim 194 , trichloroacetic acid claim 194 , perfluoropropionic acid claim 194 , dichloroacetic acid claim 194 , chloroacetic acid claim 194 , acetic acid claim 194 , para-toluenesulfonic acid claim 194 , methane sulfonic acid claim 194 , zinc chloride claim 194 , magnesium bromide claim 194 , magnesium triflate claim 194 , copper triflate claim 194 , scandium triflate claim 194 , and a mixture thereof.197. The process of any one of to wherein the acid is trifluoroacetic acid.198242-. (canceled) This application claims priority to and the benefit of U.S. Provisional Application No. 62/015, ...

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Номер записи: 24
28-01-2021 дата публикации

SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF

Номер: US20210024458A1
Автор: COSS Christopher C., Dalton James T., DUKE Charles B., Hwang Dong-Jin, JONES Amanda, Miller Duane D., NARAYANAN Ramesh, PONNUSAMY Thamarai
Принадлежит:

This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other 5 hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject. 3. The method according to claim 1 , wherein Qis CN.4. The method according to claim 1 , wherein Qand Qare joined together to form a substituted or unsubstituted C-Cnon-aromatic carbocyclic or a substituted or unsubstituted C-Cheterocyclic ring.6. The method according to claim 1 , wherein said disease or condition is hypergonadism claim 1 , hypersexuality claim 1 , sexual dysfunction claim 1 , gynecomastia claim 1 , precocious puberty in a male claim 1 , hair loss claim 1 , hyperandrogenic dermatological disorders claim 1 , pre-cancerous lesions of the prostate claim 1 , benign prostate hyperplasia claim 1 , prostate cancer and/or other androgen-dependent cancers.8. The method according to claim 7 , wherein said disease or condition is hypergonadism claim 7 , hypersexuality claim 7 , sexual dysfunction claim 7 , gynecomastia claim 7 , precocious puberty in a male claim 7 , hair loss claim 7 , hyperandrogenic dermatological disorders claim 7 , pre-cancerous lesions of the prostate claim 7 , benign prostate hyperplasia claim 7 , prostate cancer and/or other androgen-dependent cancers. This Application is a Continuation application of U.S. patent application Ser. No. 16/153,193, filed on Oct. 5, 2018, which is a Continuation-in-Part application of U.S. patent application Ser. No. 15/830,688, filed on Dec. 4, 2017, which is a Continuation-in-Part application of U.S. ...

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Номер записи: 25
04-02-2016 дата публикации

CURCUMIN ANALOGUES AS ZINC CHELATORS AND THEIR USES

Номер: US20160031795A1
Автор: Golub Lorne, Johnson Francis
Принадлежит:

This invention provides a compound having the structure 2. The compound of claim 1 , wherein when Ris H claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , or R claim 1 , is —NO claim 1 , —NRR claim 1 , —NHRR claim 1 , —SOR claim 1 , —COR claim 1 , CF claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl; or a salt thereof.3. The compound of claim 1 , wherein when Ris H claim 1 , Ror Ris —NO claim 1 , —NRR claim 1 , —NHRR; or a salt thereof.4. The compound of claim 1 , wherein when Ris H claim 1 , Ror Ris —NRRor —NHRR; or a salt thereof.5. The compound of claim 1 , wherein{'sub': 1', '14, 'claim-text': {'sub': '14', 'wherein Ris methoxy or —NH-phenyl;'}, 'Ris H or —COR,'}{'sub': 2', '5', '6', '7', '10', '11, 'R, R, R, R, Rand Rare each H;'}{'sub': 3', '4', '8', '9', '3', '3', '2', '3', '2, 'sup': '+', 'R, R, R, and Rare each, independently H, —OH, —OCH, —N(CH)or —NR(CH);'}or a salt thereof.11. The compound of wherein Ris methoxy claim 8 , —ORor —NRR claim 8 ,{'sub': 15', '3-10', '2-10', '2-10, 'wherein Ris H, Calkyl, Calkenyl, or Calkynyl;'}{'sub': 16', '17', '1-10', '2-10', '2-10, 'Rand Rare each, independently, H, Calkyl, Calkenyl, Calkynyl, aryl, heteroaryl, or heterocyclyl;'}or a salt thereof.12. The compound of wherein Ris methoxy or —NRR claim 11 ,{'sub': 16', '17', '1-10', '2-10', '2-10, 'wherein Rand Rare each, independently, H, Calkyl, Calkenyl, Calkynyl, aryl, heteroaryl, or heterocyclyl;'}or a salt thereof.13. The compound of wherein Ris —OR claim 11 , wherein Ris H claim 11 , Calkyl claim 11 , Calkenyl claim 11 , or Calkynyl; or a salt thereof.14. The compound of claim 12 , wherein{'sub': 14', '16', '17, 'claim-text': {'sub': 16', '17, 'wherein Rand Rare each, independently, H or aryl;'}, 'Ris —NRR,'}{'sub': 2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '28', '29', '29, 'claim-text': [{'sub': 28', '29', '1-10, 'wherein Rand Rare each, H or Calkyl;'}, 'or a salt thereof., 'R, R, R, R, R, R, R, R, R, and Rare each independently, H, ...

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Номер записи: 26
04-02-2016 дата публикации

Bisphenol polymer precursor replacements

Номер: US20160032043A1
Автор: Horst A. von Recum
Принадлежит: CASE WESTERN RESERVE UNIVERSITY

Use of biologically-derived polyphenols for the preparation of epoxy resins is described. Examples of biologically-derived polyphenols include resveratrol, genistein, daidzein, and polyphenols synthesized from tyrosine. Because the epoxy resins are prepared from biologically-derived materials, they provide epoxy resins that will degrade into biologically harmless materials. The epoxy resins can be used to provide coating compositions.

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Номер записи: 27
17-02-2022 дата публикации

PHENYLPIPERAZINE PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) MODULATORS AND THEIR USE

Номер: US20220047582A1
Автор: Barta Thomas E., Bourne Jonathan William, Bowers Simeon, Monroe Kyle D., Muehlemann Michael M., Pandey Anjali
Принадлежит:

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels. 112.-. (canceled)14. The method of claim 13 , wherein an uptake of LDL by hepatocytes in the subject is modulated.15. The method of claim 13 , wherein said metabolic disease is diabetes.16. The method of claim 13 , wherein the compound of formula I is formulated as a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient.17. The method of claim 16 , wherein said pharmaceutical composition further comprises a second pharmaceutical drug compound.18. The method of claim 17 , wherein said second pharmaceutical drug compound is selected from the group consisting of a statin claim 17 , a cardiovascular drug claim 17 , a metabolic drug claim 17 , and an antihypertensive drug.19. The method of claim 13 , wherein the compound is selected from the group consisting of:N-phenyl-4-(piperazin-1-yl)benzenesulfonamide;N-isopropyl-4-((4-(piperazin-1-yl)phenyl)sulfonamido)benzamide;N-methyl-4-((4-(piperazin-1-yl)phenyl)sulfonamido)benzamide;N-(3,4-dimethylphenyl)-4-(piperazin-1-yl)benzenesulfonamide;N-(3,5-dimethylphenyl)-4-(piperazin-1-yl)benzenesulfonamide;N-(3,5- ...

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Номер записи: 28
30-01-2020 дата публикации

INDENYL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND MEDICAL USES THEREOF

Номер: US20200031795A1
Автор: Boyd Michael R., Chen Xi, KEETON Adam B., Piazza Gary A.
Принадлежит: ADT PHARMACEUTICALS, LLC

Disclosed are compounds, for example, compounds of formula I, 137-. (canceled)39. The compound claim 38 , (Z)- or (E)-isomer thereof claim 38 , or a pharmaceutically acceptable salt thereof claim 38 , of claim 38 , wherein Ris a substituted or unsubstituted group selected from phosphonooxy claim 38 , phosphonoalkyloxy claim 38 , alkylcarbonyloxyalkyloxy claim 38 , aminocarbonyloxyalkyloxy claim 38 , arylcarbonyloxy claim 38 , arylalkylcarbonyloxy claim 38 , aryloxycarbonyloxy claim 38 , heterocyclylcarbonyloxy and heterocyclylalkylcarbonyloxy.40. The compound claim 39 , (Z)- or (E)-isomer thereof claim 39 , or a pharmaceutically acceptable salt thereof claim 39 , of claim 39 , wherein Ris a substituted or unsubstituted group selected from phosphonooxy claim 39 , phosphonoalkyloxy claim 39 , arylcarbonyloxy claim 39 , arylalkylcarbonyloxy claim 39 , aryloxycarbonyloxy claim 39 , heterocyclylcarbonyloxy and heterocyclylalkylcarbonyloxy.41. The compound claim 40 , (Z)- or (E)-isomer thereof claim 40 , or a pharmaceutically acceptable salt thereof claim 40 , of claim 40 , wherein Ris a substituted or unsubstituted group selected from phosphonooxy claim 40 , phosphonoalkyloxy claim 40 , arylcarbonyloxy claim 40 , arylalkylcarbonyloxy and aryloxycarbonyloxy.42. The compound claim 38 , (Z)- or (E)-isomer thereof claim 38 , or a pharmaceutically acceptable salt thereof claim 38 , of claim 38 , wherein R′ is furanylalkyl optionally substituted with one or more of halo claim 38 , alkyl claim 38 , haloalkyl or alkoxy.43. The compound claim 42 , (Z)- or (E)-isomer thereof claim 42 , or a pharmaceutically acceptable salt thereof claim 42 , of claim 42 , wherein the furanylalkyl.44. The compound claim 38 , (Z)- or (E)-isomer thereof claim 38 , or a pharmaceutically acceptable salt thereof claim 38 , of claim 38 , wherein R claim 38 , R claim 38 , Rand Rare independently selected from hydrogen claim 38 , halogen claim 38 , alkoxy claim 38 , alkyl claim 38 , and haloalkyl.45. The ...

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Номер записи: 29
08-02-2018 дата публикации

COMPOSITIONS FOR THE TREATMENT OF KIDNEY AND/OR LIVER DISEASE

Номер: US20180037539A1
Автор: Duggan Karen Annette
Принадлежит: VECTUS BIOSYSTEMS LIMITED

The present invention relates to novel compounds and their use in the prophylactic and/or therapeutic treatment of kidney and/or liver disease. 2. The compound according to claim 1 , wherein Q is independently selected from —CH claim 1 , —C(O)OH claim 1 , —F claim 1 , —NH claim 1 , —OH and —OCH.3. The compound according to claim 1 , wherein Rto Rare independently C or N.4. The compound according to claim 1 , wherein n is 0 claim 1 , 1 or 2.5. The compound according to claim 1 , wherein the Calkyl carboxylic acid is carboxylic acid.6. The compound according to claim 1 , wherein X is —OH.10. A pharmaceutical composition comprising the compound according to claim 1 , and a pharmaceutically acceptable excipient.11. A method for the prophylactic or therapeutic treatment of kidney and/or liver disease in a subject comprising administering to the subject a compound according to .12. The method according to claim 11 , wherein the treatment prevents claim 11 , reduces or slows the progression of kidney and/or liver fibrosis.13. The method according to claim 11 , wherein the treatment reduces established kidney and/or liver fibrosis.14. The method according to claim 11 , wherein the treatment prevents claim 11 , reduces or slows renal tubular cell death.15. The method according to wherein the treatment prevents claim 11 , reduces or slows accumulation of hepatic fat.16. The method according to wherein the treatment restores normal tissue architecture.17. (canceled)18. (canceled)19. (canceled)20. (canceled)21. (canceled)22. (canceled) The present invention relates to novel compounds and their use in the prophylactic and/or therapeutic treatment of kidney and/or liver disease.The invention has been developed primarily for the prophylactic and/or therapeutic treatment of kidney and/or liver disease and will be described hereinafter with reference to this application. However, it will be appreciated that the invention is not limited to this particular field of use.Any discussion ...

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Номер записи: 30
07-02-2019 дата публикации

SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF

Номер: US20190040000A1
Автор: COSS Christopher C., Dalton James T., DUKE Charles B., Hwang Dong-Jin, JONES Amanda, Miller Duane D., NARAYANAN Ramesh, PONNUSAMY Thamarai
Принадлежит:

This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other 5 hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject. 3. The method according to claim 1 , wherein Qis CN.4. The method according to claim 1 , wherein Qand Qare joined together to form a substituted or unsubstituted C-Cnon-aromatic carbocyclic or a substituted or unsubstituted C-Cheterocyclic ring.6. The method according to claim 1 , wherein said condition is hypergonadism claim 1 , hypersexuality claim 1 , sexual dysfunction claim 1 , gynecomastia claim 1 , precocious puberty in a male claim 1 , alterations in cognition and mood claim 1 , depression claim 1 , hair loss claim 1 , hyperandrogenic dermatological disorders claim 1 , pre-cancerous lesions of the prostate claim 1 , benign prostate hyperplasia claim 1 , prostate cancer and/or other androgen-dependent cancers.9. The method according to claim 7 , wherein Qis CN.10. The method according to claim 7 , wherein Qand Qare joined together to form a substituted or unsubstituted C-Cnon-aromatic carbocyclic or a substituted or unsubstituted C-Cheterocyclic ring.12. The method of claim 7 , wherein said castration-resistant prostate cancer is AR overexpressing castration-resistant prostate cancer claim 7 , F876L mutation expressing castration-resistant prostate cancer claim 7 , F876L_T877A double mutation expressing castration-resistant prostate cancer claim 7 , AR-V7 expressing castration-resistant prostate cancer claim 7 , d567ES expressing castration-resistant prostate ...

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Номер записи: 31
16-02-2017 дата публикации

ANTIBACTERIALS AND/OR MODULATORS OF BIOFILM FORMATION AND METHODS OF USING THE SAME

Номер: US20170044097A1
Автор: "ODonnell Martin J.", Samaritoni Jack Geno, Scott William L.
Принадлежит:

Amides substituted with aromatic groups were synthesized and some were purified to create enantiomer pure compounds. The compounds were tested to determine their ability to inhibit the growth of bacteria and the formation of biofilms created by bacteria. Some of these compounds were found to be effective antibacterials and to effectively inhibit the formation of biofilms. 2. The compound according to claim 1 , wherein:{'sup': '1', 'sub': 2', '2', '3, 'Ris benzyl substituted with 1 to 3 halogens, —NH, —NO, —CN, or —CF; and'}{'sup': '2', 'sub': '2', 'Ris —OH or —NH;'}or a pharmaceutically acceptable salt thereof, or a metabolite thereof.3. The compound according to claim 1 , wherein:{'sup': '1', 'sub': 2', '2', '3, 'Ris benzyl substituted with 1 to 3 halogens, —NH, —NO, —CN, or —CF;'}{'sup': 2', '3, 'Ris —NHR;'}{'sup': 3', '5, 'sub': 2', 'n, 'Ris —(CH)—R;'}{'sup': '5', 'sub': 3', '1', '6', '1', '6', '2', '2', '3, 'Ris —OH, —CF, morpholinyl, pyridinyl, or benzyl optionally substituted with 1 to 3 halogen, C-Calkyl, C-Calkoxy, —OH, —NH, —NO, —CN, or —CF; and'}n is 1, 2, 3, or 4;or a pharmaceutically acceptable salt thereof, or a metabolite thereof.7. A method for reducing the growth of bacteria claim 1 , comprising the steps of:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'treating bacteria with at least one compound selected from the compounds of .'}9. The method according to claim 7 , wherein the bacteria is gram-negative bacteria.10Pseudomonas aeruginosa.. The method according to claim 7 , wherein the bacteria is11. The method according to claim 7 , further comprising the step of:reducing biofilm formation of the bacteria.12. The method according to claim 7 , further comprising the step of:treating an area that has been infected by the bacteria.13. The method according to claim 12 , wherein the area comprises surfaces or hair of an animal claim 12 , a human claim 12 , or a plant.14. A method of treating bacterial infections claim 12 , comprising the steps of:{' ...

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Номер записи: 32
15-02-2018 дата публикации

METHOD OF TREATING OR PREVENTING RAS-MEDIATED DISEASES

Номер: US20180044314A1
Автор: Boyd Michael R., Chen Xi, KEETON Adam B., Piazza Gary A.
Принадлежит:

Disclosed are compounds, for example, a compound of formula I, wherein R, R, R-R, n, X, Y, Y′, and E are as described herein, pharmaceutical compositions containing such compounds, and methods of treating or preventing a disease or condition for example, cancer, mediated by the ras gene. 2. The compound or salt for use according to claim 1 , wherein Ris selected from fluorine and methoxy.3. The compound or salt for use according to claim 1 , wherein Ris selected from hydrogen claim 1 , hydroxyl claim 1 , halogen claim 1 , alkyl claim 1 , amino claim 1 , and dialkylamino.4. The compound or salt for use according to claim 3 , wherein Ris selected from hydroxy and amino.5. The compound or salt for use according to claim 1 , wherein the heterocycle of the heterocyclyl and heterocycloalkyl is selected from pyridinyl claim 1 , piperidinyl claim 1 , piperazinyl claim 1 , and pyrrolidinyl.6. The compound or salt for use according to claim 1 , wherein R′ is phenyl or arylalkyl claim 1 , optionally substituted on the phenyl or the aryl of the arylalkyl by one or more halogen atoms.7. The compound or salt for use according to claim 1 , wherein said selectivity index is at least ten.8. The compound or salt for use according to claim 7 , wherein said selectivity index is at least one hundred.9. The compound or salt for use according to claim 1 , wherein said compound is selected from:(Z)-N-(2-(dimethylamino)ethyl)-2-(1-(4-hydroxy-3,5-dimethoxybenzylidene)-5-methoxy-2-methyl-1H-inden-3-yl)acetamide (003),(Z)-2-(1-(4-hydroxy-3,5-dimethoxybenzylidene)-5-methoxy-2-methyl-1H-inden-3-yl)-N-(pyridin-3-yl)acetamide (004),(Z)-2-(1-(4-hydroxy-3,5-dimethoxybenzylidene)-5-methoxy-2-methyl-1H-inden-3-yl)-N-(pyridin-3-ylmethyl)acetamide (009),(Z)-2-(5-fluoro-1-(4-hydroxy-3,5-dimethoxybenzylidene)-2-methyl-1H-inden-3-yl)-N-(pyridin-2-ylmethyl)acetamide (010),(Z)-2-(5-fluoro-1-(4-hydroxy-3,5-dimethoxybenzylidene)-2-methyl-1H-inden-3-yl)-N-(pyridin-3-ylmethyl)acetamide (011),(Z)-N-benzyl-2-(5- ...

