JP5411141B2 - 細胞内カルシウムを調節する化合物 - Google Patents
細胞内カルシウムを調節する化合物 Download PDFInfo
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- JP5411141B2 JP5411141B2 JP2010524085A JP2010524085A JP5411141B2 JP 5411141 B2 JP5411141 B2 JP 5411141B2 JP 2010524085 A JP2010524085 A JP 2010524085A JP 2010524085 A JP2010524085 A JP 2010524085A JP 5411141 B2 JP5411141 B2 JP 5411141B2
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- Prior art keywords
- thiophene
- carboxylic acid
- calcium
- chlorophenyl
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 150000001875 compounds Chemical class 0.000 title claims description 304
- 239000011575 calcium Substances 0.000 title description 401
- 229910052791 calcium Inorganic materials 0.000 title description 305
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title description 303
- 230000003834 intracellular effect Effects 0.000 title description 93
- -1 4-chlorobenzamido Chemical group 0.000 claims description 144
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 135
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 113
- 150000003839 salts Chemical class 0.000 claims description 99
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 80
- 201000010099 disease Diseases 0.000 claims description 76
- 125000001424 substituent group Chemical group 0.000 claims description 70
- 229910052739 hydrogen Inorganic materials 0.000 claims description 61
- 229910052801 chlorine Inorganic materials 0.000 claims description 60
- 229910052731 fluorine Inorganic materials 0.000 claims description 60
- 125000003118 aryl group Chemical group 0.000 claims description 59
- 229910052794 bromium Inorganic materials 0.000 claims description 59
- 229910052740 iodine Inorganic materials 0.000 claims description 59
- 208000035475 disorder Diseases 0.000 claims description 57
- 239000001257 hydrogen Substances 0.000 claims description 46
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 43
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 31
- 150000002431 hydrogen Chemical class 0.000 claims description 31
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 28
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 27
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 24
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 24
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
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- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 13
- 230000004054 inflammatory process Effects 0.000 claims description 13
- 206010052779 Transplant rejections Diseases 0.000 claims description 12
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 10
- 210000000056 organ Anatomy 0.000 claims description 10
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- DBPKFTINUNROTG-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-[3-(3-chlorophenyl)propanoylamino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Cl)=CC=2)C(C(=O)O)=C1NC(=O)CCC1=CC=CC(Cl)=C1 DBPKFTINUNROTG-UHFFFAOYSA-N 0.000 claims description 7
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 7
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- 238000006467 substitution reaction Methods 0.000 claims description 7
- PXGYUBINGLWGPU-UHFFFAOYSA-N 4-(4-bromophenyl)-2-[(3-fluorobenzoyl)amino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Br)=CC=2)C(C(=O)O)=C1NC(=O)C1=CC=CC(F)=C1 PXGYUBINGLWGPU-UHFFFAOYSA-N 0.000 claims description 6
- BTRWFHPWJJOKAL-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-[3-(3-fluorophenyl)propanoylamino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Cl)=CC=2)C(C(=O)O)=C1NC(=O)CCC1=CC=CC(F)=C1 BTRWFHPWJJOKAL-UHFFFAOYSA-N 0.000 claims description 6
