SI20876B - Derivati propanojske kisline, ki inhibirajo vezavo integrinov na njihove receptorje - Google Patents
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Abstract
Postopek za inhibicijo vezave alfa4beta1-integrina na njegove receptorje, npr. VCAM-1 (vaskularna celična adhezijska molekula-1) in fibronektin; spojine, ki inhibirajo to vezavo; farmacevtsko aktivni sestavki, ki obsegajo take spojine; in uporaba takih spojin, kot so bodisi zgoraj ali v formulacijah, za kontrolo ali preprečevanje bolezenskih stanj, v katere je vključen alfa4beta1.
Claims (8)
1 PATENTNI ZAHTEVKI 1. Spojina s strukturo:
kjer je obroč, ki vključuje Y, monociklični heterocikel, ki sestoji iz po izbiri substituiranega oksopiridinila s formulo IV:
IV q je celo število od 0 do 4 T je izbran iz skupine, ki jo sestavlja -(CH2)b, kjer je b celo število od 0 do 3 L je izbran iz skupine, ki jo sestavljajo -O-, -NR -, -S- in -(CH2)n, kjer je n celo število 0 ali 1, in B, R*, R4, R6, R9, R^9, R1 1 in R13 so neodvisno izbrani iz skupine, ki jo sestavljajo vodik, halogen, hidroksil, alkil, alkenil, alkinil, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkil, alifatski acil, -CF3, nitro, amino, ciano, karboksi, 2 -N(C1-C3alkil)-C(0)(CrC3alkil), -NHC(0)NH(C,-C3alkil), -NHC(0)N(C,-C3alkil)C(0)-NH(Ci-C3alkil), -Ci-C3alkilamino, alkenilamino, alkinilamino, di(C!-C3alkil)amino, -C(0)0-(CrC3)alkil, -C(0)NH-(Ci-C3)alkil, -CH=NOH, -P03H2, -0P03H2, -C(0)N(CrC3alkil)2, haloalkil, alkoksialkoksi, karboksaldehid, karboksamid, cikloalkil, cikloalkenil, cikloalkinil, cikloalkilalkil, aril, aroil, ariloksi, arilamino, biaril, tioaril, diarilamino, heterociklil, alkilaril, aralkenil, aralkil, alkilheterociklil, heterociklilalkil, sulfonil, -S02-(Ci-C3alkil), -S03-(Ci-C3alkil), sulfonamido, ariloksialkil, karboksil, karbamat in -C(0)NH(benzil), R8 je neodvisno izbran iz skupine, ki jo sestavljajo halogen, hidroksil, alkil, alkenil, alkinil, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkil, alifatski acil, -CF3, nitro, amino, ciano, karboksi, -N(C1-C3alkil)-C(0)(C1-C3alkil), -NHC(0)NH(CrC3alkil), -NHC(0)N(C i -C3alkil)C(0)-NH(C i -C3alkil), -C i -C3alkilamino, alkenilamino, alkinilamino, di(Ci-C3alkil)amino, -C(0)0-(Ci-C3alkil), -C(0)NH-(Ci- C3)alkil, -CH=NOH, -P03H2, -0P03H2, -C(0)N(Ci-C3alkil)2, haloalkil, alkoksialkoksi, karboksaldehid, karboksamid, cikloalkil, cikloalkenil, cikloalkinil, cikloalkilalkil, aril, aroil, ariloksi, arilamino, biaril, tioaril, diarilamino, heterociklil, alkilaril, aralkenil, aralkil, alkilheterociklil, heterociklilalkil, sulfonil, -S02-(Ci-C3alkil), -S03-(Ci-C3alkil), sulfonamido, ariloksialkil, karboksil, karbamat in -C(0)NH(benzil), kjer, kadar je L -NR13-, lahko R4 in R13, vzeta skupaj, tvorita obroč in kjer R6 in R8, vzeta skupaj, lahko tvorita obroč in kjer R9 in R10, vzeta skupaj, lahko tvorita obroč, ali njena farmacevtsko sprejemljiva sol.