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Номер записи: 33
03-03-2022 дата публикации

Novel high penetration drugs and their compositions thereof for treatment of parkinson diseases

Номер: US20220064157A1
Автор: Chongxi Yu, Lina Xu
Принадлежит: Techfields Pharma Co Ltd

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

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Номер записи: 34
25-02-2021 дата публикации

CURCUMIN ANALOGUES AS ZINC CHELATORS AND THEIR USES

Номер: US20210053905A1
Автор: Golub Lorne, Johnson Francis
Принадлежит:

This invention provides a compound having the structure 134-. (canceled)43. The method of wherein Ris methoxy claim 40 , —ORor —NRR claim 40 , wherein Ris H claim 40 , Calkyl claim 40 , Calkenyl claim 40 , or Calkynyl;{'sub': 16', '17', '1-10', '2-10', '2-10, 'Rand Rare each, independently, H, Calkyl, Calkenyl, Calkynyl, aryl, heteroaryl, or heterocyclyl;'}or a salt thereof.44. The method of claim 40 , wherein{'sub': 14', '16', '17, 'Ras —NRR,'}{'sub': 16', '17, 'wherein Rand Rare each, independently, H or aryl;'}{'sub': 2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '28', '29', '28, 'R, R, R, R, R, R, R, R, R, and Rare each independently, H, —NRR, or —OR,'}{'sub': 28', '29', '1-10, 'wherein Rand Rare each, H or Calkyl;'}or a salt thereof.45. The method of claim 40 , wherein{'sub': '14', 'Ris —NH-phenyl;'}{'sub': 2', '8', '9', '7', '10', '11, 'R, R, R, R, R, and Rare each H;'}{'sub': 3', '4', '8', '9', '3, 'R, R, R, and Rare each, independently, H, —OH, or —OCH; or a salt thereof.'}48. The method of wherein the matrix metalloproteinase (MMP) is MMP-1 claim 35 , MMP-2 claim 35 , MMP-3 claim 35 , MMP-7 claim 35 , MMP-8 claim 35 , MMP-9 claim 35 , MMP-12 claim 35 , MMP-13 claim 35 , or MMP-14.50. The method of wherein the cytokine is TNF-α claim 49 , IL-1β claim 49 , MCP-1 claim 49 , or IL-6.51. The method of wherein the production of a cytokine is induced by an endotoxin claim 49 , lipopolysaccharide (LPS) claim 49 , a hormone claim 49 , or a cholesterol complex.54. The method of wherein the population of cells is a population of human cells. This application claims the benefit of U.S. Provisional Application No. 61/216,392, filed May 15, 2009, the content of which is hereby incorporated by reference in its entirety.Throughout this application, certain publications are referenced in parentheses. Full citations for these publications may be found immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by ...

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Номер записи: 35
13-02-2020 дата публикации

INDENYL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND MEDICAL USES THEREOF

Номер: US20200048217A1
Автор: Boyd Michael R., Chen Xi, KEETON Adam B., Piazza Gary A.
Принадлежит: ADT PHARMACEUTICALS, LLC

Disclosed are compounds, for example, compounds of formula I, 137-. (canceled)39. The compound claim 38 , (Z)- or (E)-isomer thereof claim 38 , or a pharmaceutically acceptable salt thereof claim 38 , of claim 38 , wherein Ris selected from hydroxyl claim 38 , hydroxyalkyl claim 38 , amino claim 38 , aminoalkyl claim 38 , mercapto and carboxyl.40. The compound claim 38 , (Z)- or (E)-isomer thereof claim 38 , or a pharmaceutically acceptable salt thereof claim 38 , of claim 38 , wherein the heterocyclyl of the heterocyclyl and heterocyclylalkyl of the R′ is selected from the group consisting of diazinyl claim 38 , oxazinyl claim 38 , thiazinyl claim 38 , dioxinyl claim 38 , dithiinyl claim 38 , thiophenyl claim 38 , imidazolidinyl claim 38 , pyrazolidinyl claim 38 , oxazolidinyl claim 38 , isoxazolidinyl claim 38 , dioxolanyl claim 38 , dithiolanyl claim 38 , imidazolyl claim 38 , pyrazolyl claim 38 , oxazolyl claim 38 , isoxazolyl claim 38 , thiazolyl claim 38 , isothiazolyl claim 38 , furazanyl claim 38 , and oxadiazolyl.41. The compound claim 38 , (Z)- or (E)-isomer thereof claim 38 , or a pharmaceutically acceptable salt thereof claim 38 , of claim 38 , wherein the heterocyclyl of the heterocyclyl and heterocyclylalkyl of the R′ is selected from diazinyl claim 38 , thiophenyl claim 38 , oxazolyl claim 38 , isoxazolyl claim 38 , thiazolyl claim 38 , isothiazolyl claim 38 , dioxolanyl claim 38 , pyrazolyl and imidazolyl claim 38 , wherein the heterocyclyl is optionally substituted with one or more of halo claim 38 , alkyl claim 38 , haloalkyl claim 38 , hydroxyl claim 38 , alkoxy claim 38 , amino claim 38 , alkylamino claim 38 , dialkylamino claim 38 , mercapto claim 38 , alkylmercapto claim 38 , and carboxamido.42. The compound claim 41 , (Z)- or (E)-isomer thereof claim 41 , or a pharmaceutically acceptable salt thereof claim 41 , of claim 41 , wherein the heterocyclyl of the heterocyclyl and heterocyclylalkyl of the R′ is selected from oxazolyl claim 41 , ...

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Номер записи: 36
13-02-2020 дата публикации

COMPOSITIONS AND METHODS FOR MODULATING PROTEASE ACTIVITY

Номер: US20200048227A1
Автор: Chang Fang-Yuan, CLARDY Jon, Fischbach Michael A., Guo Chun-Jun, Voigt Christopher A., Wyche Thomas
Принадлежит:

Disclosed herein, inter alia, are compositions for modulating protease activity and treating cancer. 2. The compound claim 1 , of claim 1 , wherein when Ris —B(OH) claim 1 , Ris independently hydrogen claim 1 , —C(O)R claim 1 , or —C(O)—OR; and{'sup': '1C', 'sub': 3', '3', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2, 'Ris hydrogen, —CF, —Cl, —CI, —CBr, —COOH, —CONH, —CHF, —CHCl, —CHI, —CHBr, —OCHF, —OCHCl, —OCHI, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl.'}312.-. (canceled)14. The compound of claim 1 , wherein Ris —C(O)H.15. The compound claim 1 , of claim 1 , wherein when Ris —C(O)H claim 1 , Ris —C(O)R claim 1 , or —C(O)—OR.1624.-. (canceled)34. The compound claim 1 , of claim 1 , wherein at least one N is N claim 1 , at least one C is C claim 1 , or at least one H is H.35. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient.36. A method of treating cancer claim 1 , said method comprising administering to a subject in need thereof an effective amount of a compound of .37. A method of inhibiting cathepsin activity claim 1 , said method comprising: contacting the cathepsin with a compound of .38. (canceled)39. A method of reducing cathepsin activity claim 1 , said method comprising: contacting the cathepsin with a compound of .40. (canceled)41. (canceled)42. A method of inhibiting protease activity claim 1 , said method comprising: contacting the protease with a compound of .4345.-. (canceled) This application is the national stage filing under USC 371 of international application PCT/US2017/061840, filed Nov. 15, 2017, which claims the benefit of U.S. Provisional Application No. 62/426,012, filed Nov. 23, 2016, which are incorporated herein by reference in their entirety and for all purposes.This invention was made with government support under grant no. ...

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Номер записи: 37
08-05-2014 дата публикации

PESTICIDAL DIARYL - HETEROCYCLYL DERIVATIVES

Номер: US20140128614A1
Автор: Bruechner Peter, Hatazawa Mamoru, Ichihara Teruyuki, Ishikawa Tadashi, Murata Tetsuya, Shibuya Katsuhiko, Shimojo Eiichi, Yamazaki Daiei
Принадлежит: Bayer Intellectual Property GmbH

To provide pesticidal allylAryl heterocycle derivatives that are useful as a pesticidal compound. 2. The allylAryl heterocycle derivative according to claim 1 , in which{'sub': 1-6', '1-6, 'R′ represents Calkyl or Chaloalkyl,'}{'sub': 1', '2', '3', '4, 'A, A, Aand Aeach independently represent C—Y or N,'}{'sub': 1', '2', '3', '4, 'B, B, Band Beach independently represent C—X or N,'}{'sub': 5', '1-6', '3-7', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6, 'X and Y each independently represent hydrogen, halogen, nitro, cyano, hydroxy, mercapto, amino, SF, Calkyl, Ccycloalkyl, Calkoxy, Calkylthio, Calkylsulfinyl, Calkylsulfonyl, Calkylsulfonyloxy, Calkylaminosulfonyl, di(Calkyl)amino-sulfonyl, Calkyl-carbonylamino, benzoylamino, tri(Calkyl)silyl, Calkoxyimino, Calkylsulfinylimino, Calkylsulfonylimino, Calkoxy-carbonyl, Calkyl-carbonyl, aminocarbonyl, Calkylamino-carbonyl, aminothiocarbonyl, Calkylamino-thiocarbonyl, di(Calkyl)amino-carbonyl or di(Calkyl)amino-thiocarbonyl, and herein, each group from Calkyl to di(Calkyl)amino-thiocarbonyl above may be optionally substituted with halogen,'}{'sup': 1', '2, 'sub': 1-6', '3-7', '3-7', '1-6', '2-6', '2-6', '1-6', '1-6', '1-6', '1-6, 'Rand Reach independently represent hydrogen, cyano, Calkyl, Ccycloalkyl, Ccycloalkyl-Calkyl, Calkenyl, Calkynyl, Calkoxy-carbonyl or Cthioalkoxy-carbonyl, and herein, each group from Calkyl to Cthioalkoxy-carbonyl above may be optionally substituted with halogen,'}{'sup': 1', '2, 'or Rand Rmay form, together with the carbon atom to which they are bound, a 3- to 6-membered hydrocarbon ring,'}{'sup': '1', 'sub': 2', '2-3', '2, 'or Rmay form, together with Y of A, Calkylene when n represents 1 and Arepresents C—Y,'}{'sup': 3', '5', '5', '5, 'sub': 1-6', '1-6', '1-6', '1-6', '3-7', '2-6', '2-6', '1-6', '2', '1-6', '1-6, 'Rrepresents hydrogen, amino, hydroxy, cyano, Calkyl, Calkoxy, Calkyl-carbonylamino, ...

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Номер записи: 38
05-06-2014 дата публикации

ENZYME INHIBITORS

Номер: US20140155439A1
Автор: Belfield Andrew James, Donald Alastair David Graham, Jones Stewart Andrew Wayne, Moffat David Festus Charles, North Carl Leslie
Принадлежит: Chroma Therapeutics Ltd.

Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent ═CH— or ═N—; W is —CH═CH— Or —CHCH—; Ris a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; Rand Rare selected from the side chains of a natural or non-natural alpha amino acid, provided that neither Rnor Ris hydrogen, or Rand R, taken together with the carbon to which they are attached, form a 3-6 membered saturated cycloalkyl or heterocyclyl ring; Y is a bond, —C(C═O)—, —S(═O)—, —C(C═O)O—, —C(C═O)NR′—, —C(═S)—NR′, —C(═NH)NR′ or —S(═O)NR— wherein R′ is hydrogen or optionally substituted C-Calkyl; Lis a divalent radical of formula -(Alk)(Q)(Alk)— wherein in, n, p, Q, AIkand AIkare as defined in the claims; Xrepresents a bond; —C(═O); or —S(═O)—; —NRC(═O)—, —C(C═O)NR—, —NRC(═O)NR—, —NRS(═O)—, or —S(═O)NR— wherein Rand Rare independently hydrogen or optionally substituted C-Calkyl; and z is 0 or 1. 2. A compound as claimed in wherein A claim 1 , B and D are each ═CH—.3. A compound as claimed in wherein one of A claim 1 , B and D is ═N— and the others are each ═CH—.4. A compound as claimed in any of the preceding claims wherein the radical HONHC(═O)—W— is attached to the ring containing A claim 1 , B and C in a position meta- or para- to the radical RRRC-NHYLX[CH]—.5. A compound as claimed in any of the preceding claims wherein claim 1 , in the radical RRRC-NHYLX[CH]— claim 1 , z is 0.6. A compound as claimed in any of the preceding claims wherein claim 1 , in the radical RRRC-NHYLX[CH]— claim 1 , Y is a bond.7. A compound as claimed in any of to wherein claim 1 , in the radical RRRC-NHYLX[CH]— claim 1 , Xis a bond.8. A compound as claimed in any of to wherein claim 1 , in the radical RRRC-NHYLX[CH]— claim 1 , z is 0 claim 1 , Y and Xare each a bond claim 1 , and Cis a divalent radical of formula -(Alk)(Q)(Alk)- wherein one of m and p is 0 and the other is 1 claim 1 , and n is ...

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Номер записи: 39
18-03-2021 дата публикации

SELECTIVE HISTONE DEACETYLASE INHIBITORS FOR THE TREATMENT OF HUMAN DISEASE

Номер: US20210078963A1
Автор: Dritschilo Anatoly, GRINDROD Scott, Jung Mira
Принадлежит:

Selective HDAC inhibitors, and pharmaceutical compositions that include the same, are described herein for the treatment of cancer, immunological diseases, inflammatory diseases, and neurological diseases. 5. The compound of claim 1 , wherein the compound is a selective HDAC6 inhibitor.6. A pharmaceutical composition comprising a histone deacetylase (HDAC) inhibitor of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , hydrate claim 1 , cocrystal claim 1 , or prodrug thereof.7. A method of treating a disease alleviated by inhibiting histone deacetylase (HDAC) protein in a patient in need thereof claim 6 , wherein the treatment comprises administering a therapeutically effective amount of the pharmaceutical composition of .8. The method of claim 6 , wherein the disease is selected from the group consisting of cancer claim 6 , an immunological disease claim 6 , an inflammatory disease claim 6 , and a neurological disease.9. The method of claim 8 , wherein the cancer is selected from the group consisting of acoustic neuroma claim 8 , adenocarcinoma claim 8 , angiosarcoma claim 8 , astrocytoma claim 8 , basal cell carcinoma claim 8 , bile duct carcinoma claim 8 , bladder carcinoma claim 8 , brain cancer claim 8 , breast cancer claim 8 , brochogenic carcinoma claim 8 , cervical cancer claim 8 , chordoma claim 8 , choriocarcinoma claim 8 , colon cancer claim 8 , colorectal cancer claim 8 , craniopharygioma claim 8 , cystadenocarcinoma claim 8 , embryonal carcinoma claim 8 , endotheliocarconima claim 8 , ependymoma claim 8 , epithelial carcinoma claim 8 , esophageal cancer claim 8 , Ewing's tumor claim 8 , fibrosarcoma claim 8 , gastric cancer claim 8 , glioblastoma multiforme claim 8 , glioma claim 8 , head and neck cancer claim 8 , hemangioblastoma claim 8 , hepatoma claim 8 , kidney cancer claim 8 , leiomyosarcoma claim 8 , liposarcoma claim 8 , lung cancer claim 8 , lymphangioendotheliosarcoma claim 8 , lymphangiosarcoma claim 8 , medullary ...

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Номер записи: 40
22-03-2018 дата публикации

BETA-SUBSTITUTED BETA-AMINO ACIDS AND ANALOGS AS CHEMOTHERAPEUTIC AGENTS

Номер: US20180078517A1
Автор: Fischer Wolf-Nicolas, Jandeleit Bernd, Koller Kerry J.
Принадлежит:

β-Substituted β-amino acids, β-substituted β-amino acid derivatives, and β-substituted β-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types. 1. A method of treating cancer in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of (3S)-3-amino-4-[5-[bis(2-chloroethyl)amino]-2-methyl-phenyl]butanoic acid (5) , or a pharmaceutically acceptable salt thereof.2. The method of claim 1 , wherein administering comprises administering a pharmaceutical composition claim 1 , wherein the pharmaceutical composition comprises:a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof; anda pharmaceutically acceptable vehicle.3. The method of claim 1 , wherein the cancer comprises cancerous tissue that over-expresses the LAT1/4F2hc compared to surrounding non-cancerous tissue.4. The method of claim 1 , wherein the cancer is known to be treated by administering an alkylating agent.5. The method of claim 1 , wherein the cancer is in the brain of the patient.6. The method of claim 1 , wherein the cancer comprises brain cancer.7. The method of claim 6 , wherein the brain ...