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- DZOVNYIHSJWERL-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-(3-phenylpropanoylamino)thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Cl)=CC=2)C(C(=O)O)=C1NC(=O)CCC1=CC=CC=C1 DZOVNYIHSJWERL-UHFFFAOYSA-N 0.000 claims description 5
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- SEMSENMTSCLCPW-UHFFFAOYSA-N 2-[(2-chloro-4-fluorobenzoyl)amino]-4-(4-chlorophenyl)thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Cl)=CC=2)C(C(=O)O)=C1NC(=O)C1=CC=C(F)C=C1Cl SEMSENMTSCLCPW-UHFFFAOYSA-N 0.000 claims description 4
- OKFFDBYTPKPSOR-UHFFFAOYSA-N 2-[(4-bromobenzoyl)amino]-4-(4-chlorophenyl)thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Cl)=CC=2)C(C(=O)O)=C1NC(=O)C1=CC=C(Br)C=C1 OKFFDBYTPKPSOR-UHFFFAOYSA-N 0.000 claims description 4
- DCHPIQBGCGQKCM-UHFFFAOYSA-N 4-(4-bromophenyl)-2-[(2-chloro-4-fluorobenzoyl)amino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Br)=CC=2)C(C(=O)O)=C1NC(=O)C1=CC=C(F)C=C1Cl DCHPIQBGCGQKCM-UHFFFAOYSA-N 0.000 claims description 4
- QNXRDAVIADLKCK-UHFFFAOYSA-N 4-(4-bromophenyl)-2-[(2-fluorobenzoyl)amino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Br)=CC=2)C(C(=O)O)=C1NC(=O)C1=CC=CC=C1F QNXRDAVIADLKCK-UHFFFAOYSA-N 0.000 claims description 4
- NRVKDCQHKRCBLD-UHFFFAOYSA-N 4-(4-bromophenyl)-2-[(3,4-difluorobenzoyl)amino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Br)=CC=2)C(C(=O)O)=C1NC(=O)C1=CC=C(F)C(F)=C1 NRVKDCQHKRCBLD-UHFFFAOYSA-N 0.000 claims description 4
- DRQNMCYZPREQRJ-UHFFFAOYSA-N 4-(4-bromophenyl)-2-[(3-fluoro-4-methoxybenzoyl)amino]thiophene-3-carboxylic acid Chemical compound C1=C(F)C(OC)=CC=C1C(=O)NC1=C(C(O)=O)C(C=2C=CC(Br)=CC=2)=CS1 DRQNMCYZPREQRJ-UHFFFAOYSA-N 0.000 claims description 4
- VHZIYRHPROFEMO-UHFFFAOYSA-N 4-(4-bromophenyl)-2-[3-(2,4-difluorophenyl)propanoylamino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Br)=CC=2)C(C(=O)O)=C1NC(=O)CCC1=CC=C(F)C=C1F VHZIYRHPROFEMO-UHFFFAOYSA-N 0.000 claims description 4
- YBRIENQMGZJMLX-UHFFFAOYSA-N 4-(4-bromophenyl)-2-[3-(3,4-difluorophenyl)propanoylamino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Br)=CC=2)C(C(=O)O)=C1NC(=O)CCC1=CC=C(F)C(F)=C1 YBRIENQMGZJMLX-UHFFFAOYSA-N 0.000 claims description 4
- XXRBXQCBRPYVKA-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-[(4-methylbenzoyl)amino]thiophene-3-carboxylic acid Chemical compound C1=CC(C)=CC=C1C(=O)NC1=C(C(O)=O)C(C=2C=CC(Cl)=CC=2)=CS1 XXRBXQCBRPYVKA-UHFFFAOYSA-N 0.000 claims description 4
- ASQBCIOXNPNBKP-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-[3-(2,4-difluorophenyl)propanoylamino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Cl)=CC=2)C(C(=O)O)=C1NC(=O)CCC1=CC=C(F)C=C1F ASQBCIOXNPNBKP-UHFFFAOYSA-N 0.000 claims description 4
- YWMBSLLFFXFKBF-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-[3-(4-chlorophenyl)propanoylamino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Cl)=CC=2)C(C(=O)O)=C1NC(=O)CCC1=CC=C(Cl)C=C1 YWMBSLLFFXFKBF-UHFFFAOYSA-N 0.000 claims description 4
- FPUHHWYMUBTYKQ-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-[3-(4-fluorophenyl)propanoylamino]thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Cl)=CC=2)C(C(=O)O)=C1NC(=O)CCC1=CC=C(F)C=C1 FPUHHWYMUBTYKQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 4
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 4
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- 201000003883 Cystic fibrosis Diseases 0.000 claims description 4
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- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims description 4
- 208000005615 Interstitial Cystitis Diseases 0.000 claims description 4