2. Spojina po zahtevku 1, ki je derivat le-te, izbran izmed estrov, karbamatov in aminalov.
3. Spojina s strukturo: 3
kjer je krog Q obroč, ki sestoji iz:
kjer je q celo število od nič do 4 in so B, R1, R6, R8, R9, R10 in R11 vsak neodvisno izbrani iz skupine, ki jo sestavljajo vodik, halogen, hidroksil, alkil, alkenil, alkinil, alkoksi, alkenoksi, alkinoksi, tioalkoksi, hidroksialkil, alifatski acil, -CF3, nitro, amino, ciano, karboksi, -N(Ci-C3alkil)-C(0)(Ci-C3alkil), -NHC(0)NH(Ci-C3alkil), -NHC(0)N(Ci-C3alkil)C(0)-NH(CrC3alkil), -CrC3alkilamino, alkenilamino, alkinilamino, di(C1-C3alkil)amino, -C(0)0-(Ci-C3alkil), -C(0)NH-(Ci- C3)alkil, -CH=NOH, -P03H2, -0P03H2, -C(0)N(CrC3alkil)2, haloalkil, alkoksialkoksi, karboksaldehid, karboksamid, cikloalkil, cikloalkenil, cikloalkinil, cikloalkilalkil, aril, aroil, ariloksi, arilamino, biaril, tioaril, diarilamino, heterociklil, alkilaril, aralkenil, aralkil, alkilheterociklil, heterociklilalkil, sulfonil, -S02-(CrC3alkil), -S03-(Ci-C3alkil), sulfonamido, ariloksialkil, karboksil, karbamat in -C(0)NH(benzil), kjer R in R , vzeta skupaj, lahko tvorita obroč 4 in kjer R1 in R2, vzeta skupaj, lahko tvorita obroč, ali njena farmacevtsko sprejemljiva sol.
4. Spojina po zahtevku 3, ki je derivat le-te, izbran izmed estrov, karbamatov in aminalov.
5. Spojina po zahtevku 3, kjer so R6, R8, R1, R2 in R11 vsak neodvisno izbrani iz skupine, ki jo sestavljata vodik in alkil, in je R1 pri vsakem pojavljanju neodvisno izbran iz skupine, ki jo sestavljajo vodik, 2-tienilmetil, benzil in metil.
6. Spojina, izbrana iz skupine, ki jo sestavljajo (3S)-3-(l,3-benzodioksol-5-il)-3-((2R,S)-2-(3 -benzil- 5 -metil-2-okso-1 (2H)-piridinil)heksanoilamino)propanoj ska kislina, (3S)-3-( 1,3-benzodioksol-5-il)-3-((2R,S)-2-(3-(3-klorobenzil)-5-metil-2-okso-l(2H)-piridinil)heksanoilamino)propanojska kislina, (3S)-3-(l,3-benzodioksol-5-il)-3-(((2S)-2-(2-okso-3-(fenilmetil)-l-(2H)-piridinil)heksanoil)amino)propanojska kislina, (3S)-3-(l,3-benzodioksol-5-il)-3-((2-(3-klorofenil)metil)-5-metil-2-okso-l(2H)-piridinil)heksanoil)amino)propanojska kislina in njihove farmacevtsko sprejemljive soli.