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Номер записи: 41
12-06-2014 дата публикации

LYSINE DEMETHYLASE INHIBITORS FOR MYELOPROLIFERATIVE OR LYMPHOPROLIFERATIVE DISEASES OR DISORDERS

Номер: US20140163041A1
Автор: Fyfe Matthew Colin Thor, Maes Tamara, MARTINELL PEDEMONTE Marc
Принадлежит: ORYZON GENOMICS S.A.

The present invention relates to methods and compositions for the treatment or prevention of diseases and disorder associated with myeloproliferative and lymphoproliferative disorders. In particular, the invention relates to an LSD1 inhibitor for use in treating or preventing diseases and disorder associated with myeloproliferative and lymphoproliferative disorders. 12-. (canceled)3. A method of treating or preventing a hematological cancer comprising administering to an individual a therapeutically effective amount of a LSD1 inhibitor.4. (canceled)5. The method of claim 3 , wherein said hematological cancer is a hematological cancer caused by or related to myeloproliferation.6. The method of claim 3 , wherein said hematological cancer is acute myelogenous leukemia (AML) claim 3 , chronic myelogenous leukemia (CML) claim 3 , chronic neutrophilic leukemia claim 3 , or chronic eosinophilic leukemia.7. The method of claim 3 , wherein said hematological cancer is a hematological cancer caused by or related to lymphoproliferation.8. The method of claim 3 , wherein said hematological cancer is follicular lymphoma claim 3 , chronic lymphocytic leukemia (CLL) claim 3 , acute lymphoblastic leukemia (ALL) claim 3 , hairy cell leukemia claim 3 , lymphoma claim 3 , multiple myeloma claim 3 , or Waldenstrom's macroglobulinemia.9. The method of claim 3 , wherein said hematological cancer is a lymphoma chosen from precursor B-lymphoblastic leukemia/lymphoma claim 3 , B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma claim 3 , B-cell prolymphocytic leukemia claim 3 , lymphoplasmacytic lymphoma claim 3 , splenic marginal zone B-cell lymphoma (+/− villous lymphocytes) claim 3 , hairy cell leukemia claim 3 , plasma cell myeloma/plasmacytoma claim 3 , extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type claim 3 , nodal marginal zone lymphoma (+/− monocytoid B-cells) claim 3 , follicle center lymphoma claim 3 , follicular claim 3 , mantle cell ...

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Номер записи: 42
12-05-2022 дата публикации

Novel aminoalkanoic acid derivative containing biphenyl group and antifungal pharmaceutical composition comprising the same

Номер: US20220144755A1
Автор: Eunji Cheong, Hyeon Ji Kim, Ji Won Choi, Jong Hyun Park, Jong-Seung Lee, Joohyeon Hong, Ki Duk Park, Kyung-Tae Lee, Seul Ki YEON, Siwon KIM, Ye Rim LEE, Yong-Sun Bahn
Принадлежит: Amtixbio Co Ltd

The present invention relates to a derivative compound in which a biphenyl group is introduced into an aminoalkanoic acid, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. The compound of the present invention exhibits excellent antifungal and fungicidal effects. Furthermore, the compound of the present invention exhibits a synergistic effect when used in combination with a conventional antifungal agent. Furthermore, the compound of the present invention provides broad-spectrum antifungal activity against a wide range of fungal pathogens. Therefore, the compound of the present invention may be widely used in fields requiring treatment with antifungal or fungicidal agents against human pathogenic fungi and animal pathogenic fungi, and phytopathogenic fungi.

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Номер записи: 43
28-03-2019 дата публикации

Compounds, pharmaceutical composition and their use in treating neurodegenerative diseases

Номер: US20190092721A1
Автор: Bénédicte Oxombre-Vanteghem, Héléne Zephir, Marion Donnier-Marechal, Pascal Carato, Patricia Melnyk, Patrick Vermersch
Принадлежит: Centre Hospitalier Regional Universitaire de Lille CHRU, Universite Lille 2 Droit et Sante

The present invention is directed to novel compounds of Formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.

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Номер записи: 44
12-04-2018 дата публикации

USE OF (2R, 6R)-HYDROXYNORKETAMINE, (S)-DEHYDRONORKETAMINE AND OTHER STEREOISOMERIC DEHYDRO AND HYDROXYLATED METABOLITES OF (R,S)- KETAMINE IN THE TREATMENT OF DEPRESSION AND NEUROPATHIC PAIN

Номер: US20180098993A1
Автор: BERNIER Michel, GOLDBERG MICHAEL E., Moaddel Ruin, TANGA MARY J., TORJMAN MARC C., Wainer Irving W., Zarate Carlos A.
Принадлежит:

The disclosure provides pharmaceutical preparations containing (2R,6R)-hydroxynorketamine, or (R)- or (S)-dehydronorketamine, or other stereoisomeric dehydro or hydroxylated ketamine metabolite. 5. The pharmaceutical composition of claim 1 , wherein the composition is formulated for oral administration claim 1 , intravenous administration claim 1 , or intramuscular injection.6. The pharmaceutical composition of claim 1 , wherein the composition is a solution and contains from about 0.05 mg/ml to about 0.5 mg/ml.7. The pharmaceutical composition of claim 1 , wherein the composition is formulated as an oral dosage form containing about 0.2 mg to about 500 mg of the compound.11. A compound or salt of claim 9 , wherein{'sub': '1', 'Ris hydrogen or hydroxyl;'}{'sub': '3', 'Ris hydrogen or methyl;'}{'sub': 4', '5', '1', '2', '1', '2, 'Rand Rare each 0 to 2 substituents independently chosen from halogen, hydroxyl, amino, C-Calkyl, and C-Calkyl; and'}{'sub': '6', 'Ris hydrogen or methyl.'}12. A compound or salt of claim 11 , wherein{'sub': 2', '2', '2', '2', '2', '6', '6', '2', '1', '6', '2', '4', '0', '2', '3', '7', '0', '4', '0', '2', '0', '2', '2', '1', '4', '1', '4', '1', '6', '1', '4', '1', '2', '1', '2, 'Ris -ABwhere Ais a bond, —(C═O)O—, —S(O)—, —(S═O)NR—, or —(C═O)NR—, Bis C-Calkyl, C-Calkanoyl, (phenyl)C-Calkyl, (C-Ccycloalkyl)C-Calkyl, (heterocycloalkyl)C-Calkyl, (5- or 6-membered heteroaryl)C-Calkyl, or an amino acid covalently bound to Aby its C-terminus, each of which is substituted with from 0 to 4 substituents independently chosen from halogen, hydroxyl, amino, cyano, C-Calkyl, C-Calkoxy, C-Calkylester, mono- and di-(C-Calkyl)amino, C-Chaloalkyl, and C-Chaloalkoxy.'}13. A compound or salt of claim 12 , wherein{'sub': 2', '2', '2, 'Ais a bond and Bis an amino acid covalently bound to Aby its C-terminus.'}15. A compound or salt of claim 11 , where{'sub': 2', '2', '2', '6', '2', '3', '7', '0', '4', '1', '4', '1', '4', '1', '4, 'Ais a bond or —(C═O)O— and Bis C- ...

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Номер записи: 45
12-04-2018 дата публикации

INHIBITORS OF HISTONE DEACETYLASE

Номер: US20180099977A1
Автор: Haggarty Stephen J., Holson Edward, Tsai Li-Huei, Wagner Florence Fevrier, Weiwer Michel, ZHANG YAN-LING
Принадлежит:

The present invention relates to compounds of formula (I): 10. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.11. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.12. The method of claim 11 , wherein the condition is selected from a neurological disorder claim 11 , memory loss or impairment claim 11 , cognitive function disorder or impairment claim 11 , extinction learning disorder claim 11 , fungal disease or infection claim 11 , inflammatory disease claim 11 , hematological disease claim 11 , and neoplastic disease.13. The method of claim 11 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, phobia, social anxiety disorder, substance dependence recovery or Age Associated Memory Impairment (AAMI), or Age Related Cognitive Decline (ARCD);a hematological disease selected from acute myeloid leukemia, acute promyelocytic leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, myelodysplastic syndromes, and sickle cell anemia;a cancer; andan extinction learning disorder selected from a fear extinction deficit and post-traumatic ...

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Номер записи: 46
20-04-2017 дата публикации

Compounds, pharmaceutical composition and their use in treating neurodegenerative diseases

Номер: US20170107174A1
Автор: Bénédicte Oxombre-Vanteghem, Héléne Zephir, Marion Donnier-Marechal, Pascal Carato, Patricia Melnyk, Patrick Vermersch
Принадлежит: Centre Hospitalier Regional Universitaire de Lille CHRU, Universite Lille 2 Droit et Sante

The present invention is directed to novel compounds of Formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.

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Номер записи: 47
20-04-2017 дата публикации

HETEROCYCLIC INHIBITORS OF THE SODIUM CHANNEL

Номер: US20170107203A1
Автор: Holland Richard, Lamontagne Jason, PAJOUHESH Hassan, Pajouhesh Hossein, Whelan Brendan, ZHANG Lingyun
Принадлежит:

The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention concerns heterocyclic compounds (e.g., compounds according to any of Formulas (1)-(X) or Compounds (1)-(92) of Table 1) that are that are useful in treatment of conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome. 3. The compound of claim 1 , wherein Ar is unsubstituted phenyl or Ar is phenyl having 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , or 5 substituents selected independently from optionally substituted C1-C6 alkyl claim 1 , optionally substituted C1-C6 alkoxy claim 1 , O-(optionally substituted phenyl) claim 1 , optionally substituted phenyl claim 1 , —SO-(optionally substituted phenyl) claim 1 , —SO-(optionally substituted alkyl) claim 1 , and halogen.4. The compound of or claim 1 , wherein Ar comprises a halogen substituent.5. The compound of any of - claim 1 , wherein Rand Rare both H.6. The compound of claim 1 , wherein Rand Ar together form a dihydroindole moiety.7. The compound of claim 1 , wherein Rand Ar together form an indane moiety.8. The compound of any of - claim 1 , wherein m is 0 and n is 0.9. The compound of any of - claim 1 , wherein m is 1 and n is O.10. The compound of any of - claim 1 , wherein m is 0 and n is 1.11. The compound of any of - claim 1 , wherein m is 1 and n is 1.12. The compound of claim 1 , wherein said compound is selected from compounds 51-59 in Table 1.14. The compound of claim 13 , wherein Ris H.15. The compound of or claim 13 , wherein Lis an optionally substituted C1-C3 alkylene that is linear or branched.16. The compound of claim 15 , wherein said C1-C3 alkylene is unsubstituted.17. ...

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Номер записи: 48
09-04-2020 дата публикации

Mu opioid receptor modulators

Номер: US20200109126A1
Автор: Aashish Manglik, Brian K. Shoichet, Brian Kobilka, Bryan L. Roth, Daniela Gisela DENGLER, Harald Hübner, Peter Gmeiner
Принадлежит: Friedrich Alexander Univeritaet Erlangen Nuernberg FAU, Leland Stanford Junior University, UNIVERSITY OF CALIFORNIA, UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL

Described herein, inter alia, are compositions and methods for modulating mu opioid receptor activity.

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Номер записи: 49
03-05-2018 дата публикации

SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF

Номер: US20180118663A1
Автор: COSS Christopher C., Dalton James T., DUKE Charles B., Hwang Dong-Jin, JONES Amanda, Miller Duane D., NARAYANAN Ramesh, PONNUSAMY Thamarai
Принадлежит:

This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject. 2. The method of claim 1 , wherein said cancer is a cancer associated with partial androgen insensitivity syndromes (PAIS) claim 1 , cancer of the fallopian tubes or peritoneum claim 1 , salivary gland cancer claim 1 , esophageal cancer claim 1 , bladder cancer claim 1 , melanoma claim 1 , mantle cell lymphoma claim 1 , hepatocellular carcinoma claim 1 , renal cell carcinoma claim 1 , non-small cell lung cancer (NSCLC) claim 1 , gastric cancer claim 1 , and/or colon cancer.3. The method of claim 2 , wherein the cancer associated with partial androgen insensitivity syndromes (PAIS) is gonadal tumors and/or seminoma.9. The method of claim 8 , wherein said hyperandrogenic hormonal condition in a female is precocious puberty claim 8 , early puberty claim 8 , dysmenorrhea claim 8 , amenorrhea claim 8 , multilocular uterus syndrome claim 8 , endometriosis claim 8 , hysteromyoma claim 8 , abnormal uterine bleeding claim 8 , early menarche claim 8 , fibrocystic breast disease claim 8 , fibroids of the uterus claim 8 , ovarian cysts claim 8 , polycystic ovary syndrome claim 8 , pre-eclampsia claim 8 , eclampsia of pregnancy claim 8 , preterm labor claim 8 , premenstrual syndrome claim 8 , and/or vaginal dryness.11. The topical pharmaceutical composition of claim 10 , wherein said composition is in the form of a solution claim 10 , lotion claim 10 , salve claim 10 , cream claim ...

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Номер записи: 50
25-08-2022 дата публикации

L-Y-METHYLENEGLUTAMINE COMPOUNDS AND METHODS OF USE

Номер: US20220267255A1
Автор: HOSSAIN Md. Imran, Le Hoang Van
Принадлежит:

Disclosed are substantially pure L-y-methyleneglutamine, L-y-methyleneglutamic acid, and/or amide derivatives, and methods of use thereof. In particular, the presently disclosed subject matter relates to L-y-methyleneglutamine, L-y-methyleneglutamic acid, and/or amide derivatives thereof, and methods of treating cancer. The method comprises administering one or more substantially pure L-y-methyleneglutamine, L-y-methyleneglutamic acid, and/or amide derivatives to a subject in need thereof. 110-. (canceled)12. The compound of claim 11 , wherein Ris an alkyl group substituted with an aryl group.13. The compound of claim 11 , wherein Ris unsubstituted or substituted benzyl group.14. The compound of claim 11 , wherein Ris an alkyl group substituted with an aryl group claim 11 , wherein the aryl group is substituted with one or more of a halogen claim 11 , haloalkyl claim 11 , or NO.15. The compound of claim 14 , wherein the halogen is F or Cl.16. The compound of claim 11 , wherein Ris a benzyl group or a benzyl group substituted with one or more of a halogen claim 11 , haloalkyl claim 11 , or NO.17. The compound of claim 11 , wherein Ris H and Ris an alkyl group substituted with an aryl group.18. The compound of claim 17 , wherein the aryl group is substituted with one or more of a halogen or NO.19. The compound of claim 11 , wherein{'sup': '2', 'Rincludes H or tert-butoxycarbonyl (BOC);'}{'sup': '3', 'sub': 2', '3;, 'Rincludes OH, tert-butoxy or OCHCHand'}{'sup': '4', 'Rincludes substituted or unsubstituted aryl, phenyl, benzyl.'}21. The compound of claim 20 , wherein Ris H and X is halogen or NO.23. The compound of claim 22 , wherein Ris H and X is halogen or NO.24. A method of treating cancer claim 11 , the method comprising administering one or more compounds according to to a subject in need thereof.25. The method of claim 24 , wherein the cancer includes claim 24 , but is not limited to claim 24 , common cancers claim 24 , rare cancers claim 24 , breast cancer ...

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Номер записи: 51
14-05-2015 дата публикации

COMPOSITIONS AND METHODS FOR THE TREATMENT OF RESPIRATORY DISORDERS

Номер: US20150133407A1
Автор: Kandula Mahesh
Принадлежит:

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of respiratory disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of viscid or excessive mucus, cough, inflammation, redness in sore throat, infection in the throat, sore throat, abnormal mucus secretion, impaired mucus transport, allergic rhinitis, asthma, COPD, respiratory muscular disorders and pain in acute sore throat. 2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.3. The pharmaceutical composition of claim 2 , wherein said pharmaceutical composition is formulated to treat the underlying etiology with an effective amount administering the patient in need by oral administration claim 2 , delayed release or sustained release claim 2 , transmucosal claim 2 , syrup claim 2 , topical claim 2 , parenteral administration claim 2 , injection claim 2 , subdermal claim 2 , oral solution claim 2 , rectal administration claim 2 , buccal administration or transdermal administration.4. A method of treating respiratory disorders related diseases as the underlying etiology claim 3 , wherein the method comprises administering to a patient in need thereof an effective amount of .5. The method of claim 4 , wherein the respiratory disorders as the underlying etiology is selected from viscid or excessive mucus claim 4 , cough claim 4 , inflammation claim 4 , redness in sore throat claim 4 , infection in the throat claim 4 , sore throat claim 4 , abnormal mucus secretion claim 4 , impaired mucus transport claim 4 , allergic rhinitis claim 4 , asthma claim 4 , COPD claim 4 , respiratory muscular ...

