JP2006511612A5 - - Google Patents
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- Publication number
- JP2006511612A5 JP2006511612A5 JP2005502649A JP2005502649A JP2006511612A5 JP 2006511612 A5 JP2006511612 A5 JP 2006511612A5 JP 2005502649 A JP2005502649 A JP 2005502649A JP 2005502649 A JP2005502649 A JP 2005502649A JP 2006511612 A5 JP2006511612 A5 JP 2006511612A5
- Authority
- JP
- Japan
- Prior art keywords
- benzoxazole
- carboxy
- compound
- pharmaceutically acceptable
- acceptable salt
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims 66
- 150000003839 salts Chemical class 0.000 claims 58
- 108010071690 Prealbumin Proteins 0.000 claims 48
- 102000009190 Transthyretin Human genes 0.000 claims 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 33
- 206010002022 amyloidosis Diseases 0.000 claims 21
- 238000000034 method Methods 0.000 claims 21
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical class C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 claims 15
- 206010007509 Cardiac amyloidosis Diseases 0.000 claims 11
- -1 2,6-difluorophenyl Chemical group 0.000 claims 8
- 238000010494 dissociation reaction Methods 0.000 claims 8
- 230000005593 dissociations Effects 0.000 claims 8
- 150000003071 polychlorinated biphenyls Chemical group 0.000 claims 8
- 208000034846 Familial Amyloid Neuropathies Diseases 0.000 claims 6
- 206010019889 Hereditary neuropathic amyloidosis Diseases 0.000 claims 6
- 229960000616 diflunisal Drugs 0.000 claims 6
- 230000000694 effects Effects 0.000 claims 6
- 201000007905 transthyretin amyloidosis Diseases 0.000 claims 6
- 239000003814 drug Substances 0.000 claims 5
- 210000004185 liver Anatomy 0.000 claims 5
- 238000002054 transplantation Methods 0.000 claims 5
- 208000027121 wild type ATTR amyloidosis Diseases 0.000 claims 5
- PMIIYXSRUSULDH-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)-1,3-benzoxazole-4-carboxylic acid Chemical compound N=1C=2C(C(=O)O)=CC=CC=2OC=1C1=C(Cl)C=CC=C1Cl PMIIYXSRUSULDH-UHFFFAOYSA-N 0.000 claims 4
- VTTCWUHZUXWTPP-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)-1,3-benzoxazole-5-carboxylic acid Chemical compound N=1C2=CC(C(=O)O)=CC=C2OC=1C1=C(Cl)C=CC=C1Cl VTTCWUHZUXWTPP-UHFFFAOYSA-N 0.000 claims 4
- XVNRKPCHMYOPPL-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid Chemical compound O1C2=CC(C(=O)O)=CC=C2N=C1C1=C(Cl)C=CC=C1Cl XVNRKPCHMYOPPL-UHFFFAOYSA-N 0.000 claims 4
- QMACGJYSQKQXKH-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)-1,3-benzoxazole-7-carboxylic acid Chemical compound O1C=2C(C(=O)O)=CC=CC=2N=C1C1=C(Cl)C=CC=C1Cl QMACGJYSQKQXKH-UHFFFAOYSA-N 0.000 claims 4
- SYQQJVHDLFNSNY-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-1,3-benzoxazole-4-carboxylic acid Chemical compound N=1C=2C(C(=O)O)=CC=CC=2OC=1C1=C(F)C=CC=C1F SYQQJVHDLFNSNY-UHFFFAOYSA-N 0.000 claims 4
- DLUAYZFBDZUTPO-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-1,3-benzoxazole-5-carboxylic acid Chemical compound N=1C2=CC(C(=O)O)=CC=C2OC=1C1=C(F)C=CC=C1F DLUAYZFBDZUTPO-UHFFFAOYSA-N 0.000 claims 4
- VMEKBDFJIXVYME-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-1,3-benzoxazole-6-carboxylic acid Chemical compound O1C2=CC(C(=O)O)=CC=C2N=C1C1=C(F)C=CC=C1F VMEKBDFJIXVYME-UHFFFAOYSA-N 0.000 claims 4
- UBHVVKLDLAIMBG-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-1,3-benzoxazole-7-carboxylic acid Chemical compound O1C=2C(C(=O)O)=CC=CC=2N=C1C1=C(F)C=CC=C1F UBHVVKLDLAIMBG-UHFFFAOYSA-N 0.000 claims 4