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- RQGJBOGLIDKSLE-UHFFFAOYSA-N 2-[(3-fluorobenzoyl)amino]-4-(4-methylphenyl)thiophene-3-carboxylic acid Chemical compound C1=CC(C)=CC=C1C1=CSC(NC(=O)C=2C=C(F)C=CC=2)=C1C(O)=O RQGJBOGLIDKSLE-UHFFFAOYSA-N 0.000 claims description 3
- VNJWGWLHJCVWII-UHFFFAOYSA-N 2-[(4-bromobenzoyl)amino]-4-(3,5-dichlorophenyl)thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=C(Cl)C=C(Cl)C=2)C(C(=O)O)=C1NC(=O)C1=CC=C(Br)C=C1 VNJWGWLHJCVWII-UHFFFAOYSA-N 0.000 claims description 3
- XKADKRFWPHOYIH-UHFFFAOYSA-N 2-[(4-bromobenzoyl)amino]-4-(3-chlorophenyl)thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=C(Cl)C=CC=2)C(C(=O)O)=C1NC(=O)C1=CC=C(Br)C=C1 XKADKRFWPHOYIH-UHFFFAOYSA-N 0.000 claims description 3
- XJTBNLJGGPCAAN-UHFFFAOYSA-N 2-[(4-bromobenzoyl)amino]-4-(4-bromophenyl)thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Br)=CC=2)C(C(=O)O)=C1NC(=O)C1=CC=C(Br)C=C1 XJTBNLJGGPCAAN-UHFFFAOYSA-N 0.000 claims description 3
- UDIWZNZAHJYFMW-UHFFFAOYSA-N 2-[(4-chlorobenzoyl)amino]-4-(3,4-dichlorophenyl)thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=C(Cl)C(Cl)=CC=2)C(C(=O)O)=C1NC(=O)C1=CC=C(Cl)C=C1 UDIWZNZAHJYFMW-UHFFFAOYSA-N 0.000 claims description 3
- NUTHQSADGDMPOK-UHFFFAOYSA-N 2-[(4-chlorobenzoyl)amino]-4-(4-chlorophenyl)thiophene-3-carboxylic acid Chemical compound S1C=C(C=2C=CC(Cl)=CC=2)C(C(=O)O)=C1NC(=O)C1=CC=C(Cl)C=C1 NUTHQSADGDMPOK-UHFFFAOYSA-N 0.000 claims description 3
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- IWIGQJKWMNVSOD-UHFFFAOYSA-N 2-[(4-chlorobenzoyl)amino]-4-(4-methylphenyl)thiophene-3-carboxylic acid Chemical compound C1=CC(C)=CC=C1C1=CSC(NC(=O)C=2C=CC(Cl)=CC=2)=C1C(O)=O IWIGQJKWMNVSOD-UHFFFAOYSA-N 0.000 claims description 3
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| JP6399874B2 (ja) * | 2013-09-20 | 2018-10-03 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 化合物の抗炎症効果または免疫抑制効果を予測する方法 |
| PT2982982T (pt) * | 2014-08-06 | 2018-01-03 | Univ De Bretagne Occidentale U B O | Metedo para rastreio de compostos utilizando uma membrana stim1 |
| ES3033759T3 (en) | 2015-02-27 | 2025-08-07 | Calcimedica Inc | Pancreatitis treatment |
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| AU2018215089C1 (en) | 2017-02-03 | 2022-09-22 | Certa Therapeutics Pty. Ltd. | Anti-fibrotic compounds |
| CN108938625B (zh) * | 2017-05-27 | 2021-06-29 | 北京大学 | 2-芳甲酰胺基噻吩-3-羧酸类衍生物作为ano1蛋白抑制剂的用途及制备方法 |
| CN107496420B (zh) * | 2017-08-25 | 2020-07-07 | 中国科学院微生物研究所 | 环匹阿尼酸类生物碱化合物的用途 |
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| CN116444481B (zh) * | 2022-01-05 | 2025-07-25 | 北京大学 | 作为ano1蛋白抑制剂的4-芳基噻吩甲酸类化合物 |
| CN114948923A (zh) * | 2022-06-02 | 2022-08-30 | 南京中医药大学 | 奥替溴铵及其盐在制备治疗周围神经病变以及肺纤维化药物中的应用 |
Family Cites Families (140)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3472802A (en) | 1966-11-23 | 1969-10-14 | Inter Chem Corp | Novel nitrocellulose flexographic printing inks |
| US3598122A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3993073A (en) | 1969-04-01 | 1976-11-23 | Alza Corporation | Novel drug delivery device |
| US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| ES371373A1 (es) * | 1969-09-10 | 1972-04-01 | Patronato De Investigacion Cie | Procedimiento para la obtencion de derivados de 4-oxo-3- amino-3,4 - dihidrotieno (3,2-d) pirimidina sustituidos. |
| US3710795A (en) | 1970-09-29 | 1973-01-16 | Alza Corp | Drug-delivery device with stretched, rate-controlling membrane |
| US4069307A (en) | 1970-10-01 | 1978-01-17 | Alza Corporation | Drug-delivery device comprising certain polymeric materials for controlled release of drug |
| US3731683A (en) | 1971-06-04 | 1973-05-08 | Alza Corp | Bandage for the controlled metering of topical drugs to the skin |