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Номер записи: 52
31-07-2014 дата публикации

BENZYLAMINE DERIVATIVES AS INHIBITORS OF PLASMA KALLIKREIN

Номер: US20140213611A1
Автор: DAVIE Rebecca Louise, EDWARDS Hannah Joy, EVANS David Michael, ROOKER David Philip
Принадлежит: Kalvista Pharmaceuticals Limited

The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease or condition in which plasma kallikrein activity is implicated); and methods of treating patients with such compounds; wherein Rto Rare as defined herein. 2. A compound 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.3. A compound 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.4. A compound of claim 1 , wherein Ris H claim 1 , —COaryl claim 1 , —COalkyl claim 1 , —CHCOOH claim 1 , —SOPh claim 1 , or —SOCH.5. A compound of claim 1 , wherein Ris —COalkyl or —COaryl.7. A compound of claim 1 , wherein Rand Rare independently H or CH.8. A compound of claim 1 , wherein the stereochemical configuration about chiral centre *1 is R.9. A compound of claim 1 , wherein the stereochemical configuration about chiral centre *2 is S.10. A compound 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 , l and m are each 1.11. A compound as claimed in claim 1 , the compound being:(S)—N-(4-Aminomethyl-benzyl)-2-[(R)-3-(4-ethoxy-phenyl)-2-propionylamino-propionylamino]-3-phenyl-propionamide;N—[(R)-1-[(S)-1-(4-Aminomethyl-benzylcarbamoyl)-2-phenyl-ethylcarbamoyl]-2-(4-ethoxy-phenyl)-ethyl]-benzamide;{(R)-1-[(S)-1-(4-Aminomethyl-benzylcarbamoyl)-2-phenyl-ethylcarbamoyl]-2-cyclohexyl-ethylamino}-acetic acid;(S)—N-(4-Aminomethyl-3-fluoro-benzyl)-2-[(R)-3-(4-ethoxy-phenyl)-2-propionylamino-propionylamino]-3-phenyl-propionamide ...

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Номер записи: 53
01-09-2022 дата публикации

IMMUNOREGULATORY AGENTS

Номер: US20220274926A1
Автор: Balog James Aaron, BECK Hilary Plake, Guo Weiwei, JAEN Juan Carlos, OSIPOV Maksim, POWERS Jay Patrick, REILLY Maureen Kay, SHUNATONA Hunter Paul, WALKER James Ross, Williams David K., ZIBINSKY Mikhail
Принадлежит:

Compounds that modulate the oxidoreductase enzyme indoleamine 2,3-dioxygenase, and compositions containing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by indoleamine 2,3-dioxygenase is also provided. 238-. (canceled)39. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.40. A method of treating cancer claim 1 , said method comprising administering an effective amount of a compound of claim 1 , to a subject in need thereof.41. A method of claim 40 , wherein said compound is administered concurrently with claim 40 , subsequent to claim 40 , or prior to claim 40 , radiation treatment.4245-. (canceled)46. A method of claim 40 , wherein said cancer is a cancer of the prostate claim 40 , colon claim 40 , rectum claim 40 , pancreas claim 40 , cervix claim 40 , stomach claim 40 , endometrium claim 40 , brain claim 40 , liver claim 40 , bladder claim 40 , ovary claim 40 , testis claim 40 , head claim 40 , neck claim 40 , skin (including melanoma and basal carcinoma) claim 40 , mesothelial lining claim 40 , white blood cell (including lymphoma and leukemia) claim 40 , esophagus claim 40 , breast claim 40 , muscle claim 40 , connective tissue claim 40 , lung (including small-cell lung carcinoma and non-small-cell carcinoma) claim 40 , adrenal gland claim 40 , thyroid claim 40 , kidney claim 40 , or bone; or is glioblastoma claim 40 , mesothelioma claim 40 , renal cell carcinoma claim 40 , gastric carcinoma claim 40 , sarcoma (including Kaposi's sarcoma) claim 40 , choriocarcinoma claim 40 , cutaneous basocellular carcinoma claim 40 , or testicular seminoma.47. A method of claim 40 , wherein said cancer is selected from the group consisting of melanoma claim 40 , colon cancer claim 40 , pancreatic cancer claim 40 , breast cancer claim 40 , ...

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Номер записи: 54
08-09-2022 дата публикации

CYCLOPROPYL-AMIDE COMPOUNDS AS DUAL LSD1/HDAC INHIBITORS

Номер: US20220281815A1
Автор: DEWANG Purushottam, GAJENDRAN Chandru, HALLUR Mahanandeesha S., IYER Pravin, KUMAR C.H. Durga Prasanna, MULAKALA Chandrika, MURUGAN Kannan, NAIR Sreekala, RAJAGOPAL Sridharan, Rajagopal Sriram, SIVANANDHAN Dhanalakshmi, TANTRY Subramanyam Janardhan, ZAINUDDIN Mohd
Принадлежит:

The present disclosure describes novel compounds of the general Formula (I), their analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites, and prodrugs thereof. These compounds can inhibit both LSD and HDAC and are useful as therapeutic or ameliorating agent for diseases that are involved in cellular growth such as malignant tumors, schizophrenia, Alzheimer's disease, parkinson's disease and the like. 133-. (canceled)35. The method of claim 34 , wherein the condition is mediated by both LSD1 and HDAC1.36. The method of claim 34 , wherein the condition is mediated by both LSD1 and HDAC6.37. The method of claim 34 , wherein the condition is mediated by HDAC.38. The method of claim 34 , wherein the condition is a proliferative disorder or cancer.39. The method of claim 34 , wherein the condition is cancer.40. The method of claim 39 , wherein the cancer is breast cancer claim 39 , prostate cancer claim 39 , pancreatic cancer claim 39 , gastric cancer claim 39 , lung cancer claim 39 , colon cancer claim 39 , rectal cancer claim 39 , esophagus cancer claim 39 , duodenal cancer claim 39 , tongue cancer claim 39 , pharyngeal cancer claim 39 , brain tumor claim 39 , neurinoma claim 39 , non-small cell lung cancer claim 39 , small cell lung cancer claim 39 , liver cancer claim 39 , kidney cancer claim 39 , bile duct cancer claim 39 , uterine body cancer claim 39 , cervical cancer claim 39 , ovarian cancer claim 39 , urinary & bladder cancer claim 39 , skin cancer claim 39 , hemangioma claim 39 , malignant lymphoma claim 39 , malignant melanoma claim 39 , thyroid cancer claim 39 , bone tumor claim 39 , vascular fibroma claim 39 , retinoblastoma claim 39 , penile cancer claim 39 , pediatric solid cancer claim 39 , Myelodysplastic syndrome (MDS) claim 39 , lymphoma claim 39 , myeloma claim 39 , leukemia claim 39 , acute myelogenous leukemia (AML) claim 39 , chronic myelogenous leukemia ...

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Номер записи: 55
30-04-2020 дата публикации

DUAL MECHANISM INHIBITORS FOR THE TREATMENT OF DISEASE

Номер: US20200131171A1
Автор: deLong Mitchell A., Royalty Susan M., Sturdivant Jill Marie
Принадлежит:

Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved. 1. A method of treating glaucoma or ocular hypertension , comprising administration of a composition comprising a Rho kinase inhibitor and a pharmaceutically acceptable carrier to a subject in need thereof ,wherein the administration is daily administration, weekly administration, or monthly administration.2. The method of claim 1 , wherein the administration is ocular administration.3. The method of claim 1 , wherein the amount of the Rho kinase inhibitor administered is about 0.001 to about 100 mg/kg subject body weight.4. The method of claim 1 , wherein the administration is daily administration once daily claim 1 , twice per day claim 1 , or 4 times per day.5. The method of claim 2 , wherein the administration is daily administration once daily claim 2 , twice per day claim 2 , or 4 times per day.6. The method of claim 3 , wherein the administration is daily administration once daily claim 3 , twice per day claim 3 , or 4 times per day.7. The method of claim 1 , wherein the administration is weekly administration once weekly or twice weekly.8. The method of claim 2 , wherein the administration is weekly administration once weekly or twice weekly.9. The method of claim 3 , wherein the administration is weekly administration once weekly or twice weekly.10. The method of claim 1 , wherein the administration is monthly administration once a month.11. The method of claim 2 , wherein the administration is monthly administration once a month.12. The method of claim 3 , wherein the ...

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Номер записи: 56
26-05-2016 дата публикации

Aminomethyl-Biaryl Derivatives Complement Factor D inhibitors and uses thereof

Номер: US20160145247A1
Автор: Anna Vulpetti, Christine Fang GELIN, David Belanger, Donglei Liu, Edwoge Liliane Jeanne LORTHIOIS, James J. Powers, Keith Jendza, NAN Ji, Nello Mainolfi, Oliver Rogel, Rajeshri Ganesh Karki, Stefan Andreas Randi, Stefanie Flohr, Taeyoung Yoon
Принадлежит: NOVARTIS AG

The present invention provides a compound of formula (I), a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

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Номер записи: 57
25-05-2017 дата публикации

ANTIMICROBIAL CONJUGATES, METHOD FOR PRODUCTION AND USES THEREOF

Номер: US20170144969A1
Автор: Carroll Miles, HALDAR Jayanta, Konai Mohini Mohan
Принадлежит:

The present disclosure relates to polyamine conjugates, its isomers, prodrugs and pharmaceutically acceptable salts thereof. The present disclosure also relates to process of preparation of polyamine conjugates, its stereoisomers, prodrugs, pharmaceutically acceptable salts thereof, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases mediated by microbes. 2. The compound as claimed in or its stereoisomers claim 1 , pharmaceutically acceptable salts claim 1 , polymorphs claim 1 , solvates and hydrates thereof wherein claim 1 , Y is —CH2- or —CO—;{'sub': 1', '2, 'Aand Aare same or different, and independently selected from 2 amino acid residues, wherein the amino acids are independently selected from L-configuration or D-configuration; R is selected from C4-28 alkyl, C6-18 aryl.'}3. The compound as claimed in or its stereoisomers claim 1 , pharmaceutically acceptable salts claim 1 , polymorphs claim 1 , solvates and hydrates thereof wherein claim 1 ,{'sub': 1', '2, 'Aand Aare same or different, and independently selected from 1, 2, 3, or 4 amino acid residues wherein the amino acid residues are independently selected from L-configuration or D-configuration and are positively charged.'}4. The compound as claimed in or its stereoisomers claim 1 , pharmaceutically acceptable salts claim 1 , polymorphs claim 1 , solvates and hydrates thereof wherein claim 1 ,{'sub': '2', 'Y is —CH—;'}{'sup': '1', 'Nis positively charged.'}710-. (canceled)11. A method of treating a disease or condition in a patent claim 1 , said method comprising administering to a patient a compound of formula (I) claim 1 , as claimed in claim 1 , or its stereoisomers claim 1 , pharmaceutically acceptable salts claim 1 , polymorphs claim 1 , solvates and hydrates thereof claim 1 , wherein said disease or condition is caused by microorganism selected from the group consisting of bacteria claim 1 , ...

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Номер записи: 58
01-06-2017 дата публикации

COMPOUND, ACTIVE ENERGY RAY CURABLE COMPOSITION, CURED ARTICLE THEREOF, PRINTING INK, AND INKJET RECORDING INK

Номер: US20170152391A1
Автор: Kondou Akihiro, Miyamoto Masanori, Tanimoto Youichi, YAMADA Tomokazu, Yamamoto Sei, Yogo Azusa
Принадлежит: DIC CORPORATION

A compound obtained through Michael addition reaction of an α-aminoacetophenone skeleton-containing compound (I) represented by the following general formula (1) and a reactive compound (II) having a function as a Michael acceptor is used as a photopolymerization initiator. In the general formula (1), Rrepresents an aliphatic group, Rto Reach independently represent an aliphatic group, etc., Rto Reach independently represent a hydrogen atom, Xrepresents a single bond or a C1-6 alkylene group, Xrepresents a carbonyl group, Yand Yrepresent a group represented by the following general formula (2). However, when Yand Yboth have a structure represented by the general formula (2), Xin at least one of them is —NH—. In the general formula (2), Xand Xeach independently represent a linear or branched alkylene group having 2 to 6 carbon atoms, Xrepresents a single bond, —O— or —NH—. 2. The compound according to claim 1 , wherein the reactive compound (II) having a function as a Michael acceptor is a polyfunctional (meth)acrylate compound.3. The compound according to claim 1 , wherein (the number of the Michael addition donor function-having groups in the α-aminoacetophenone skeleton-containing compound (I) having a function as a Michael addition donor)/(the number of the Michael acceptor function-having groups in the reactive compound) is within a range of 1/20 to 1/2.7. A compound having polymerization initiation performance claim 5 , which is obtained through reaction of the compound (A) of and a compound (B) capable of reacting with the compound (A).8. The compound according to claim 7 , wherein the compound (B) having a functional group reactive with the amino group in the compound or a functional group reactive with the structural moiety represented by:{'br': None, 'sub': '2', '—X—Z,'}in the general formula (1′) is a hydroxyl group-containing (meth)acrylate compound.9. A photopolymerization initiator comprising the compound of .10. An active energy ray curable composition ...

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Номер записи: 59
08-06-2017 дата публикации

CURCUMIN ANALOGUES AS ZINC CHELATORS AND THEIR USES

Номер: US20170158605A1
Автор: Golub Lorne, Johnson Francis
Принадлежит:

This invention provides a compound having the structure 2. The compound of claim 1 , wherein when Ris H claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , or R claim 1 , is —NO claim 1 , —NRR claim 1 , —NHRR claim 1 , —SR claim 1 , —SOR claim 1 , —COR claim 1 , CF claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl; or a salt thereof.3. The compound of claim 1 , wherein when Ris H claim 1 , Ror Ris —NO claim 1 , —NRR claim 1 , —NHRR; or a salt thereof.4. The compound of claim 1 , wherein when Ris H claim 1 , Ror Ris —NRRor —NHRR; or a salt thereof.5. The compound of claim 1 , wherein{'sub': 1', '14, 'claim-text': {'sub': '14', 'wherein Ris methoxy or —NH-phenyl;'}, 'Ris H or —COR,'}{'sub': 2', '5', '6', '7', '10', '11, 'R, R, R, R, Rand Rare each H;'}{'sub': 3', '4', '8', '9', '3', '3', '2', '3', '2, 'sup': '+', 'R, R, R, and Rare each, independently H, —OH, —OCH, —N(CH)or —NH(CH);'}or a salt thereof.11. The compound of wherein Ris methoxy claim 8 , —ORor —NRR claim 8 ,{'sub': 15', '3-10', '2-10', '2-10', '16', '17', '1-10', '2-10', '2-10, 'wherein Ris H, Calkyl, Calkenyl, or Calkynyl; Rand Rare each, independently, H, Calkyl, Calkenyl, Calkynyl, aryl, heteroaryl, or heterocyclyl;'}or a salt thereof.12. The compound of wherein Ris methoxy or —NRR claim 11 ,{'sub': 16', '17', '1-10', '2-10', '2-10, 'wherein Rand Rare each, independently, H, Calkyl, Calkenyl, Calkynyl, aryl, heteroaryl, or heterocyclyl; or a salt thereof.'}13. The compound of wherein Ris —OR claim 11 , wherein Ris H claim 11 , Calkyl claim 11 , Calkenyl claim 11 , or Calkynyl; or a salt thereof.14. The compound of claim 12 , wherein{'sub': 14', '16', '17, 'claim-text': {'sub': 16', '17, 'wherein Rand Rare each, independently, H or aryl;'}, 'Ris —NRR,'}{'sub': 2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '28', '29', '28, 'claim-text': [{'sub': 28', '29', '1-10, 'wherein Rand Rare each, H or Calkyl;'}, 'or a salt thereof; or, 'R, R, R, R, R, R, R, R, R, and Rare each ...

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Номер записи: 60
24-06-2021 дата публикации

Method for treating a patient having cancer

Номер: US20210188765A1
Автор: Abdelsattar M. Omar, Azizah M. Malebari, Dhaval Shah, Farid Ahmed, Maan T. Khayat, Martin K. Safo, Moustafa E. El-Araby
Принадлежит: KING ABDULAZIZ UNIVERSITY

Therapeutic compounds containing a phenyl core and amide link(s). Also described are pharmaceutical compositions incorporating the therapeutic compounds and a method for treating cancer with the compounds. These compounds are cytotoxic to stomach, colon, breast, and leukemia cancer cell lines via dual inhibition of Src kinases and tubulin.

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Номер записи: 61
11-09-2014 дата публикации

LYSINE DEMETHYLASE INHIBITORS FOR DISEASES AND DISORDERS ASSOCIATED WITH FLAVIVIRIDAE

Номер: US20140256742A1
Автор: BAKER Jonathan A., Fyfe Matthew Collin Thor
Принадлежит:

The invention relates to methods and compositions for the treatment or prevention of Flaviviridae infections. In particular, the invention relates to an LSD1 inhibitor for use in treating or preventing Flaviviridae infections, including hepatitis C virus infections.

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Номер записи: 62
11-09-2014 дата публикации

CATHEPSIN CYSTEINE PROTEASE INHIBITORS

Номер: US20140256743A1
Автор: Baskaran Chitra I., Bayly Christopher I., Black Cameron, Gauthier Jacques Yves, Green Michael J., Hirschbein Bernard L., Janc James William, Lau Cheuk, Leger Serge, Li Chun Sing, McKay Dan, Mellon Christophe, Palmer James T., Therien Michel, Truong Vouy-Linh
Принадлежит:

This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

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Номер записи: 63
28-05-2020 дата публикации

SELF-ORIENTED MATERIAL, SELF-ORIENTED LIQUID CRYSTAL MATERIAL AND MANUFACTURING METHOD OF LIQUID CRYSTAL PANEL

Номер: US20200165518A1
Автор: Wu Ling
Принадлежит:

The invention provides a self-oriented material, a self-oriented liquid crystal material and a manufacturing method of the liquid crystal panel. The self-oriented material provided by the invention can be used for carrying out alignment on liquid crystal molecules, and a polyimide alignment layer is not required to he arranged in the liquid crystal panel when the self-oriented material is added into the liquid crystal material. The self-oriented liquid crystal material disclosed by the invention contains the self-oriented material, the self-oriented material can be used for carrying out alignment on liquid crystal molecules, therefore a polyimide alignment layer is not required to be arranged in the liquid crystal panel. According to the manufacturing method of the liquid crystal panel, the orientation of the liquid crystal molecules is realized by utilizing the self-oriented material in the self-oriented liquid crystal material, and the polyimide alignment layer does not need to be manufactured, so that the process for manufacturing the polyimide alignment layer is saved, and the production cost is reduced. 2. The self-oriented material according to claim 1 , wherein the aromatic ring comprises a benzene ring claim 1 , and the SP1 and the SP2 are the same or different; wherein the polymerizable group at the tail end of the P group comprises one of a methacrylate group claim 1 , an acrylic ester group claim 1 , a vinyl group and an ethyleneoxy group.4. A self-oriented liquid crystal material claim 1 , comprising a liquid crystal material and the self-oriented material as claimed in claim 1 , wherein the liquid crystal material comprises liquid crystal molecules.5. The self-oriented liquid crystal material according to claim 4 , wherein the mass percent of the self-oriented material in the self-oriented liquid crystal material is 0.1%-2%.6. A manufacturing method of the liquid crystal panel comprising the following steps:{'claim-ref': {'@idref': 'CLM-00004', 'claim 4 ...