7. Spojina po zahtevku 6, ki je derivat le-te, izbran iz skupine, ki jo sestavljajo estri, karbamati in aminali.
8. Farmacevtski sestavek, ki obsega spojino po zahtevku 1 v farmacevtsko sprejemljivem nosilcu. 1 Uporaba spojine po zahtevku 1 za pripravo zdravila za selektivno inhibiranje 2 vezave a4Pi-integrina pri sesalcu.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13296799P | 1999-05-07 | 1999-05-07 | |
| US17044199P | 1999-12-10 | 1999-12-10 | |
| PCT/US2000/012464 WO2000068188A1 (en) | 1999-05-07 | 2000-05-05 | Propanoic acid derivatives that inhibit the binding of integrins to their receptors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SI20876A SI20876A (sl) | 2002-10-31 |
| SI20876B true SI20876B (sl) | 2009-08-31 |
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| Application Number | Title | Priority Date | Filing Date |
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| SI200020020A SI20876B (sl) | 1999-05-07 | 2000-05-05 | Derivati propanojske kisline, ki inhibirajo vezavo integrinov na njihove receptorje |
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| Country | Link |
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| EP (1) | EP1189881B2 (sl) |
| JP (2) | JP4841729B2 (sl) |
| KR (1) | KR100767199B1 (sl) |
| CN (1) | CN100360499C (sl) |
| AT (1) | ATE277923T1 (sl) |
| AU (1) | AU4826900A (sl) |
| BR (1) | BR0010349B1 (sl) |
| CA (1) | CA2373180C (sl) |
| CZ (1) | CZ304225B6 (sl) |
| DE (1) | DE60014369T3 (sl) |
| ES (1) | ES2228527T5 (sl) |
| HK (1) | HK1044533A1 (sl) |
| HU (1) | HU229155B1 (sl) |
| IL (2) | IL146312A0 (sl) |
| MX (1) | MXPA01011341A (sl) |
| NO (1) | NO329899B1 (sl) |
| NZ (1) | NZ515249A (sl) |
| RO (1) | RO121640B1 (sl) |
| RU (1) | RU2255933C9 (sl) |
| SI (1) | SI20876B (sl) |
| SK (1) | SK288186B6 (sl) |
| TR (1) | TR200103427T2 (sl) |
| WO (1) | WO2000068188A1 (sl) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6723711B2 (en) * | 1999-05-07 | 2004-04-20 | Texas Biotechnology Corporation | Propanoic acid derivatives that inhibit the binding of integrins to their receptors |
| US6972296B2 (en) | 1999-05-07 | 2005-12-06 | Encysive Pharmaceuticals Inc. | Carboxylic acid derivatives that inhibit the binding of integrins to their receptors |
| AR026748A1 (es) | 1999-12-08 | 2003-02-26 | Vertex Pharma | Un compuesto inhibidor de caspasas, una composicion farmaceutica que lo comprende, un metodo para la sintesis del mismo y un compuesto intermediario paradicha sintesis |
| AR030817A1 (es) * | 2000-10-02 | 2003-09-03 | Novartis Ag | Derivados de diazacicloalcanodiona |
| AU2003248758A1 (en) | 2002-06-28 | 2004-01-19 | Vertex Pharmaceuticals Incorporated | Caspase inhibitors and uses thereof |
| AU2003265398A1 (en) | 2002-08-09 | 2004-02-25 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds and methods to modulate coagulation |
| TW200500343A (en) | 2002-12-20 | 2005-01-01 | Vertex Pharma | Caspase inhibitors and uses thereof |
| PE20050159A1 (es) | 2003-05-27 | 2005-04-19 | Vertex Pharma | Derivados de acido 3-[2-(3-amino-2-oxo-2h-piridin-1-il)-acetilamino]-4-oxo-pentanoico como inhibidores de caspasa |
| US7501538B2 (en) | 2003-08-08 | 2009-03-10 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions and methods of use |
| CN1832920A (zh) | 2003-08-08 | 2006-09-13 | 特兰斯泰克制药公司 | 芳基和杂芳基化合物,组合物及其使用方法 |
| US7208601B2 (en) | 2003-08-08 | 2007-04-24 | Mjalli Adnan M M | Aryl and heteroaryl compounds, compositions, and methods of use |
| WO2006053342A2 (en) * | 2004-11-12 | 2006-05-18 | Osi Pharmaceuticals, Inc. | Integrin antagonists useful as anticancer agents |