| US3742951A (en) | 1971-08-09 | 1973-07-03 | Alza Corp | Bandage for controlled release of vasodilators |
| US3996934A (en) | 1971-08-09 | 1976-12-14 | Alza Corporation | Medical bandage |
| BE795384A (fr) | 1972-02-14 | 1973-08-13 | Ici Ltd | Pansements |
| GB1419074A (en) * | 1972-06-09 | 1975-12-24 | Ici Ltd | Process for manufacturing substituted thiophene compounds |
| US3921636A (en) | 1973-01-15 | 1975-11-25 | Alza Corp | Novel drug delivery device |
| US3993072A (en) | 1974-08-28 | 1976-11-23 | Alza Corporation | Microporous drug delivery device |
| US4151273A (en) | 1974-10-31 | 1979-04-24 | The Regents Of The University Of California | Increasing the absorption rate of insoluble drugs |
| US3972995A (en) | 1975-04-14 | 1976-08-03 | American Home Products Corporation | Dosage form |
| GB1548398A (en) * | 1975-06-05 | 1979-07-11 | Lilly Industries Ltd | Acylamino pyrroles furans and thiophenes |
| US4077407A (en) | 1975-11-24 | 1978-03-07 | Alza Corporation | Osmotic devices having composite walls |
| US4031894A (en) | 1975-12-08 | 1977-06-28 | Alza Corporation | Bandage for transdermally administering scopolamine to prevent nausea |
| US4060084A (en) | 1976-09-07 | 1977-11-29 | Alza Corporation | Method and therapeutic system for providing chemotherapy transdermally |
| US4201211A (en) | 1977-07-12 | 1980-05-06 | Alza Corporation | Therapeutic system for administering clonidine transdermally |
| JPS5562012A (en) | 1978-11-06 | 1980-05-10 | Teijin Ltd | Slow-releasing preparation |
| US4230105A (en) | 1978-11-13 | 1980-10-28 | Merck & Co., Inc. | Transdermal delivery of drugs |
| US4229447A (en) | 1979-06-04 | 1980-10-21 | American Home Products Corporation | Intraoral methods of using benzodiazepines |
| CA1146866A (en) | 1979-07-05 | 1983-05-24 | Yamanouchi Pharmaceutical Co. Ltd. | Process for the production of sustained release pharmaceutical composition of solid medical material |
| US4291015A (en) | 1979-08-14 | 1981-09-22 | Key Pharmaceuticals, Inc. | Polymeric diffusion matrix containing a vasodilator |
| US4327725A (en) | 1980-11-25 | 1982-05-04 | Alza Corporation | Osmotic device with hydrogel driving member |
| US4476116A (en) | 1982-12-10 | 1984-10-09 | Syntex (U.S.A.) Inc. | Polypeptides/chelating agent nasal compositions having enhanced peptide absorption |
| US5116817A (en) | 1982-12-10 | 1992-05-26 | Syntex (U.S.A.) Inc. | LHRH preparations for intranasal administration |
| US4596795A (en) | 1984-04-25 | 1986-06-24 | The United States Of America As Represented By The Secretary, Dept. Of Health & Human Services | Administration of sex hormones in the form of hydrophilic cyclodextrin derivatives |
| US4624848A (en) | 1984-05-10 | 1986-11-25 | Ciba-Geigy Corporation | Active agent containing hydrogel devices wherein the active agent concentration profile contains a sigmoidal concentration gradient for improved constant release, their manufacture and use |
| GB8518301D0 (en) | 1985-07-19 | 1985-08-29 | Fujisawa Pharmaceutical Co | Hydrodynamically explosive systems |
| EP0230654B1 (en) | 1985-12-28 | 1992-03-18 | Sumitomo Pharmaceuticals Company, Limited | Sustained pulsewise release pharmaceutical preparation |
| US4755386A (en) | 1986-01-22 | 1988-07-05 | Schering Corporation | Buccal formulation |
| US5312325A (en) | 1987-05-28 | 1994-05-17 | Drug Delivery Systems Inc | Pulsating transdermal drug delivery system |
| US4968509A (en) | 1987-07-27 | 1990-11-06 | Mcneilab, Inc. | Oral sustained release acetaminophen formulation and process |
| US5052558A (en) | 1987-12-23 | 1991-10-01 | Entravision, Inc. | Packaged pharmaceutical product |