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Номер записи: 64
30-06-2016 дата публикации

Beta-substituted beta-amino acids and analogs as chemotherapeutic agents

Номер: US20160185710A1
Автор: Bernd Jandeleit, Kerry J. Koller, Wolf-Nicolas Fischer
Принадлежит: QUADRIGA BIOSCIENCES Inc

β-Substituted β-amino acids, β-substituted β-amino acid derivatives, and β-substituted β-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.

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Номер записи: 65
13-06-2019 дата публикации

LAUNDRY BUILDERS AND SURFACTANTS DERIVED FROM BIO-BASED HYDROXYACIDS AND EPOXIDES

Номер: US20190177655A1
Автор: Cafmeyer Jeffrey T., Garbark Daniel B., Lalgudi Ramanathan S.
Принадлежит:

Fatty acid based surfactants and methods for producing fatty acid based surfactants are described. The method includes reacting a fatty acid ester epoxide with a hydroxy acid, a hydroxy ester, a polyoxyalkyl diol, or a polyamine. Any remaining esters from the original fatty acid ester epoxide or hydroxy ester can optionally be hydrolyzed. Methods for making citric acid derived surfactants are also described. 1. A method for producing a fatty acid based surfactant comprising:reacting a fatty acid ester epoxide with a hydroxy acid, a hydroxy ester, a polyoxyalkyl diol, or a polyamine.2. The method of further comprising hydrolyzing the ester from the fatty acid ester epoxide or the hydroxy ester under basic conditions.3. The method of wherein the fatty acid ester epoxide is reacted with the hydroxy acid or hydroxy ester and wherein the hydroxy acid or hydroxy ester is a bio-based hydroxy acid or hydroxy ester.4. The method of wherein the fatty acid ester epoxide is reacted with the hydroxy ester and wherein the hydroxy ester contains an alkyl group having 1 to 20 carbon atoms.5. The method of wherein the fatty acid ester epoxide is reacted with the hydroxy acid or hydroxy ester and wherein the hydroxy acid comprises one or more of citric acid claim 1 , malic acid claim 1 , lactic acid claim 1 , glycolic acid claim 1 , or tartaric acid claim 1 , or wherein the hydroxy ester comprises one or more of triethyl citrate claim 1 , trimethyl citrate claim 1 , diethyl malate claim 1 , dimethyl malate claim 1 , ethyl lactate claim 1 , methyl lactate claim 1 , ethyl glycolate claim 1 , methyl glycolate claim 1 , ethyl tartrate claim 1 , or methyl tartrate.6. The method of wherein the fatty acid ester epoxide is reacted with the polyoxyalkyl diol and wherein the polyoxyalkyl diol comprises one or more of diethylene glycol claim 1 , triethylene glycol claim 1 , poly(ethylene glycol) claim 1 , dipropylene glycol claim 1 , tripropylene glycol claim 1 , or poly(propylene glycol).7. ...

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Номер записи: 66
20-06-2019 дата публикации

Novel antibiotics

Номер: US20190185417A1
Автор: Ramiz Boulos
Принадлежит: Boulos & Cooper Pharmaceuticals Pty Ltd

Novel aryl compounds or pharmaceutically acceptable salts thereof, and uses of the same for the treatment of Gram-negative infections.

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Номер записи: 67
25-09-2014 дата публикации

SUBSTITUTED BENZYLAMINE COMPOUNDS, THEIR USE IN MEDICINE, AND IN PARTICULAR THE TREATMENT OF HEPATITIS C VIRUS (HCV) INFECTION

Номер: US20140288040A1
Автор: "OBrien Michael Alistair", Besong Gilbert Ebai, CARR Maria Grazia, Chessari Gianni, HISCOCK Steven Douglas, Rees David Charles, Saalau-Bethell Susanne Maria, Thompson Neil Thomas, WILLEMS Hendrika Maria Gerarda, WOODHEAD Andrew James
Принадлежит: ASTEX THERAPEUTICS LIMITED

The invention provides compounds of the formula (6): 2. A compound according to claim 1 , or a salt claim 1 , N-oxide or tautomer thereof claim 1 , wherein A is CH and E is CH.3. A compound according to claim 1 , or a salt claim 1 , N-oxide or tautomer thereof claim 1 , wherein Ris hydrogen.4. A compound according to claim 1 , or a salt claim 1 , N-oxide or tautomer thereof claim 1 , wherein Ris selected from:{'sub': 1-8', '1-8, 'sup': '6', 'an acyclic Chydrocarbon group optionally substituted with one substituent R, wherein one carbon atom of the acyclic Chydrocarbon group may optionally be replaced by a heteroatom O; and'}{'sup': '7a', 'a monocyclic carbocyclic or heterocyclic group of 3, 4, 5 or 6 ring members, of which 0, 1 or 2 are heteroatom ring members selected from O and N, the carbocyclic or heterocyclic group being optionally substituted with one or two substituents R.'}5. A compound according to claim 4 , or a salt claim 4 , N-oxide or tautomer thereof claim 4 , wherein Ris ethyl.6. A compound according to claim 1 , or a salt claim 1 , N-oxide or tautomer thereof claim 1 , wherein Ris selected from hydrogen and a group Rwherein Ris selected from a Calkyl group optionally substituted with a substituent R; cyclohexyl substituted with a substituent R; pyridine optionally substituted with a substituent R; and tetrahydroisoquinoline; wherein the substituent Ris selected from hydroxy; C(═O)NRR; piperidine; pyrrole and imidazole.7. A compound according to claim 6 , or a salt claim 6 , N-oxide or tautomer thereof claim 6 , wherein Ris a group Rwherein Ris a Calkyl group optionally substituted with a substituent R; wherein the substituent Ris selected from hydroxy and C(═O)NRR.8. A compound according to claim 6 , or a salt claim 6 , N-oxide or tautomer thereof claim 6 , wherein Ris hydrogen.9. A compound according to claim 1 , or a salt claim 1 , N-oxide or tautomer thereof claim 1 , wherein Ris fluorine.10. A compound according to claim 1 , or a salt claim 1 , N ...

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Номер записи: 68
02-10-2014 дата публикации

THE USE OF (2R, 6R)-HYDROXYNORKETAMINE, (S)-DEHYDRONORKETAMINE AND OTHER STEREOISOMERIC DEHYDRO AND HYDROXYLATED METABOLITES OF (R,S)- KETAMINE IN THE TREATMENT OF DEPRESSION AND NEUROPATHIC PAIN

Номер: US20140296241A1
Автор: BERNIER Michel, GOLDBERG MICHAEL E., Moaddel Ruin, TANGA MARY J., TORJMAN MARC C., Wainer Irving W., Zarate Carlos A.
Принадлежит:

The disclosure provides pharmaceutical preparations containing (2R,6R)-hydroxynorketamine, or (R)- or (S)-dehydronorketamine, or other stereoisomeric dehydro or hydroxylated ketamine metabolite. (2R,6R)-hydroxynorketamine The disclosure also provides novel ketamine metabolite prodrugs. The disclosure provides methods of treating, bipolar depression, major depressive disorder, neuropathic and chronic pain, including complex regional pain disorder (CRPS) by administering a purified ketamine metabolite or a ketamine metabolite prodrug directly to patients in need of such treatment. 57-. (canceled)11. A compound or salt of claim 9 , wherein{'sub': '1', 'Ris hydrogen or hydroxyl;'}{'sub': '3', 'Ris hydrogen or methyl;'}{'sub': 4', '5', '1', '2', '1', '2, 'Rand Rare each 0 to 2 substituents independently chosen from halogen, hydroxyl, amino, C-Calkyl, and C-Calkyl; and'}{'sub': '6', 'Ris hydrogen or methyl.'}12. A compound or salt of claim 11 , wherein{'sub': 2', '2', '2', '2', '2', '6', '6', '2', '1', '6', '2', '4', '0', '2', '3', '7', '0', '4', '0', '2', '0', '2', '2', '1', '4', '1', '4', '1', '6', '1', '4', '1', '2', '1', '2, 'Ris -ABwhere Ais a bond, —(C═O)O—, —S(O)—, —(S═O)NR—, or —(C═O)NR—, Bis C-Calkyl, C-Calkanoyl, (phenyl)C-Calkyl, (C-Ccycloalkyl)C-Calkyl, (heterocycloalkyl)C-Calkyl, (5- or 6-membered heteroaryl)C-Calkyl, or an amino acid covalently bound to Aby its C-terminus, each of which is substituted with from 0 to 4 substituents independently chosen from halogen, hydroxyl, amino, cyano, C-Calkyl, C-Calkoxy, C-Calkylester, mono- and di-(C-Calkyl)amino, C-Chaloalkyl, and C-Chaloalkoxy.'}1314-. (canceled)15. A compound or salt of claim 11 , where{'sub': 2', '2', '2', '6', '0', '2', '3', '7', '0', '4', '1', '4', '1', '4', '1', '4, 'Ais a bond or —(C═O)O— and Bis C-Calkyl, (phenyl)C-Calkyl, or (C-Calkyl)C-Calkyl, each of which is substituted with from 0 to 4 substituents independently chosen from halogen, hydroxyl, amino, cyano, C-Calkyl, C-Calkoxy, and mono- ...

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Номер записи: 69
28-07-2016 дата публикации

SUBSTITUTED NAPHTHALENE COMPOUNDS AS CALCIUM SENSING RECEPTOR MODULATORS

Номер: US20160214924A1
Автор: Gudade Ganesh Bhausaheb, Kamboj Rajender Kumar, Kulkarni Sanjeev Anant, Nair Prathap Sreedharan, PALLE Venkata P., Pawar Chetan Sanjay, Tryambake Mahadeo Bhaskar
Принадлежит:

The invention relates to naphthalene compounds of Formula (I) and their pharmaceutically acceptable salts, wherein the substituents are as described herein, and their use in medicine for the treatment of diseases, disorders associated with the modulation of calcium sensing receptor modulators (Ca SR). The invention also relates to pharmaceutical compositions containing such compounds in treating diseases disorders associated with calcium sensing receptor modulators (Ca SR) channel modulators. 6. The compound of claim 1 , wherein Ris independently selected from halogen claim 1 , substituted or unsubstituted (C-C)alkyl and substituted or unsubstituted (C-C)haloalkyl and —ORwhere Ris (C-C)alkyl or (C-C)haloalkyl; and ‘p’ is 0 claim 1 , 1 or 2.7. The compound of wherein Ris hydrogen or substituted or unsubstituted (C-C)alkyl.8. The compound of claim 7 , wherein (C-C)alkyl is methyl or ethyl.10. The compound of claim 1 ,wherein,{'sub': 1', '1', '3, 'Ris (C-C)alkyl;'}{'sub': 2', '1', '4', '1', '4', '1', '4', '1', '4, 'Rwhich may be same or different at each occurrence, is independently selected from halogen, (C-C)alkyl, (C-C)haloalkyl, —X—C(O)—Z, —O—(C-C)alkyl or —O—(C-C)haloalkyl;'}{'sub': a', 'b', 'm', 'a', 'b', '1', '6, 'X is selected from a bond or —(CRR)where Rand Rare independently hydrogen or substituted or unsubstituted (C-C)alkyl;'}Z is —OH;{'sub': '3', 'Ris hydrogen;'}{'sub': 4', '9, 'R, which may be same or different at each occurrence, is independently selected from halogen and —OR;'}{'sub': 9', '1', '4', '1', '4, 'Ris (C-C)alkyl or (C-C)haloalkyl;'}{'sub': 5', '1', '3, 'Ris (C-C)alkyl;'}‘m’ is an integer selected from 1 or 2;‘n’ is 1;‘p’ is 0, 1 or 2; and‘q’ is an integer ranging from 1 to 3, both inclusive;or a pharmaceutically acceptable salt thereof.11. The compound of which is selected from:(R)-1-(Naphthalen-1-yl)-N-((4-(4-(trifluoromethyl)phenyl)naphthalen-2-yl)methyl)ethanamine hydrochloride;(R)-1-(4-Fluoro-3-methoxyphenyl)-N-((4-(4-(trifluoromethyl) ...

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Номер записи: 70
27-07-2017 дата публикации

Lysine demethylase inhibitors for myeloproliferative or lymphoproliferative diseases or disorders

Номер: US20170209432A1
Автор: Iñigo TIRAPU FERNANDEZ DE LA CUESTA, Marc Martinell Pedemonte, Matthew Colin Thor Fyfe, Tamara Maes
Принадлежит: Oryzon Genomics SA

The present invention relates to methods and compositions for the treatment or prevention of diseases and disorder associated with myeloproliferative and lymphoproliferative disorders. In particular, the invention relates to an LSD1 inhibitor for use in treating or preventing diseases and disorder associated with myeloproliferative and lymphoproliferative disorders.

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Номер записи: 71
05-08-2021 дата публикации

COMPOSITION AND METHODS OF USE OF NOVEL PHENYLALANINE SMALL ORGANIC COMPOUNDS TO DIRECTLY MODULATE PCSK9 PROTEIN ACTIVITY

Номер: US20210236481A1
Автор: Barta Thomas E., Bourne Jonathan William, Bowers Simeon, Monroe Kyle D., Muehlemann Michael M., Pandey Anjali
Принадлежит:

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels. 112.-. (canceled)14. The method of claim 13 , further comprising administering to the mammal a second active pharmaceutical.15. The method of claim 13 , comprising administering a pharmaceutical composition comprising the compound of Formula I and a pharmaceutically acceptable carrier or excipient.16. The method of claim 15 , wherein said pharmaceutical composition further comprises a second active ingredient.19. The method of claim 18 , further comprising administering to the mammal a second active pharmaceutical.20. The method of claim 18 , comprising administering a pharmaceutical composition comprising the compound of Formula I and a pharmaceutically acceptable carrier or excipient.21. The method of claim 20 , wherein said pharmaceutical composition further comprises a second active ingredient.22. The method of claim 21 , wherein said second active ingredient is selected from the group consisting of a statin claim 21 , a cardiovascular drug claim 21 , a metabolic drug claim 21 , and an antihypertensive drug.25. The method of claim 24 , further comprising administering to the mammal a ...

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Номер записи: 72
26-07-2018 дата публикации

INDENYL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND MEDICAL USES THEREOF

Номер: US20180208573A1
Автор: Boyd Michael R., Chen Xi, KEETON Adam B., Piazza Gary A.
Принадлежит:

Disclosed are compounds, for example, compounds of formula (I), (Formula (I) wherein R, R, R-R, n, X, Y, Y′, and E are as described herein, pharmaceutical compositions containing such compounds, and methods of treating or preventing a disease or condition, for example, cancer. 117-. (canceled)19. The compound or salt of claim 18 , wherein Ris a substituted or unsubstituted group selected from phosphonooxy claim 18 , phosphonooxyalkyloxy claim 18 , alkyloxy claim 18 , formyloxy claim 18 , alkylcarbonyloxy claim 18 , alkylcarbonyloxyalkyloxy claim 18 , aminocarbonyloxyalkyloxy claim 18 , alkylsulfinyloxy claim 18 , alkylsulfonyloxy claim 18 , carbamate claim 18 , carbamido claim 18 , arylcarbonyloxy claim 18 , arylalkylcarbonyloxy claim 18 , aryloxycarbonyloxy claim 18 , heterocyclylcarbonyloxy and heterocyclylalkylcarbonyloxy.20. The compound or salt of claim 19 , wherein Ris a substituted or unsubstituted group selected from from aminocarbonyloxyalkyloxy claim 19 , dimethylaminocarbonyloxy claim 19 , dimethylaminocarbonyloxyalkyloxy claim 19 , piperidinylcarbonyloxy claim 19 , piperidinylcarbonyloxyalkyloxy claim 19 , dipiperidinylcarbonyloxy claim 19 , and dipiperidinylcarbonyloxyalkyloxy.21. The compound or salt of claim 18 , wherein R is selected from heterocyclyl and heterocyclylalkyl claim 18 , wherein the cyclic structure of heterocyclyl and heterocyclylalkyl is selected from furanyl claim 18 , pyrrolyl claim 18 , thiophenyl claim 18 , and imidazolyl claim 18 , and said cyclic structure is optionally substituted with one or more of halo claim 18 , alkyl claim 18 , haloalkyl claim 18 , hydroxy claim 18 , alkoxy claim 18 , amino claim 18 , alkylamino claim 18 , dialkylamino claim 18 , mercapto claim 18 , alkylmercapto claim 18 , and carboxamido.22. The compound or salt of claim 21 , wherein R′ is selected from heterocyclyl and heterocyclylalkyl claim 21 , wherein the cyclic structure of heterocyclyl and heterocyclylalkyl is selected from furanyl and pyrrolyl ...