- MQKHRHQZBRWEJP-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-1,3-benzoxazole-4-carboxylic acid Chemical compound N=1C=2C(C(=O)O)=CC=CC=2OC=1C1=CC(Cl)=CC(Cl)=C1 MQKHRHQZBRWEJP-UHFFFAOYSA-N 0.000 claims 4
- UGNMVUZMIXYKPW-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-1,3-benzoxazole-5-carboxylic acid Chemical compound N=1C2=CC(C(=O)O)=CC=C2OC=1C1=CC(Cl)=CC(Cl)=C1 UGNMVUZMIXYKPW-UHFFFAOYSA-N 0.000 claims 4
- ZTDDXZWJHRTEDF-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-1,3-benzoxazole-7-carboxylic acid Chemical compound O1C=2C(C(=O)O)=CC=CC=2N=C1C1=CC(Cl)=CC(Cl)=C1 ZTDDXZWJHRTEDF-UHFFFAOYSA-N 0.000 claims 4
- GLYCSRRIYCGKIR-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-1,3-benzoxazole-4-carboxylic acid Chemical compound N=1C=2C(C(=O)O)=CC=CC=2OC=1C1=CC(F)=CC(F)=C1 GLYCSRRIYCGKIR-UHFFFAOYSA-N 0.000 claims 4
- GAKAUTDPZCHUQY-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-1,3-benzoxazole-5-carboxylic acid Chemical compound N=1C2=CC(C(=O)O)=CC=C2OC=1C1=CC(F)=CC(F)=C1 GAKAUTDPZCHUQY-UHFFFAOYSA-N 0.000 claims 4
- RVLUUNWNVBRPED-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-1,3-benzoxazole-6-carboxylic acid Chemical compound O1C2=CC(C(=O)O)=CC=C2N=C1C1=CC(F)=CC(F)=C1 RVLUUNWNVBRPED-UHFFFAOYSA-N 0.000 claims 4
- JHHHICSUIPNPOX-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-1,3-benzoxazole-7-carboxylic acid Chemical compound O1C=2C(C(=O)O)=CC=CC=2N=C1C1=CC(F)=CC(F)=C1 JHHHICSUIPNPOX-UHFFFAOYSA-N 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- TXEIIPDJKFWEEC-UHFFFAOYSA-N tafamidis Chemical compound O1C2=CC(C(=O)O)=CC=C2N=C1C1=CC(Cl)=CC(Cl)=C1 TXEIIPDJKFWEEC-UHFFFAOYSA-N 0.000 claims 4
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 claims 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims 3
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 claims 3
- JRUHAIBYXWRVJA-UHFFFAOYSA-N 2-phenyl-1,3-benzoxazole-4-carboxylic acid Chemical compound N=1C=2C(C(=O)O)=CC=CC=2OC=1C1=CC=CC=C1 JRUHAIBYXWRVJA-UHFFFAOYSA-N 0.000 claims 2
- UNJLCBQGDIBMAE-UHFFFAOYSA-N 2-phenyl-1,3-benzoxazole-5-carboxylic acid Chemical compound N=1C2=CC(C(=O)O)=CC=C2OC=1C1=CC=CC=C1 UNJLCBQGDIBMAE-UHFFFAOYSA-N 0.000 claims 2
- ICSRYAQXSYGQSJ-UHFFFAOYSA-N 2-phenyl-1,3-benzoxazole-6-carboxylic acid Chemical compound O1C2=CC(C(=O)O)=CC=C2N=C1C1=CC=CC=C1 ICSRYAQXSYGQSJ-UHFFFAOYSA-N 0.000 claims 2
- RZZURKQUMZPYIZ-UHFFFAOYSA-N 2-phenyl-1,3-benzoxazole-7-carboxylic acid Chemical compound O1C=2C(C(=O)O)=CC=CC=2N=C1C1=CC=CC=C1 RZZURKQUMZPYIZ-UHFFFAOYSA-N 0.000 claims 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical group CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims 2
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims 2
- 210000001124 body fluid Anatomy 0.000 claims 2
- 239000010839 body fluid Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000006641 stabilisation Effects 0.000 claims 2
- 238000011105 stabilization Methods 0.000 claims 2
- 230000004913 activation Effects 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 230000000368 destabilizing effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 102200150628 rs151220873 Human genes 0.000 claims 1
- 102200049725 rs182983506 Human genes 0.000 claims 1
- 238000012216 screening Methods 0.000 claims 1
- 150000003384 small molecules Chemical class 0.000 claims 1
- 230000000087 stabilizing effect Effects 0.000 claims 1