| US5033252A (en) | 1987-12-23 | 1991-07-23 | Entravision, Inc. | Method of packaging and sterilizing a pharmaceutical product |
| IL92966A (en) | 1989-01-12 | 1995-07-31 | Pfizer | Dispensing devices powered by hydrogel |
| PH27357A (en) | 1989-09-22 | 1993-06-21 | Fujisawa Pharmaceutical Co | Pyrazole derivatives and pharmaceutical compositions comprising the same |
| US5739136A (en) | 1989-10-17 | 1998-04-14 | Ellinwood, Jr.; Everett H. | Intraoral dosing method of administering medicaments |
| US5017381A (en) | 1990-05-02 | 1991-05-21 | Alza Corporation | Multi-unit pulsatile delivery system |
| US5633009A (en) | 1990-11-28 | 1997-05-27 | Sano Corporation | Transdermal administration of azapirones |
| DE69222847T3 (de) | 1991-04-16 | 2005-09-15 | Nippon Shinyaku Co., Ltd. | Verfahren zur herstellung einer festen dispersion |
| HU227530B1 (en) | 1991-11-22 | 2011-07-28 | Warner Chilcott Company | Delayed-release compositions containing risedronate and process for their production |
| US5229135A (en) | 1991-11-22 | 1993-07-20 | Prographarm Laboratories | Sustained release diltiazem formulation |
| US5340591A (en) | 1992-01-24 | 1994-08-23 | Fujisawa Pharmaceutical Co., Ltd. | Method of producing a solid dispersion of the sparingly water-soluble drug, nilvadipine |
| US5461140A (en) | 1992-04-30 | 1995-10-24 | Pharmaceutical Delivery Systems | Bioerodible polymers for solid controlled release pharmaceutical compositions |
| US5260068A (en) | 1992-05-04 | 1993-11-09 | Anda Sr Pharmaceuticals Inc. | Multiparticulate pulsatile drug delivery system |
| US5281420A (en) | 1992-05-19 | 1994-01-25 | The Procter & Gamble Company | Solid dispersion compositions of tebufelone |
| US5323907A (en) | 1992-06-23 | 1994-06-28 | Multi-Comp, Inc. | Child resistant package assembly for dispensing pharmaceutical medications |
| AU4198793A (en) | 1992-07-24 | 1994-01-27 | Takeda Chemical Industries Ltd. | Microparticle preparation and production thereof |
| US5700485A (en) | 1992-09-10 | 1997-12-23 | Children's Medical Center Corporation | Prolonged nerve blockade by the combination of local anesthetic and glucocorticoid |
| WO1994008568A1 (fr) | 1992-10-16 | 1994-04-28 | Nippon Shinyaku Co., Ltd. | Procede pour fabriquer des matrices de cire |
| BR9307503A (pt) * | 1992-11-23 | 1999-06-29 | Pfizer | Síntese regiosseletiva da ácido 4-cloro-2 tiofenocarboxícilo |
| US5260069A (en) | 1992-11-27 | 1993-11-09 | Anda Sr Pharmaceuticals Inc. | Pulsatile particles drug delivery system |
| US5604260A (en) | 1992-12-11 | 1997-02-18 | Merck Frosst Canada Inc. | 5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2 |
| EP0759432A1 (en) | 1993-01-15 | 1997-02-26 | G.D. Searle & Co. | Use of medicaments containing 3,4-diaryl furans and analogs thereof for treating a skin-related condition |
| US5686105A (en) | 1993-10-19 | 1997-11-11 | The Procter & Gamble Company | Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery |
| US5409944A (en) | 1993-03-12 | 1995-04-25 | Merck Frosst Canada, Inc. | Alkanesulfonamido-1-indanone derivatives as inhibitors of cyclooxygenase |
| US5380738A (en) | 1993-05-21 | 1995-01-10 | Monsanto Company | 2-substituted oxazoles further substituted by 4-fluorophenyl and 4-methylsulfonylphenyl as antiinflammatory agents |
| US5436265A (en) | 1993-11-12 | 1995-07-25 | Merck Frosst Canada, Inc. | 1-aroyl-3-indolyl alkanoic acids and derivatives thereof useful as anti-inflammatory agents |
| US5474995A (en) | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
| GB9602877D0 (en) | 1996-02-13 | 1996-04-10 | Merck Frosst Canada Inc | 3,4-Diaryl-2-hydroxy-2,5- dihydrofurans as prodrugs to cox-2 inhibitors |