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Номер записи: 73
26-07-2018 дата публикации

Lmp7 inhibitors

Номер: US20180208589A1
Автор: Kenneth Albert Brameld, Timothy Owens
Принадлежит: Principia Biopharma Inc

The present disclosure provides compounds that are Large Multifunctional Protease 7 (LMP7) inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of LMP7. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

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Номер записи: 74
25-06-2020 дата публикации

Functional derivative compounds of alanine and proline amino acids and pharmaceutical composition comprising same

Номер: US20200199065A1
Автор: Ae Nim Pae, Bo Ko JANG, Ji Won Choi, Jong Hyun Park, Jong-Seung Lee, Ki Duk Park, Kyung-Tae Lee, Seul Ki YEON, Siwon KIM, Yong Koo Kang, Yong-Sun Bahn
Принадлежит: Amtixbio Co Ltd

The present invention relates to novel functional derivatives of alanine and proline amino acids. The compounds of the present invention were confirmed to have a very superior antifungal or fungicidal effect. In addition, the compounds of the present invention were confirmed to exhibit a synergistic effect when co-administered with an existing antifungal preparation. Moreover, the compounds of the present invention showed activity on a wide range of fungi. Therefore, the compounds of the present invention can be widely used in a field which requires the treatment with an antifungal or fungicidal preparation against human infectious fungi, animal infectious fungi, and phytopathogenic fungi.

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Номер записи: 75
02-08-2018 дата публикации

Antibacterials and/or modulators of biofilm formation and methods of using the same

Номер: US20180215704A1
Автор: Jack Geno Samaritoni, Martin J. O'donnell, William L. Scott
Принадлежит: Indiana University Research And Technology Corp

Amides substituted with aromatic groups were synthesized and some were purified to create enantiomer pure compounds. The compounds were tested to determine their ability to inhibit the growth of bacteria and the formation of biofilms created by bacteria. Some of these compounds were found to be effective antibacterials and to effectively inhibit the formation of biofilms.

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Номер записи: 76
16-10-2014 дата публикации

NOVEL PYRROLE DERIVATIVES

Номер: US20140309193A1
Автор: Andrew Peter William, Damaso Mafalda Pires, Davies Mark William, Frickel Fritz-Frieder, Hamza Daniel, Hirst Simon Christopher, Lonnen Rana
Принадлежит:

There are provided inter alia compounds of formula (I) wherein R, R, R, Rand Rare as defined in the specification and their use in therapy, especially in the treatment of bacterial (e.g. pneumococcal) infections. 2. A compound according to wherein Rand Rare independently selected from —C(O)NRR claim 1 , —C(O)OR claim 1 , CN claim 1 , —C(O)R claim 1 , —C(O)NHC(O)R claim 1 , —NO claim 1 , —SOR claim 1 , —SOR claim 1 , —SOR claim 1 , —SONRR claim 1 , —SONH—C(O)ORand optionally substituted phenyl or heteroaryl.3. A compound according to wherein Rand Rare independently selected from —C(O)NRR claim 2 , —C(O)ORand CN.4. A compound according to wherein Rand Rare independently selected from —C(O)NRRand —C(O)OR.5. A compound according to wherein (i) Ris —C(O)NRRand Ris —C(O)NRRor (ii) Ris —C(O)NRRand Ris —C(O)OR.6. A compound according to wherein Ris —C(O)ORand Ris —C(O)OR.7. A compound according to wherein Ris substituted phenyl.8. A compound according to wherein Ris phenyl substituted by one or more substituents independently selected from halo claim 7 , cyano claim 7 , hydroxyl claim 7 , C-Calkoxy claim 7 , C-Chydroxyalkoxy claim 7 , C-Cfluoroalkoxy claim 7 , C-Calkyl claim 7 , C-Cfluoroalkyl claim 7 , —C(O)NRR claim 7 , where Rand Rare independently selected from hydrogen and C-Calkyl; —O—Rwherein Ris —(CH)—P(O)(OR) claim 7 , where x is 0 claim 7 , 1 claim 7 , 2 claim 7 , 3 or 4 and Ris independently selected from hydrogen and C-Calkyl claim 7 , —(CH)—S(O)Me where y is 1 claim 7 , 2 claim 7 , 3 or 4 claim 7 , —C-Calkylheterocyclyl which heterocyclyl group may be optionally substituted by C-Calkyl claim 7 , —C-Calkylphenyl which phenyl group may be optionally substituted by C-Calkoxy claim 7 , or phenyl or 5- or 6-membered heteroaryl which phenyl or heteroaryl group may optionally be substituted by a group selected from C-Calkyl and halo; or —(O(CH))OR claim 7 , where each z claim 7 , which may be the same or different claim 7 , represents 2 or 3 claim 7 , p represents 1 ...

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Номер записи: 77
20-08-2015 дата публикации

LYSINE DEMETHYLASE INHIBITORS FOR MYELOPROLIFERATIVE DISORDERS

Номер: US20150232436A1
Автор: Baker Jonathan Alleman, Castro Palomino Julio, Fyfe Matthew Colin Thor, Maes Tamara, MARTINELL PEDEMONTE Marc
Принадлежит:

The invention relates to methods and compositions for the treatment or prevention of diseases and disorders associated with myeloproliferative disorders. In particular, the invention relates to an LSD 1 inhibitor for use in treating or preventing Philadelphia chromosome negative myeloproliferative disorders. 14-. (canceled)5. A method of treating or preventing a Philadelphia chromosome negative myeloproliferative disease or disorder comprising administering to an individual a therapeutically effective amount of a LSD1 inhibitor.6. A method of treating or preventing a symptom of a Philadelphia chromosome negative myeloproliferative disease or disorder comprising administering to an individual a therapeutically effective amount of a LSD1 inhibitor.7. The method of wherein said Philadelphia chromosome negative myeloproliferative disease or disorder is essential thrombocythemia claim 5 , polycythemia vera or myelofibrosis.810-. (canceled)11. The method of wherein said LSD1 inhibitor is a small molecule inhibitor of LSD1.12. The method of wherein said LSD1 inhibitor is a selective LSD1 inhibitor.13. (canceled)14. The method of wherein said LSD1 inhibitor is an irreversible or a reversible amine oxidase inhibitor.15. The method of wherein said LSD1 inhibitor is a 2-cyclylcyclopropan-1-amine compound claim 5 , a phenelzine compound or a propargylamine compound.16. The method of wherein said LSD1 inhibitor is a 2-arylcyclopropan-1-amine compound or a 2-heteroarylcyclopropan-1-amine compound.1718-. (canceled)20. The method of wherein Ris —H.21. The method of wherein A is aryl or heteroaryl and wherein A is unsubstituted or has 1 or 2 substituents A′.22. (canceled)23. The the method of wherein A is phenyl claim 21 , pyridinyl claim 21 , pyrimindinyl claim 21 , thiophenyl claim 21 , benzothiophenyl claim 21 , pyrroyl claim 21 , indolyl claim 21 , furanyl claim 21 , or thiazolyl claim 21 , and wherein A is unsubstituted or has 1 or 2 substituents A′.2432-. (canceled)33. The ...

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Номер записи: 78
23-10-2014 дата публикации

N-PHENYL ANTHRANILIC ACID DERIVATIVES AND USES THEREOF

Номер: US20140316008A1
Автор: ATTALI Bernard, PERETZ Asher
Принадлежит:

Compounds that can be used as openers or blockers of voltage-dependent potassium channels, and which are useful in the treatment of conditions such as central or peripheral nervous system disorders through the modulation of potassium ion flux through voltage-dependent potassium channels and/or depressing or enhancing cortical and/or peripheral neuron activity, compositions containing same and methods utilizing same are disclosed. Also disclosed are modulators of voltage-dependent potassium channels, which exhibit blocking of a TRPV1 channel, and hence are useful in the treatment of TRPV1-related conditions. 2. The method of claim 1 , wherein Y is selected from the group consisting of hydroxyalkyl and a polyalkylene glycol moiety.3. The method of claim 1 , wherein:G is C;K is O;{'sup': 2', '3', '4', '5', '6, 'each of R, R, R, Rand Ris independently selected from the group consisting of hydrogen, alkyl, halo and trihaloalkyl; and'}{'sup': 7', '8', '9', '10, 'each of R, R, Rand Ris hydrogen.'}4. The method of claim 1 , wherein at least one of said R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Ris an electron-withdrawing group.5. The method of claim 4 , wherein at least one of R claim 4 , R claim 4 , Rand Ris said electron-withdrawing group.6. The method of claim 5 , wherein at least one of R claim 5 , R claim 5 , Rand Ris an electron-withdrawing group and at least one of R claim 5 , R claim 5 , R claim 5 , Rand Ris an electron withdrawing group.7. The method of claim 4 , wherein Ris said electron-withdrawing group.9. The method of claim 1 , wherein said compound does not modulate TRPV6.10. The method of claim 1 , wherein blocking said TRPV1 is for the treatment of a TRPV1 related disorder selected from the group consisting of epilepsy claim 1 , pain related conditions such as neurogenic pain claim 1 , neuropathic pain claim 1 , allodynia claim 1 , pain associated with inflammation claim 1 , bipolar disorder claim 1 , mood ...

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Номер записи: 79
16-07-2020 дата публикации

INDENYL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND MEDICAL USES THEREOF

Номер: US20200223815A1
Автор: Boyd Michael R., Chen Xi, KEETON Adam B., Piazza Gary A.
Принадлежит: ADT PHARMACEUTICALS, LLC

Disclosed are compounds, for example, compounds of formula I, 137-. (canceled)39. The method of claim 38 , wherein the patient's cancer is a cancer selected from pancreatic cancer claim 38 , lung cancer claim 38 , colorectal cancer claim 38 , melanoma claim 38 , ovarian cancer claim 38 , renal cancer claim 38 , prostate cancer claim 38 , head and neck cancer claim 38 , endocrine cancer claim 38 , uterine cancer claim 38 , breast cancer claim 38 , sarcoma cancer claim 38 , gastric cancer claim 38 , hepatic cancer claim 38 , esophageal cancer claim 38 , central nervous system cancer claim 38 , brain cancer claim 38 , hepatic cancer claim 38 , germline cancer claim 38 , lymphoma claim 38 , and leukemia.40. The method of claim 39 , wherein the cancer is selected from pancreatic cancer claim 39 , colorectal cancer claim 39 , and lung cancer.41. The method of claim 39 , wherein the patient's cancer contains an activating mutation of a ras gene and/or a hyperactive Ras protein.43. The method of claim 42 , wherein the patient's cancer is a cancer selected from pancreatic cancer claim 42 , lung cancer claim 42 , colorectal cancer claim 42 , melanoma claim 42 , ovarian cancer claim 42 , renal cancer claim 42 , prostate cancer claim 42 , head and neck cancer claim 42 , endocrine cancer claim 42 , uterine cancer claim 42 , breast cancer claim 42 , sarcoma cancer claim 42 , gastric cancer claim 42 , hepatic cancer claim 42 , esophageal cancer claim 42 , central nervous system cancer claim 42 , brain cancer claim 42 , hepatic cancer claim 42 , germline cancer claim 42 , lymphoma claim 42 , and leukemia.44. The method of claim 43 , wherein the cancer is selected from pancreatic cancer claim 43 , colorectal cancer claim 43 , and lung cancer.45. The method of claim 43 , wherein the patient's cancer contains an activating mutation of a ras gene and/or a hyperactive Ras protein.47. The method of claim 46 , wherein the patient's cancer is a cancer selected from pancreatic cancer claim ...

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Номер записи: 80
16-07-2020 дата публикации

Indenyl compounds, pharmaceutical compositions, and medical uses thereof

Номер: US20200223816A1
Автор: Adam B. Keeton, Gary A. Piazza, Michael R. Boyd, Xi Chen
Принадлежит: ADT Pharmaceuticals LLC

wherein R, R0, R1-R8, n, X, Y, Y′, and E are as described herein, pharmaceutical compositions containing such compounds, and methods of treating or preventing a disease or condition, for example, cancer.

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Номер записи: 81
16-07-2020 дата публикации

METHOD OF TREATING OR PREVENTING RAS-MEDIATED DISEASES

Номер: US20200223817A1
Автор: Boyd Michael R., Chen Xi, KEETON Adam B., Piazza Gary A.
Принадлежит: ADT PHARMACEUTICALS, LLC

Disclosed are compounds, for example, a compound of formula I, 119-. (canceled)21. The method of claim 20 , wherein the prodrug is selected from:(Z)-2-(5-fluoro-2-methyl- 1-(3,4,5-trimethoxybenzylidene)-1H-inden-3-yl)-N-phenylacetamide,(Z)-2-(5-methoxy-2-methyl-1-(3,4,5-trimethoxybenzylidene)-1H-inden-3-yl)-N-phenylacetamide,(Z)—N-benzyl-2-(5-fluoro-2-methyl- 1-(3,4,5-trimethoxybenzylidene)-1H-inden-3-yl)acetamide, and(Z)—N-benzyl-2-(5-methoxy-2-methyl-1-(3,4,5-trimethoxybenzylidene)-1H-inden-3-yl)acetamide,or a pharmaceutically acceptable salt thereof.22. The method of claim 21 , wherein the prodrug is:(Z)-2-(5-fluoro-2-methyl-1-(3,4,5-trimethoxybenzylidene)-1H-inden-3-yl)-N-phenylacetamide.23. The method of claim 21 , wherein the prodrug is:(Z)-2-(5-methoxy-2-methyl-1-(3,4,5-trimethoxybenzylidene)-1H-inden-3-yl)-N-phenylacetamide.24. The method of claim 21 , wherein the prodrug is:(Z)—N-benzyl-2-(5-fluoro-2-methyl- 1-(3,4,5-trimethoxybenzylidene)-1H-inden-3-yl)acetamide.25. The method of claim 21 , wherein the prodrug is:(Z)—N-benzyl-2-(5-methoxy-2-methyl- 1-(3,4,5-trimethoxybenzylidene)-1H-inden-3-yl)acetamide. This application is a continuation of co-pending U.S. patent application Ser. No. 15/537,283, filed Jun. 16, 2017, as the US national phase of PCT/US2015/066154, filed Dec. 16, 2015, claiming the benefit of U.S. patent application Ser. No. 14/571,690, filed Dec. 16, 2014, the disclosures of all of which are incorporated by reference in their entireties for all purposes.This invention was made with partial support under NIH/NCI Grant Numbers CA 155638 and CA 148817. Therefore, the U.S. Government has certain rights in this invention.Cancer is a leading cause of death in the developed world, with over one million people diagnosed and more than 500,000 deaths per year in the United States alone. Overall it is estimated that at least one in three people will develop some form of cancer during their lifetime. There are more than 200 different histopathological ...

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Номер записи: 82
16-07-2020 дата публикации

SYNTHESIS OF POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS

Номер: US20200223866A1
Автор: Chiu Anna, Enquist, Griggs Nolan, Hale Christopher, Ikemoto Norihiro, JR. John, Keaton Katie Ann, Kraft Matt, Lazerwith Scott E., Leeman Michel, Peng Zhihui, Schrier Kate, Trinidad Jonathan, Van Herpt Jochem, Waltman Andrew W.
Принадлежит:

Methods of making compounds of Formula I are disclosed: 1153-. (canceled)155. The process of wherein B-1.J-1 is reacted in the presence of an acid.156. The process of wherein the acid is selected from the group consisting of an inorganic acid claim 155 , an organic acid claim 155 , a halogenated organic acid claim 155 , a Lewis acid and mixtures thereof.157. The process of wherein the acid is selected from the group consisting of hydrochloric acid claim 156 , hydrobromic acid claim 156 , hydroiodic acid claim 156 , trifluoromethanesulfonic acid claim 156 , formic acid claim 156 , trifluoroacetic acid claim 156 , trichloroacetic acid claim 156 , perfluoropropionic acid claim 156 , dichloroacetic acid claim 156 , chloroacetic acid claim 156 , acetic acid claim 156 , para-toluenesulfonic acid claim 156 , methane sulfonic acid claim 156 , zinc chloride claim 156 , magnesium bromide claim 156 , magnesium triflate claim 156 , copper triflate claim 156 , scandium triflate claim 156 , and a mixture thereof.158. The process of wherein the acid is trifluoroacetic acid.159. The process of wherein the alkylated formamide acetal is selected from the group consisting of N claim 154 ,N-dimethylformamide dimethyl acetal claim 154 , N claim 154 ,N-dimethylformamide diethyl acetal claim 154 , N claim 154 ,N-dimethylformamide diisopropyl acetal claim 154 , N claim 154 ,N-diethylformamide dimethyl acetal claim 154 , and N claim 154 ,N-diisopropylformamide dimethyl acetal.160. The process of wherein the alkylated formamide acetal is N claim 159 ,N-dimethylformamide dimethyl acetal.161. The process of wherein C-1 is reacted with an alkylated formamide acetal in the presence of an acid.162. The process of wherein the acid is selected from the group consisting of trifluoroacetic acid claim 161 , formic acid claim 161 , acetic acid claim 161 , sulfuric acid trifluoroacetic acid claim 161 , trichloroacetic acid claim 161 , and perfluoropropionic acid.163. The process of claim 162 , wherein ...