- 230000007704 transition Effects 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43507902P | 2002-12-19 | 2002-12-19 | |
| US46543503P | 2003-04-24 | 2003-04-24 | |
| PCT/US2003/040567 WO2004056315A2 (en) | 2002-12-19 | 2003-12-19 | Compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010162800A Division JP2010270134A (ja) | 2002-12-19 | 2010-07-20 | トランスチレチンの安定化及びトランスチレチンの誤った折り畳みの阻害のための組成物及び方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2006511612A JP2006511612A (ja) | 2006-04-06 |
| JP2006511612A5 true JP2006511612A5 (https=) | 2008-06-19 |
| JP4665076B2 JP4665076B2 (ja) | 2011-04-06 |
Family
ID=32685364
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2005502649A Expired - Lifetime JP4665076B2 (ja) | 2002-12-19 | 2003-12-19 | トランスチレチンの安定化及びトランスチレチンの誤った折り畳みの阻害のための組成物及び方法 |
| JP2010162800A Pending JP2010270134A (ja) | 2002-12-19 | 2010-07-20 | トランスチレチンの安定化及びトランスチレチンの誤った折り畳みの阻害のための組成物及び方法 |
| JP2013170867A Expired - Lifetime JP5756151B2 (ja) | 2002-12-19 | 2013-08-21 | トランスチレチンの安定化及びトランスチレチンの誤った折り畳みの阻害のための組成物及び方法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010162800A Pending JP2010270134A (ja) | 2002-12-19 | 2010-07-20 | トランスチレチンの安定化及びトランスチレチンの誤った折り畳みの阻害のための組成物及び方法 |
| JP2013170867A Expired - Lifetime JP5756151B2 (ja) | 2002-12-19 | 2013-08-21 | トランスチレチンの安定化及びトランスチレチンの誤った折り畳みの阻害のための組成物及び方法 |
Country Status (20)
| Country | Link |
|---|---|
| US (6) | US7214695B2 (https=) |
| EP (3) | EP2325651B1 (https=) |
| JP (3) | JP4665076B2 (https=) |
| KR (1) | KR101089904B1 (https=) |
| CN (2) | CN101413143B (https=) |
| AT (2) | ATE405840T1 (https=) |
| AU (2) | AU2003303196C1 (https=) |
| BE (1) | BE2012C008I2 (https=) |
| BR (1) | BRPI0317463B8 (https=) |
| CA (2) | CA2800237C (https=) |
| CY (2) | CY1108467T1 (https=) |
| DE (2) | DE60323155D1 (https=) |
| DK (2) | DK1988397T3 (https=) |
| ES (3) | ES2312857T7 (https=) |
| FI (1) | FI1587821T6 (https=) |
| FR (1) | FR12C0008I2 (https=) |
| LU (1) | LU91935I2 (https=) |
| PT (2) | PT1587821E (https=) |
| SI (1) | SI1587821T2 (https=) |
| WO (1) | WO2004056315A2 (https=) |
Families Citing this family (96)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06105459B2 (ja) * | 1988-08-11 | 1994-12-21 | 日本電気株式会社 | ベクトル処理装置 |
| CA2800237C (en) * | 2002-12-19 | 2016-05-17 | The Scripps Research Institute | Compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding |
| US7279457B2 (en) * | 2004-03-12 | 2007-10-09 | Biodel, Inc. | Rapid acting drug delivery compositions |
| WO2005113523A1 (en) | 2004-05-20 | 2005-12-01 | Foldrx Pharmaceuticals, Inc. | 2-((hetero) aryl)-benzoxazole compounds and derivatives, compositions and methods for stabilizing transthyretin and inhibiting transthyretin misfolding |
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| EP1921916A2 (en) * | 2005-08-11 | 2008-05-21 | The Scripps Research Institute | Genistein inhibition of transthyretin amyloidosis |
| WO2008034016A2 (en) * | 2006-09-15 | 2008-03-20 | Foldrx Pharmaceuticals, Inc. | Assays for detecting native-state proteins and identifying compounds that modulate the stability of native-state proteins |
| WO2010054127A1 (en) * | 2008-11-05 | 2010-05-14 | Elan Pharmaceuticals, Inc. | Methods and agents for stabilizing non-pathological amyloidogenic polypeptides |
| TWI720517B (zh) | 2009-01-15 | 2021-03-01 | 美商英塞特公司 | 製造ｊａｋ抑制劑之方法及相關中間化合物 |
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