| US5344991A (en) | 1993-10-29 | 1994-09-06 | G.D. Searle & Co. | 1,2 diarylcyclopentenyl compounds for the treatment of inflammation |
| US5466823A (en) | 1993-11-30 | 1995-11-14 | G.D. Searle & Co. | Substituted pyrazolyl benzenesulfonamides |
| US5393790A (en) | 1994-02-10 | 1995-02-28 | G.D. Searle & Co. | Substituted spiro compounds for the treatment of inflammation |
| US5665378A (en) | 1994-09-30 | 1997-09-09 | Davis; Roosevelt | Transdermal therapeutic formulation |
| US5633272A (en) | 1995-02-13 | 1997-05-27 | Talley; John J. | Substituted isoxazoles for the treatment of inflammation |
| US5567441A (en) | 1995-03-24 | 1996-10-22 | Andrx Pharmaceuticals Inc. | Diltiazem controlled release formulation |
| JPH11505258A (ja) | 1995-05-17 | 1999-05-18 | セダーシナイ メディカル センター | 小腸における消化および吸収を改善させる脂肪酸を含む組成物 |
| SE9502244D0 (sv) | 1995-06-20 | 1995-06-20 | Bioglan Ab | A composition and a process for the preparation thereof |
| US6020343A (en) | 1995-10-13 | 2000-02-01 | Merck Frosst Canada, Inc. | (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors |
| GB9523946D0 (en) | 1995-11-23 | 1996-01-24 | Bayer Ag | Leukotriene antagonistic benzoic acid derivatives |
| US5837284A (en) | 1995-12-04 | 1998-11-17 | Mehta; Atul M. | Delivery of multiple doses of medications |
| US6323227B1 (en) * | 1996-01-02 | 2001-11-27 | Aventis Pharmaceuticals Products Inc. | Substituted N-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
| US5858401A (en) | 1996-01-22 | 1999-01-12 | Sidmak Laboratories, Inc. | Pharmaceutical composition for cyclosporines |
| US6923983B2 (en) | 1996-02-19 | 2005-08-02 | Acrux Dds Pty Ltd | Transdermal delivery of hormones |
| US6929801B2 (en) | 1996-02-19 | 2005-08-16 | Acrux Dds Pty Ltd | Transdermal delivery of antiparkinson agents |
| RO121338B1 (ro) | 1996-04-12 | 2007-03-30 | G.D. Searle & Co. | Derivaţi de benzensulfonamidă, procedeu de preparare a acestora, compoziţie farmaceutică şi utilizarea ca inhibitori de cox-2 |
| US5861419A (en) | 1996-07-18 | 1999-01-19 | Merck Frosst Canad, Inc. | Substituted pyridines as selective cyclooxygenase-2 inhibitors |
| US6458373B1 (en) | 1997-01-07 | 2002-10-01 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
| US5840329A (en) | 1997-05-15 | 1998-11-24 | Bioadvances Llc | Pulsatile drug delivery system |
| US6037340A (en) * | 1997-05-28 | 2000-03-14 | Cadus Pharmaceutical Corporation | Synthesis and use of thiophene- and pyrrole-based heteroaromatic compounds |
| US6391452B1 (en) | 1997-07-18 | 2002-05-21 | Bayer Corporation | Compositions for nasal drug delivery, methods of making same, and methods of removing residual solvent from pharmaceutical preparations |
| US5869090A (en) | 1998-01-20 | 1999-02-09 | Rosenbaum; Jerry | Transdermal delivery of dehydroepiandrosterone |
| US6946144B1 (en) | 1998-07-08 | 2005-09-20 | Oryxe | Transdermal delivery system |
| DE60039379D1 (de) | 1999-02-10 | 2008-08-21 | Pfizer Prod Inc | Pharmazeutische feste Dispersionen |
| US6395300B1 (en) | 1999-05-27 | 2002-05-28 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
| US6803375B1 (en) * | 2000-01-06 | 2004-10-12 | The Regents Of The University Of California | Non-peptide inhibition of T-lymphocyte activation and therapies related thereto |
| US6313138B1 (en) | 2000-02-25 | 2001-11-06 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| EP1324993A2 (en) * | 2000-04-18 | 2003-07-09 | Cytovia, Inc. | Substituted 1,4-thiazepine and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| WO2002030976A1 (en) | 2000-10-11 | 2002-04-18 | The University Of Melbourne | Cell control nucleic acids and proteins |