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Номер записи: 83
23-08-2018 дата публикации

COMPOSITION AND METHODS OF USE OF NOVEL PHENYLALANINE SMALL ORGANIC COMPOUNDS TO DIRECTLY MODULATE PCSK9 PROTEIN ACTIVITY

Номер: US20180237381A1
Автор: Barta Thomas E., Bourne Jonathan William, Bowers Simeon, Monroe Kyle D., Muehlemann Michael M., Pandey Anjali
Принадлежит:

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels. 2. The compound of claim 1 , formulated as a pharmaceutical composition.3. The compound of claim 2 , wherein said pharmaceutical composition further comprises a pharmaceutical drug.4. The compound of claim 3 , wherein said pharmaceutical drug is selected from the group consisting of a statin claim 3 , a cardiovascular drug claim 3 , a metabolic drug claim 3 , and an antihypertensive drug.5. A method claim 3 , comprising: i) a PCSK9 protein, wherein said protein comprises a binding site that induces allosteric modulation and a low density lipoprotein receptor binding site;', 'ii) a small organic compound capable of binding to said binding site, and selected from the group consisting of a compound of a phenylalanine scaffold of Formula I; and', 'iii) a plurality of hepatocyte cells comprising a low density lipoprotein receptor and low density lipoproteins;, 'a) providing;'}b) binding said small organic compound to said binding site, wherein said small organic compound induces a conformational shift of said protein; andc) modulating the rate of low density lipoprotein receptor ...

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Номер записи: 84
24-08-2017 дата публикации

UV-ABSORBING VINYLIC MONOMERS AND USES THEREOF

Номер: US20170242275A1
Автор: Chang Frank, DeSousa Ryan, Holland Troy Vernon, Nelson Jared, Pruitt John Dallas
Принадлежит:

Described herein are water-soluble UV-absorbing vinylic monomers and their uses in preparing UV-absorbing contact lenses capable of blocking ultra-violet (“UV”) radiation and optionally (but preferably) violet radiation with wavelengths from 380 nm to 440 nm, thereby protecting eyes to some extent from damages caused by UV radiation and potentially from violet radiation. This invention also provides a UV-absorbing contact lens. 2. The UV-absorbing vinylic monomer of claim 1 , being a vinylic monomer of formula (I).4. The UV-absorbing vinylic monomer of claim 1 , being a vinylic monomer of formula (II).6. The UV-absorbing vinylic monomer of claim 1 , being a vinylic monomer of formula (III).8. The UV-absorbing vinylic monomer of claim 1 , being a vinylic monomer of formula (IV) or (V).10. The UV-absorbing vinylic monomer of claim 1 , being a vinylic monomer of formula (VI) or (VII).12. A hydrogel contact lens claim 1 , comprising a crosslinked polymeric material which comprises repeating units of a UV-absorbing vinylic monomer of claim 1 , wherein the hydrogel contact lens has: an UVB transmittance (designated as UVB % T) of about 10% or less between 280 and 315 nanometers; an UVA transmittance (designated as UVA % T) of about 30% or less between 315 and 380 nanometers; optionally a Violet transmittance (designated as Violet % T) of about 60% or less between 380 nm and 440 nm; and a water content of from about 15% to about 80% by weight (at room temperature claim 1 , about 22° C. to 28° C.) when being fully hydrated.13. The hydrogel contact lens of claim 12 , wherein the hydrogel contact lens is a silicone hydrogel contact lens claim 12 , wherein the crosslinked polymeric material which comprises repeating units of at least one hydrophilic vinylic monomer and repeating units of at least one siloxane-containing vinylic monomer and/or macromer.14. The hydrogel contact lens of claim 12 , wherein the crosslinked polymeric material which comprises repeating units of an ...

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Номер записи: 85
30-08-2018 дата публикации

PROCESSES FOR THE PREPARATION OF IVACAFTOR

Номер: US20180244622A1
Автор: CHAVA Satyanarayana, Dammalapati Venkata Lakshmi Narasimha Rao, Reddy Venkata Krishna, Thatipally Suresh
Принадлежит: Laurus Labs Ltd.

The present invention provides processes for the preparation of ivacaftor using novel intermediates and a process for its preparation. 2. The process of claim 1 , wherein the cleavable group is selected from the group consisting of tertiary butyloxy carbonyl claim 1 , carboxy benzoyl claim 1 , fluorenylmethyloxycarbonyl claim 1 , allyloxycarbonyl claim 1 , a methyl carbamate claim 1 , an ethyl carbamate claim 1 , phthalimide claim 1 , formyl claim 1 , acetyl claim 1 , pivaloyl claim 1 , trityl claim 1 , benzyl claim 1 , benzoyl claim 1 , p-nitrobenzoyl claim 1 , p-phenyl benzyl claim 1 , 4-methoxy benzyl claim 1 , 4-trifluoromethyl benzyl claim 1 , 4-chloro benzyl claim 1 , trimethylsilyl claim 1 , tert-butyldiphenylsilyl claim 1 , tert-butyldimethylsilyl claim 1 , and triisopropylsilyl.3. The process of claim 1 , wherein the leaving group is selected from the group consisting of chloro claim 1 , bromo claim 1 , iodo claim 1 , mesyl claim 1 , tosyl claim 1 , triflate and nosyl.4. The process of claim 1 , wherein ‘R’ represents hydrogen or benzyl and ‘X’ is chloro.5. The process of claim 1 , wherein the step a) is carried out in presence of a base and a solvent.6. The process of claim 5 , wherein the solvent is selected from the group consisting of tetrahydrofuran claim 5 , 2-methyl tetrahydrofuran claim 5 , dimethyl ether claim 5 , diisopropyl ether claim 5 , methyl tertiary butyl ether claim 5 , 1 claim 5 ,4-dioxane claim 5 , methylene chloride claim 5 , ethylene chloride claim 5 , chloroform claim 5 , toluene claim 5 , xylene claim 5 , dimethylformamide claim 5 , dimethyl acetamide claim 5 , N-methyl pyrrolidinone claim 5 , dimethylsulfoxide claim 5 , sulfolane claim 5 , acetonitrile claim 5 , propionitrile claim 5 , and mixtures thereof.7. The process of claim 5 , wherein the base is selected from the group consisting of sodium hydroxide claim 5 , potassium hydroxide claim 5 , sodium methoxide claim 5 , sodium ethoxide claim 5 , sodium-tert-butoxide claim 5 , ...

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Номер записи: 86
08-08-2019 дата публикации

Novel Myocyte Enhancer Factor 2 (MEF2) modulators

Номер: US20190241504A1
Автор: Zhang Junhu
Принадлежит:

The present disclosure provides novel compounds capable of functioning as Myoctye Enhancer Factor 2 (MEF2) modulators, as well as compositions, pharmaceutical formulations, methods of synthesis and kits. Also provided are methods of treating a condition regulatable by MEF2 and/or MEF2 cofactors using the compounds, compositions, pharmaceutical formulations, and kits provided herein. 1. A compound comprising a structure of Structure I:Y is independently selected from the group consisting of 2-aminophenyl and hydroxyl;{'sub': 2', 'n', '2', 'n', '2', 'n', '2', 'n, 'X is independently selected from the group consisting of —NH—, —NH—(O═C)—(C═OPh)H—, —NHC(═O)—, —C(═O)NH—, —(CH)—NH—, —(CH)—NH—(CH), and —NH—(CH)—, where n is 1, 2, or 3;'}{'sub': 1', '3', '1', '3, 'R-Rare each independently selected from the group consisting of hydrogen, cyclopropyloxy, halogen, ethoxy, methoxy, methyl-mercaptan, ethoxy, ethyl, cyano, isopropyloxy, cyclobutyloxy, cyclopentyloxy, 3-oxetanyloxy, morpholinyl, 4-morpholinyl, dimethylamino, butyl, pyrrolidinyl, ethylmethylamino, piperidinyl, piperazinyl, diethylamino, dimethylaminomethyl, 3-oxetanyl, 2,2-difluoroethoxy, 1,1-difluoroethyl, methylsulfide, trifluoromethylsulfide, 2,2,2-trifluoroethoxy, and trifluoroethoxy, wherein at least one or two of R-Rare not hydrogen; and'}{'sub': 4', '6, 'R-Rare each independently selected from the group consisting of hydrogen and halogen.'}including pharmaceutically acceptable solvates, pharmaceutically acceptable prodrugs, pharmaceutically acceptable salts and pharmaceutically acceptable stereoisomers thereof, wherein: This application claims priority to U.S. Provisional Application No. 62/547,028, filed Aug. 17, 2017, which is incorporated herein by reference.Alterations of epigenetic regulation are a characteristic of many diseases. The myocyte enhancer factor 2 (MEF2) transcription factor plays a central role in the transmission of extracellular signals to the genome and in the activation of the genetic ...

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Номер записи: 87
23-09-2021 дата публикации

CRYSTALLINE DIPEPTIDES USEFUL IN THE SYNTHESIS OF ELAMIPRETIDE

Номер: US20210292274A1
Автор: Duncan Scott M., Redmon Martin P.
Принадлежит:

Disclosed are crystalline forms of L-Lys(Boc)-Phe-NHand Boc-D-Arg-DMT. 4. The crystalline form of claim 3 , wherein said crystalline form has characteristic peaks in its XRPD pattern at values of two theta (° 2θ) of: 4.7 claim 3 , 6.2 claim 3 , 11.3 claim 3 , 12.4 claim 3 , 13.3 claim 3 , 15.0 claim 3 , 15.8 claim 3 , 16.5 claim 3 , 17.0 claim 3 , 17.7 claim 3 , 18.0 claim 3 , 18.2 claim 3 , 18.8 claim 3 , 19.8 claim 3 , 22.0 claim 3 , and 22.8.58-. (canceled) This application is a divisional of U.S. patent application Ser. No. 16/485,369, filed Aug. 12, 2019; which is the U.S. National Stage of PCT/US19/24617, filed Mar. 28, 2019; which claims the benefit of priority to U.S. Provisional Patent Application No. 62/651,430, filed Apr. 2, 2018.Elamipretide (MTP-131) is a mitochondria-targeting peptide compound with therapeutic potential for treating diseases associated with mitochondrial dysfunction. Elamipretide contains four-amino acid residues and has been synthesized according to typical linear and convergent solution phase peptide synthesis methods. The synthetic routes to generate elamipretide that have been used to date require the preparation of various differentially protected peptides, such that certain protecting groups are selectively removed in order to subject the deprotected compound to peptide coupling, while other protecting groups remain to prevent unwanted side reactions. Even with protecting groups such coupling reactions and related steps generate impurities. Thus, there exists a need to develop new methods to purify elamipretide that allow the purification after coupling reactions. Crystallization of the desired reaction products are one method of achieving the necessary purification.Disclosed are crystalline forms of L-Lys(Boc)-Phe-NHand Boc-D-Arg-DMT, wherein DMT is an abbreviation for dimethyltyrosine, which are intermediates in the synthesis of elamipretide.Elamipretide has been shown to have various therapeutic effects in diseases related to ...

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Номер записи: 88
06-09-2018 дата публикации

METHOD OF TREATING OR PREVENTING RAS-MEDIATED DISEASES

Номер: US20180251443A9
Автор: Boyd Michael R., Chen Xi, KEETON Adam B., Piazza Gary A.
Принадлежит:

Disclosed are compounds, for example, a compound of formula I, wherein R, R, R-R, n, X, Y, Y′, and E are as described herein, pharmaceutical compositions containing such compounds, and methods of treating or preventing a disease or condition for example, cancer, mediated by the ras gene. 2. The compound or salt for use according to claim 1 , wherein Ris selected from fluorine and methoxy.3. The compound or salt for use according to claim 1 , wherein Ris selected from hydrogen claim 1 , hydroxyl claim 1 , halogen claim 1 , alkyl claim 1 , amino claim 1 , and dialkylamino.4. The compound or salt for use according to claim 3 , wherein Ris selected from hydroxy and amino.5. The compound or salt for use according to claim 1 , wherein the heterocycle of the heterocyclyl and heterocycloalkyl is selected from pyridinyl claim 1 , piperidinyl claim 1 , piperazinyl claim 1 , and pyrrolidinyl.6. The compound or salt for use according to claim 1 , wherein R′ is phenyl or arylalkyl claim 1 , optionally substituted on the phenyl or the aryl of the arylalkyl by one or more halogen atoms.7. The compound or salt for use according to claim 1 , wherein said selectivity index is at least ten.8. The compound or salt for use according to claim 7 , wherein said selectivity index is at least one hundred.9. The compound or salt for use according to claim 1 , wherein said compound is selected from:(Z)-N-(2-(dimethylamino)ethyl)-2-(1-(4-hydroxy-3,5-dimethoxybenzylidene)-5-methoxy-2-methyl-1H-inden-3-yl)acetamide (003),(Z)-2-(1-(4-hydroxy-3,5-dimethoxybenzylidene)-5-methoxy-2-methyl-1H-inden-3-yl)-N-(pyridin-3-yl)acetamide (004),(Z)-2-(1-(4-hydroxy-3,5-dimethoxybenzylidene)-5-methoxy-2-methyl-1H-inden-3-yl)-N-(pyridin-3-ylmethyl)acetamide (009),(Z)-2-(5-fluoro-1-(4-hydroxy-3,5-dimethoxybenzylidene)-2-methyl-1H-inden-3-yl)-N-(pyridin-2-ylmethyl)acetamide (010),(Z)-2-(5-fluoro-1-(4-hydroxy-3,5-dimethoxybenzylidene)-2-methyl-1H-inden-3-yl)-N-(pyridin-3-ylmethyl)acetamide (011),(Z)-N-benzyl-2-(5- ...

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Номер записи: 89
27-11-2014 дата публикации

STEREOSELECTIVE SYNTHESIS OF METYROSINE

Номер: US20140350284A1
Автор: CHEN Zhengming, COMELY Alex, HALLORAN Kevin John, Krishnan Shyam
Принадлежит:

Provided herein are compositions including diastereomers in substantially diastereomerically pure form and enantiomers in substantially enantiomerically pure form, and processes for preparing them and converting them to metyrosine. 3. The isolated stereoisomer of claim 1 , wherein Ris methyl.4. The isolated stereoisomer of claim 2 , wherein Ris methyl.6. The isolated stereoisomer of claim 4 , wherein Ris methyl.8. The isolated stereoisomer of claim 6 , wherein Ris CONH.9. The isolated stereoisomer of claim 7 , wherein Ris —CN.10. The isolated stereoisomer of claim 1 , wherein Ris —CN.15. The isolated stereoisomer of claim 1 , wherein the compound of formula X is at least about 95% diastereomerically pure.16. The isolated stereoisomer of claim 2 , wherein the compound of formula X-B is at least about 95% diastereomerically pure.17. The isolated stereoisomer of claim 11 , wherein the compound of formula X is at least about 95% diastereomerically pure. This application claims priority from U.S. Provisional Application 61/256,926, filed Oct. 30, 2009, incorporated herein by reference in its entirety.The present technology relates to compositions and processes useful for the stereoselective synthesis of metyrosine and relates generally to the field of organic chemistry.Metyrosine, which has the structure of Formula:is useful in reducing elevated levels of catecholamines associated with pheochromocytoma, and preventing hypertension. Metyrosine, as shown, is a chiral compound. The synthesis of metyrosine in pure or substantially pure enantiomeric form requires a process that involves using substantially diastereomerically and/or enantiomerically pure intermediates. The Applicant has discovered, surprisingly, certain compounds that are substantially diastereomerically or enantiomerically pure and processes to prepare them, and which compounds may be converted to metyrosine.Compositions are provided that include diastereomers in substantially diastereomerically pure form and ...

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Номер записи: 90
27-11-2014 дата публикации

ALISKIREN HEMIFUMARATE, CRYSTAL FORM AND AMORPHOUS SOLID

Номер: US20140350300A1
Автор: Badone Domenico, C.K. Lau, Jiandong Yuan
Принадлежит: DJADA PHARMACEUTICAL SA

Aliskiren hemi fumarate has novel distinctive physico-chemical properties. An amorphous solid is also made of the same Aliskiren hemi fumarate. process for the prepares the forms of Aliskiren hemifumarate. 1. An amorphous form of Aliskiren hemifumarate with a melting point between 87 and 107° C.2. The amorphous form of Aliskiren hemifumarate according to claim 1 , wherein a XRPD diffractogram exhibits the following main peaks a 2theta+/−0.3 degrees: 7 claim 1 ,3 claim 1 , 10.2 claim 1 , 10.4 claim 1 , 19.6.3. The amorphous form according to claim 2 , characterised by the following XRPD diffractogram of :4. A process for preparing an amorphous form of Aliskiren hemifumarate ethyl acetate solvate that comprises:i) dissolving Aliskiren hemifumarate in alcohol and heating to a suitable temperature;ii) coating the solution obtained in i) to room temperature and spiking of same with pure Aliskiren hemifumarate;iii) stirring the mix obtained in ii) at a suitable temperature and for a suitable time;iv) further cooling the mix and continuing the stirring;v) filtering the mix obtained in iv) in order to isolate the precipitate;vi) washing the precipitate with alcohol and drying under vacuum.5. The process according to claim 4 , wherein said phase i) stirring is carried out at a temperature of between 35 and 55° C. and said alcohol is selected from the group consisting of methanol claim 4 , ethanol claim 4 , propanol claim 4 , butanol claim 4 , isopropanol claim 4 , and isobutanol.6. The process according to claim 4 , wherein said phase iii) stirring is continued for 10-20 hours at a temperature of between about 20 and about 25° C. and in said phase iv) is cooled to a temperature below 10° C. and said stirring is continued for 2 hours or more and in said phase vi) the alcohol is selected in the group that comprises methanol claim 4 , ethanol claim 4 , propanol claim 4 , butanol claim 4 , isopropanol claim 4 , and isobutanol claim 4 , and said washing is repeated twice.7. The ...