| DE10061876A1 (de) | 2000-12-12 | 2002-06-20 | Aventis Pharma Gmbh | Arylierte Furan- und Thiophencarbonsäureamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| US6465014B1 (en) | 2001-03-21 | 2002-10-15 | Isp Investments Inc. | pH-dependent sustained release, drug-delivery composition |
| CN1549714A (zh) | 2001-08-06 | 2004-11-24 | 作为激酶抑制剂的氨基异噁唑衍生物 | |
| US6960563B2 (en) | 2001-08-31 | 2005-11-01 | Morton Grove Pharmaceuticals, Inc. | Spontaneous emulsions containing cyclosporine |
| US6919359B2 (en) * | 2001-11-08 | 2005-07-19 | Pfizer Inc | Azabicyclic-substituted-heteroaryl compounds for the treatment of disease |
| AR040123A1 (es) | 2002-05-31 | 2005-03-16 | Upjohn Co | Compuestos tiofeno, antihelminticos e insecticidas |
| MXPA05000020A (es) * | 2002-07-01 | 2005-12-05 | Pharmacia & Upjohn Co Llc | Inhibidores de polimerasa ns5b de la infeccion del virus de la hepatitis c (hcv). |
| EP1558277B1 (en) * | 2002-10-16 | 2011-05-18 | Promics Pty Limited | Treatment of inflammatory bowel disease |
| AR043057A1 (es) | 2002-10-30 | 2005-07-13 | Vertex Pharma | Compuestos derivados de piridintiazoles como inhibidores de la quinasa rock y otras proteinas quinasa |
| WO2004078995A2 (en) | 2003-03-04 | 2004-09-16 | Neurogenetics, Inc. | Methods of modulating and of identifying agents that modulate intracellular calcium |
| US7060697B2 (en) | 2003-05-19 | 2006-06-13 | Irm Llc | Immunosuppressant compounds and compositions |
| AU2003902851A0 (en) | 2003-06-06 | 2003-06-26 | Australian Ballet School | Ballet shoe insert |
| JP4979378B2 (ja) | 2003-07-23 | 2012-07-18 | シンタ ファーマシューティカルズ コーポレーション | 炎症及び免疫関連の使用のための化合物 |
| US20050085531A1 (en) | 2003-10-03 | 2005-04-21 | Hodge Carl N. | Thiophene-based compounds exhibiting ATP-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| WO2005048942A2 (en) | 2003-11-13 | 2005-06-02 | Pharmacia Corporation | Combination therapy comprising a cox-2 inhibitor and an antineoplastic agent |
| WO2006093518A2 (en) | 2004-06-25 | 2006-09-08 | Apath, Llc | Thienyl compounds for treating virus-related conditions |
| US20060223812A1 (en) * | 2004-07-17 | 2006-10-05 | Max-Planck-Gesellschaft Zur Forderungder Wissenschaften, E.V. | Treating neurodegenerative conditions |
| WO2006007864A1 (en) | 2004-07-17 | 2006-01-26 | Max Planck Geselllschaft Zur Förderung Der Wissenschaft | Treating neurodegenerative conditions |
| AU2005266890C1 (en) | 2004-07-30 | 2014-09-25 | Exelixis, Inc. | Pyrrole derivatives as pharmaceutical agents |
| WO2006034402A2 (en) * | 2004-09-21 | 2006-03-30 | Synta Pharmaceutical Corp. | Compounds for inflammation and immune-related uses |
| TWI441819B (zh) | 2005-01-07 | 2014-06-21 | Synta Pharmaceuticals Corp | 用於炎症及免疫相關用途之化合物 |
| AU2006208045B2 (en) | 2005-01-25 | 2012-08-30 | Synta Pharmaceuticals Corp. | Compounds for inflammation and immune-related uses |
| JP5221147B2 (ja) | 2005-01-25 | 2013-06-26 | シンタ ファーマシューティカルズ コーポレーション | 炎症及び免疫に関連する用途に用いる化合物 |
| CA2597430C (en) | 2005-02-17 | 2014-08-05 | Synta Pharmaceuticals Corp. | Isoxazole combretastin derivatives for the treatment of disorders |
| US7563813B2 (en) * | 2005-05-13 | 2009-07-21 | Wyeth | Iminothiazolidinone derivatives as SFRP-1 antagonists |
| GB0516379D0 (en) | 2005-08-09 | 2005-09-14 | Glaxo Group Ltd | Compounds |
| EP1754483A1 (en) | 2005-08-18 | 2007-02-21 | Merck Sante | Use of thienopyridone derivatives as AMPK activators and pharmaceutical compositions containing them |
| EP1984400B1 (en) | 2006-01-05 | 2012-11-28 | Immune Disease Institute, Inc. | Regulators of nfat |
| JPWO2007083689A1 (ja) | 2006-01-19 | 2009-06-11 | 株式会社レナサイエンス | プラスミノーゲンアクチベーターインヒビター−1阻害剤 |
| EP1983831A4 (en) | 2006-01-25 | 2010-11-24 | Synta Pharmaceuticals Corp | PHENYL AND PYRIDIL COMPOUNDS FOR INFLAMMATION AND IMMUNOUS USE |
| CA2639927A1 (en) * | 2006-01-25 | 2007-08-02 | Synta Pharmaceuticals Corp. | Substituted biaryl compounds for inflammation and immune-related uses |
| EP1983971A4 (en) * | 2006-01-25 | 2010-11-24 | Synta Pharmaceuticals Corp | SUBSTITUTED AROMATIC COMPOUNDS FOR USE AGAINST INFLAMMATION AND IMMUNE DISORDERS |
| WO2007087427A2 (en) * | 2006-01-25 | 2007-08-02 | Synta Pharmaceuticals Corp. | Thiazole and thiadiazole compounds for inflammation and immune-related uses |
| WO2007087443A2 (en) * | 2006-01-25 | 2007-08-02 | Synta Pharmaceuticals Corp. | Vinyl-phenyl derivatives for inflammation and immune-related uses |
| AU2007211276B2 (en) * | 2006-01-31 | 2013-06-06 | Synta Pharmaceuticals Corp. | Pyridylphenyl compounds for inflammation and immune-related uses |
| US8119643B2 (en) * | 2006-03-20 | 2012-02-21 | Synta Pharmaceuticals Corp. | Benzoimidazolyl-pyrazine compounds for inflammation and immune-related uses |
| EP2004626A4 (en) * | 2006-03-23 | 2010-10-27 | Synta Pharmaceuticals Corp | BENZIMIDAZOLYL-PYRIDINE COMPOUNDS FOR THE TREATMENT OF INFLAMMATION AND IMMUNE DISORDERS |
| CA2669695C (en) | 2006-11-13 | 2012-10-30 | Synta Pharmaceuticals Corp. | Tetrahydropyridinyl compounds for inflammation and immune-related uses |
| WO2008122038A1 (en) | 2007-04-02 | 2008-10-09 | President And Fellows Of Harvard College | Regulating autophagy |
| WO2008148108A1 (en) * | 2007-05-24 | 2008-12-04 | Calcimedica, Inc. | Calcium channel proteins and uses thereof |
| WO2009001214A2 (en) * | 2007-06-28 | 2008-12-31 | Pfizer Products Inc. | Thieno[2,3-d]pyrimidin-4(3h)-one, isoxazolo[5,4-d]pyrimidin-4(5h)-one and isothiazolo[5,4-d]pyrimidin-4(5h)-one derivatives as calcium receptor antagonists |
| WO2009011850A2 (en) * | 2007-07-16 | 2009-01-22 | Abbott Laboratories | Novel therapeutic compounds |
| KR101257550B1 (ko) | 2007-09-10 | 2013-04-24 | 칼시메디카, 인크 | 세포내 칼슘을 조절하는 화합물 |
| US8389567B2 (en) * | 2007-12-12 | 2013-03-05 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
| TWI392673B (zh) | 2008-08-27 | 2013-04-11 | Calcimedica Inc | 調控細胞內鈣離子濃度之化合物 |
| JP4879240B2 (ja) | 2008-09-16 | 2012-02-22 | 株式会社リコー | 発振回路、dc−dcコンバータ及び半導体装置 |
| US8524763B2 (en) | 2008-09-22 | 2013-09-03 | Calcimedica, Inc. | Inhibitors of store operated calcium release |
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2008
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- 2008-08-15 MX MX2010002712A patent/MX2010002712A/es not_active Application Discontinuation
- 2008-08-15 CA CA2699157A patent/CA2699157A1/en not_active Abandoned
- 2008-08-15 RU RU2010112967/04A patent/RU2465272C2/ru not_active IP Right Cessation
- 2008-08-15 WO PCT/US2008/073392 patent/WO2009035818A1/en not_active Ceased
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Also Published As
| Publication number | Publication date |
|---|---|
| KR101257550B1 (ko) | 2013-04-24 |
| RU2465272C2 (ru) | 2012-10-27 |
| AU2008299220A1 (en) | 2009-03-19 |
| RU2010112967A (ru) | 2011-10-20 |
| CN101854933A (zh) | 2010-10-06 |
| US20090137659A1 (en) | 2009-05-28 |
| WO2009035818A8 (en) | 2009-05-14 |
| WO2009035818A1 (en) | 2009-03-19 |
| AU2008299220B2 (en) | 2011-07-21 |
| BRPI0816326A2 (pt) | 2015-03-24 |
| MX2010002712A (es) | 2010-06-09 |
| US20120289587A1 (en) | 2012-11-15 |
| KR20100061836A (ko) | 2010-06-09 |
| EP2200607A1 (en) | 2010-06-30 |
| JP2010539083A (ja) | 2010-12-16 |
| US8524765B2 (en) | 2013-09-03 |
| EP2200607A4 (en) | 2012-02-22 |
| US8263641B2 (en) | 2012-09-11 |
| CA2699157A1 (en) | 2009-03-19 |
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| LAPS | Cancellation because of no payment of annual fees |