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Номер записи: 91
13-08-2020 дата публикации

PHENYLPIPERAZINE PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) MODULATORS AND THEIR USE

Номер: US20200253958A1
Автор: Barta Thomas E., Bourne Jonathan William, Bowers Simeon, Monroe Kyle D., Muehlemann Michael M., Pandey Anjali
Принадлежит:

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels. 112.-. (canceled)14. The method of claim 13 , whereby the rate of low density lipoprotein receptor internalization is increased.15. The method of claim 13 , whereby the rate of low density lipoprotein internalization is increased.16. The method of claim 13 , wherein the compound is formulated as a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient.17. The method of claim 16 , wherein said pharmaceutical composition further comprises a second pharmaceutical drug compound.18. The method of claim 17 , wherein said second pharmaceutical drug compound is selected from the group consisting of a statin claim 17 , a cardiovascular drug claim 17 , a metabolic drug claim 17 , and an antihypertensive drug.19. The method of claim 13 , where the compound is selected from:1 -(4-benzylphenyl)piperazine;1-(4-(benzyloxy)phenyl)piperazine;1-(4-phenoxyphenyl)piperazine;1-(4-(4-bromophenoxy)phenyl)piperazine;1-(4-(4-(methylthio)phenoxy)phenyl)piperazine;1-4-(4-(piperazin-1-yl)phenoxy)benzoic acid;4-(4-(piperazin-1-yl)phenoxy)benzoic acid;4-(4-(piperazin-1-yl)phenoxy) ...

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Номер записи: 92
29-09-2016 дата публикации

COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS

Номер: US20160280671A1
Автор: Duggan Karen Annette
Принадлежит:

The present invention relates to novel compounds and their use in the prophylactic and/or therapeutic treatment of hypertension and/or fibrosis. 2. The compound claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , according to wherein Q is halo selected from the group consisting of F claim 1 , Cl claim 1 , Br and I.3. The compound claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , according to claim 1 , wherein Q is substituted amino of the formula —NHW and wherein:{'sub': 2', 'a', 'a, 'W is selected from —CN, —SO(X)Y and —CO(X)Y,'}a is 0 or 1,X is selected from —NH— and —O—, and{'sub': 3', '2', '3', '2', '2', '2, 'Y is selected from —H, —CH, —CHCH, —CHOH and —CHCHOH.'}4. The compound claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , according to claim 1 , wherein Q is substituted amino selected from the group consisting of —NHSOCH claim 1 , —NHCOH claim 1 , —NHCONHCH claim 1 , —NHCONHCHCH—NHSONHCH claim 1 , —NHSONHCHCH claim 1 , —NHCOCH claim 1 , —NHCOOCH claim 1 , —NHCOOCHCHOH claim 1 , —NHCONHand —NHCN.5. The compound claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , according to wherein Q is alkyl selected from the group consisting of methyl claim 1 , ethyl claim 1 , propyl claim 1 , butyl and pentyl.8. A pharmaceutical composition comprising a compound claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , according to and a pharmaceutically-acceptable excipient.9. A method for the therapeutic treatment of hypertension or prehypertension in a subject comprising administering to the subject a compound claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , according to .10. A method for the prophylactic treatment of fibrosis in a subject comprising administering to the subject a compound claim 1 , or a stereoisomer or pharmaceutically acceptable salt thereof claim 1 , according to .11. A ...

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Номер записи: 93
12-10-2017 дата публикации

PLASMINOGEN ACTIVATOR INHIBITOR-1 INHIBITORS AND METHODS OF USE THEREOF

Номер: US20170291893A1
Автор: Abernathy Gregory, Emal Cory, Lawrence Daniel A., Li Shih-Hon, Reinke Ashley, Warnock Mark
Принадлежит:

The invention relates to plasminogen activator- (PAI-) inhibitor compounds and uses thereof in the treatment of any disease or disorder associated with elevated PAI-. The invention includes, but is not limited to, the use of such compounds to prevent or reduce thrombosis and fibrosis, to promote thrombolysis, and to modulate lipid metabolism and treat diseases or disorders associated with elevated PAI-, cholesterol, or lipid levels. 6. The compound of claim 1 , wherein Ris OH.10. The compound of claim 9 , wherein at most three of X claim 9 , X claim 9 , X claim 9 , X claim 9 , and Xare H.17. The compound of claim 16 , wherein Ris selected from the group consisting of butyl claim 16 , pentyl claim 16 , hexyl claim 16 , heptyl claim 16 , octyl claim 16 , nonyl claim 16 , and decyl.18. The compound of claim 16 , wherein Ris selected from the group consisting of butyl claim 16 , pentyl claim 16 , hexyl claim 16 , heptyl claim 16 , octyl claim 16 , nonyl claim 16 , decyl claim 16 , fluorophenyl claim 16 , chlorophenyl claim 16 , bromophenyl claim 16 , iodophenyl claim 16 , trifluoromethylphenyl claim 16 , and dichlorohydroxyphenyl.27. The compound of claim 26 , wherein Rand Rare independently selected from the group consisting of butyl claim 26 , pentyl claim 26 , cyclopropyl claim 26 , phenyl claim 26 , difluorophenyl claim 26 , and hydroxyphenyl.36. The compound of claim 34 , wherein Xand Xare independently selected from the group consisting of —OH and —OR.401. A composition comprising an isolated compound according to any one of Formulas I to XIX claim 34 , C256 claim 34 , C259 claim 34 , C265 claim 34 , C267 claim 34 , C276 claim 34 , C277 claim 34 , C288 claim 34 , C309 claim 34 , C311 claim 34 , C280 claim 34 , C300 claim 34 , C313 claim 34 , C314 claim 34 , C320 claim 34 , C323 claim 34 , C326 claim 34 , C328 claim 34 , C334 claim 34 , C342 claim 34 , C240 claim 34 , C241 claim 34 , C246 claim 34 , C248 claim 34 , C251 claim 34 , C255 claim 34 , C260 claim 34 , ...

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Номер записи: 94
19-10-2017 дата публикации

Process for the Preparation of (S)-4-Methyl-N-((S)-1-(((S)-4-Methyl-1-((R)-2-Methyloxiran-2-YL)-1-OXO Pentan-2-YL) Amino)-1-OXO-3-Phenylpropan-2-YL)-2-((S)-2-(2-Morpholinoacetamido)-4-Phenylbutanamido) Pentanamide

Номер: US20170298093A1
Автор: NANDA KUMAR Mecheril Valsan, Pendyala Surya Bala Subrahmanyam, Pitta Bhaskar Reddy, Pullagurla Manik Reddy, Rangisetty Jagadeesh Babu
Принадлежит: Biophore India Pharmaceuticals Pvt. Ltd

Novel methods for preparation of Carfilzomib and intermediates thereof with high stereo selection are reported. The synthetic procedures result in substantially pure Carfilzomib (I). 8. A substantially pure Carfilzomib (I) obtained by the process of having isomeric purity greater than or equal to 99.5%.9. A substantially pure Carfilzomib (I) obtained by the process of having isomeric purity greater than or equal to 99.5%. Carfilzomib (I) chemically known as (S)-4-methyl-N—((S)-1-(((S)-4-methyl-1-((R)-2-methyl oxiran-2-yl)-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-(2-morpholino acetamido)-4-phenylbutanamido)pentanamide is a tetrapeptideepoxyketone and a selective proteasome inhibitor. Chemically it is also known as (2S)—N—((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran2-yl)-1-oxopentan-2-ylcarbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4-methylpentanamide.U.S. Pat. Nos. 7,232,818, 8,207,297, 8,367,617, 7,417,042 & US publication 20050256324 reported various processes for the syntheses of Carfilzomib, the contents of which are hereby incorporated as reference in their entirety. The general route of synthesis reported in these patents essentially involves the use of a chiral epoxide III. This epoxide is coupled with tripeptide II to obtain Carfilzomib.The yield and purity of Carfilzomib synthesized largely depends on the isomeric purity of the epoxide (III).Therefore the synthesis of a chiral pure epoxide poses a challenge to obtain a substantially pure Carfilzomib.US 20050256324 application explains two different routes of synthesis for the chiral epoxide.In the first process, a keto alkene was converted into an alcohol derivative, which was subsequently epoxidized to obtain a mixture of diastereomers, from which the desired isomer of epoxide (III)(S)-2-amino-4-methyl-1-((R)-2-methyloxiran-2-yl)pentan-1-one, was isolated by column chromatography.In the second process, the keto alkene was directly subjected to epoxidation ...

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Номер записи: 95
10-09-2020 дата публикации

Crystalline dipeptides useful in the synthesis of elamipretide

Номер: US20200283476A1
Автор: Martin P. Redmon, Scott M. Duncan
Принадлежит: Stealth Biotherapeutics Corp

Disclosed are crystalline forms of L-Lys(Boc)-Phe-NH2 and Boc-D-Arg-DMT.

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Номер записи: 96
24-09-2020 дата публикации

Biologically Active Cannabidiol Analogs

Номер: US20200297688A1
Автор: Hannah Marie Harris, Kenneth Joseph SUFKA, Mahmoud A. Elsohly, Mohammad Khalid Ashfaq, Soumyajit Majumdar, Waseem Gul
Принадлежит: UNIVERSITY OF MISSISSIPPI

Biologically active cannabidiol analogs comprising a compound of the formula wherein one of R 1 or R 2 or both is/are the residue of a moiety formed by the reaction of an amino group of the amino acid ester of R 1 or R 2 or both with a dicarboxylic acid or a dicarboxylic acid derivative and the other R 1 or R 2 (in the case of the mono) is the residue of a dicarboxylic acid or dicarboxylic acid derivative or Hydrogen (H), (i.e. underivatized), and salts thereof. These CBD analogs are be useful in pain management in oncology and other clinical settings in which neuropathy is presented. Furthermore, these CBD-analogs are useful in blocking the addictive properties of opiates.

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Номер записи: 97
10-10-2019 дата публикации

Prodrugs of Chlorokynurenines

Номер: US20190308934A1
Автор: Laufer Ralph, Ott Gregory R.
Принадлежит:

The present disclosure relates to prodrugs of 7-chlorokynurenic acid. In certain embodiments, the prodrugs include those having the structure of any one of formula (I)-(VIII), wherein R-R, monomer 1, monomer 2, and linker are defined herein. Also provided are methods of preparing and using these prodrugs. 4. The compound of claim 2 , wherein Ris optionally substituted Calkyl optionally substituted with optionally substituted aryl claim 2 , Calkyl substituted with optionally substituted heterocyclyl claim 2 , or optionally substituted aryl.5. The compound of claim 2 , wherein Ris alkylene glycol optionally substituted by C(O)aryl claim 2 , Calkyl claim 2 , phenyl claim 2 , —P(O)(OH) claim 2 , —P(O)(OH)(OCalkyl) claim 2 , or —S(O)OH.6. The compound of claim 2 , wherein Ris H.7. The compound of claim 2 , wherein Ris Calkyl or Calkoxy.10. The compound of claim 11 , wherein Ris Calkyl claim 11 , Calkoxy claim 11 , or optionally substituted arylCalkyleneoxyl.11. The compound of claim 11 , wherein Ris optionally substituted Ccycloalkyl claim 11 , optionally substituted aryl claim 11 , optionally substituted heteroaryl claim 11 , or optionally substituted heterocyclyl.12. The compound of claim 11 , wherein Ris —NH claim 11 , —NHCalkyl claim 11 , or —N(Calkyl).13. The compound of claim 11 , wherein Ris H or optionally substituted Calkyl.16. The compound of claim 18 , wherein said peptide moiety comprises 2 to about 4 amino acids.18. The compound of claim 1 , wherein one or more H is replaced with H claim 1 , one or more C is replaced with C claim 1 , or one or more N is replaced with N.19. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.20. A method of treating a neurodegenerative disorder claim 1 , enhancing learning claim 1 , memory claim 1 , or cognition claim 1 , treating a condition caused by neurological dysfunction claim 1 , treating depression claim 1 , treating hyperalgesia or reducing a L-DOPA associated dyskinesia ...

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Номер записи: 98
01-10-2020 дата публикации

ALPHA-AMINOAMIDE DERIVATIVE COMPOUND AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

Номер: US20200308104A1
Автор: CHOI Ji Won, CHOO Hyun Ah, HEO Jun Young, JANG Bo Ko, JO Seon Mi, JU Eun Ji, Kang Yong Koo, Kim Dong Jin, KIM Yun Kyung, LEE Changjoon Justin, MIN Sun Joon, NAM Min Ho, PAE Ae Nim, PARK Jong-Hyun, PARK Ki Duk, SONG Hyo Jung, Yeon Seul Ki
Принадлежит:

The present disclosure relates to an α-aminoamide derivative compound and a pharmaceutical composition containing the same. According to various embodiments of the present disclosure, provided is a therapeutic agent which can overcome the disadvantages of existing drugs used as a MAO-B inhibitor and, specifically, reversibly inhibits MAO-B through a non-covalent bond so as to alleviate or eliminate the side effects of the existing drugs which exhibit a therapeutic effect by irreversibly acting via a covalent bond with MAO-B. Particularly, a new compound having superior stability and efficacy compared to the existing reversible MAO-B inhibitors may be provided. 2. The α-aminoamide derivative or the pharmaceutically acceptable salt thereof according to claim 1 ,wherein{'sub': 1', '7, 'R is selected from hydrogen and C-Calkyl; and'}{'sub': 1', '7', '1', '7', '1', '7', '1', '7, 'X is selected from a halogen, C-Calkyl, halogenated C-Calkyl, C-Calkoxy and halogenated C-Calkoxy.'}3. The α-aminoamide derivative or the pharmaceutically acceptable salt thereof according to claim 1 ,whereinR is selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl; andX is selected from halogenated methyl, halogenated ethyl, halogenated methoxy, halogenated ethoxy, methoxy and ethoxy.4. The α-aminoamide derivative or the pharmaceutically acceptable salt thereof according to claim 1 ,whereinR is selected from hydrogen, methyl, isopropyl and isobutyl; andX is selected from fluoro, chloro, trifluoromethyl, trifluoromethoxy and methoxy.5. The α-aminoamide derivative or the pharmaceutically acceptable salt thereof according to claim 1 ,whereinR is selected from hydrogen, methyl, isopropyl and isobutyl; andX is selected from p-trifluoromethyl, p-trifluoromethoxy, m-trifluoromethyl, m-trifluoromethoxy, p-chloro, m-chloro, p-methoxy, m-methoxy, p-fluoro and m-fluoro.6. The α-aminoamide derivative or the pharmaceutically acceptable salt ...

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Номер записи: 99
01-10-2020 дата публикации

CYCLOPROPYL-AMIDE COMPOUNDS AS DUAL LSD1/HDAC INHIBITORS

Номер: US20200308110A1
Автор: DEWANG Purushottam, GAJENDRAN Chandru, HALLUR Mahanandeesha S., IYER Pravin, KUMAR C.H. Durga Prasanna, MULAKALA Chandrika, MURUGAN Kannan, NAIR Sreekala, RAJAGOPAL Sridharan, Rajagopal Sriram, SIVANANDHAN Dhanalakshmi, TANTRY Subramanyam Janardhan, ZAINUDDIN Mohd
Принадлежит:

The present disclosure describes novel compounds of the general Formula (I), their analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites, and prodrugs thereof. These compounds can inhibit both LSD and HDAC and are useful as therpeautic or ameliorating agent for diseases that are involved in cellular growth such as malignant tumors, schizophrenia, Alzheimer's disease, parkinson's disease and the like. 2. The compound of Formula (I) as claimed in claim 1 , or analogs claim 1 , tautomeric forms claim 1 , stereoisomers claim 1 , polymorphs claim 1 , solvates claim 1 , intermediates claim 1 , pharmaceutically claim 1 , acceptable salts claim 1 , metabolites claim 1 , and prodrugs thereof claim 1 , wherein:{'sub': 5-6', '1-6', '2-10, 'Ar is selected from the group consisting of substituted or unsubstituted Caryl, Cheteroaryl, and Cheterocyclyl with heteroatoms selected from N, O, S;'}{'sub': 4', '5, 'claim-text': {'sub': 4', '5', '1-8, 'wherein Rand Rare independently selected from the group consisting of hydrogen, and substituted or unsubstituted Calkyl;'}, 'W represents a bond or CRR,'}{'sub': 1-8', '2-8', '2-8', '5-6', '1-6', '2-10', '3-8', '2-10, 'claim-text': {'sub': 1-8', '5-6', '1-6', '2-10', '3-8', '1-6', '3-8, 'wherein Calkyl, Caryl, Cheteroaryl, Cheterocyclyl, Ccycloalkyl, is optionally substituted with one or more of the groups selected from hydrogen, Calkyl, oxo (═O), Ccycloalkyl, halogen, OH, and cyano;'}, 'Y is a bond or is selected from the group consisting of substituted or unsubstituted Calkyl, Calkenyl, Calkynyl, Caryl, Cheteroaryl, Cheterocyclcyl, Ccycloalkyl, —CO—, and —CO—Cheterocyclyl,'}{'sub': 1-8', '2-8', '2-8', '7-12', '7-12', '7-15', '2-12', '7-12', '7-12', '6', '1-8', '1-8', '6', '5-6', '5-6', '1-6', '2-10', '2-10', '6', '1-8', '6', '1-8', '6', '5-6', '6', '5-6', '6', '1-6', '1-8', '5-6', '5-6', '1-6', '6', '5-6', '6', '7-12', '6', '7-12', '2', '5-6', ...

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Номер записи: 100