| SI1928454T1 (sl) | 2005-05-10 | 2015-01-30 | Intermune, Inc. | Piridonski derivati za moduliranje s stresom aktiviranega protein kinaznega sistema |
| PE20070505A1 (es) | 2005-07-11 | 2007-05-15 | Wyeth Corp | Inhibidores de glutamato de metaloproteinasas de matriz y agrecanasas |
| GT200600305A (es) | 2005-10-13 | 2007-02-26 | Métodos para preparar derivados de acido glutamico | |
| JP5627574B2 (ja) | 2008-06-03 | 2014-11-19 | インターミューン， インコーポレイテッド | 炎症性および線維性疾患を治療するための化合物および方法 |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| KR102373700B1 (ko) | 2014-04-02 | 2022-03-11 | 인터뮨, 인크. | 항섬유성 피리디논 |
| US10875875B2 (en) * | 2017-04-26 | 2020-12-29 | Aviara Pharmaceuticals, Inc. | Propionic acid derivatives and methods of use thereof |
| AR114489A1 (es) * | 2018-04-12 | 2020-09-09 | Morphic Therapeutic Inc | ANTAGONISTAS DE LA INTEGRINA a4b7 HUMANA |
| JP7437495B2 (ja) * | 2019-10-16 | 2024-02-22 | モーフィック セラピューティック，インコーポレイテッド | ヒトインテグリンα４β７の阻害 |
| WO2023134698A1 (zh) * | 2022-01-11 | 2023-07-20 | 深圳信立泰药业股份有限公司 | 一种哒嗪-1(6h)-6-氧代类化合物及其制备方法与应用 |
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|---|---|---|---|---|
| US5874424A (en) * | 1995-12-20 | 1999-02-23 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1β converting enzyme |
| HUT68769A (en) * | 1991-05-07 | 1995-07-28 | Merck & Co Inc | FIBRINOGéN RECEPTOR ANTAGONIST COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM AS EFFECTIVE SUBSTANCE |
| US5847135A (en) * | 1994-06-17 | 1998-12-08 | Vertex Pharmaceuticals, Incorporated | Inhibitors of interleukin-1β converting enzyme |
| EP0761680A3 (en) * | 1995-09-12 | 1999-05-06 | Ono Pharmaceutical Co., Ltd. | Tetrazole compounds having Interleukin-1beta converting enzyme inhibitory activity |
| EP0917462B1 (en) * | 1996-07-25 | 2006-09-13 | Biogen Idec MA Inc. | Cell adhesion inhibitors |
| AU724191B2 (en) * | 1996-08-29 | 2000-09-14 | Merck & Co., Inc. | Integrin antagonists |
| EP0932598A1 (en) * | 1996-10-11 | 1999-08-04 | Warner-Lambert Company | ASPARTATE ESTER INHIBITORS OF INTERLEUKIN-1$g(b) CONVERTING ENZYME |
| DE19647380A1 (de) * | 1996-11-15 | 1998-05-20 | Hoechst Ag | 5-Ring-Heterocyclen als Inhibitoren der Leukozytenadhäsion und VLA-4-Antagonisten |
| AR016751A1 (es) * | 1996-11-22 | 2001-08-01 | Athena Neurosciences Inc | Metodo para inhibir la liberacion del peptido beta-amiloide en una celula, composicion farmaceutica y compuestos utiles en dicho metodo |
| RU2183642C2 (ru) * | 1997-05-02 | 2002-06-20 | Акцо Нобель Н.В. | Ингибиторы сериновых протеаз |
| DE19741235A1 (de) * | 1997-09-18 | 1999-03-25 | Hoechst Marion Roussel De Gmbh | Neue Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
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| WO2000061631A1 (en) * | 1999-04-12 | 2000-10-19 | Astrazeneca Ab | Modified pentapeptide antagonists of the atrial natriuretic peptide clearance receptor |
-
2000
- 2000-05-05 TR TR2001/03427T patent/TR200103427T2/xx unknown
- 2000-05-05 BR BRPI0010349-7A patent/BR0010349B1/pt not_active IP Right Cessation
- 2000-05-05 SI SI200020020A patent/SI20876B/sl not_active IP Right Cessation
- 2000-05-05 EP EP00930450A patent/EP1189881B2/en not_active Expired - Lifetime
- 2000-05-05 RO ROA200101209A patent/RO121640B1/ro unknown
- 2000-05-05 HU HU0202184A patent/HU229155B1/hu not_active IP Right Cessation
- 2000-05-05 CN CNB00809957XA patent/CN100360499C/zh not_active Expired - Fee Related
- 2000-05-05 DE DE60014369T patent/DE60014369T3/de not_active Expired - Lifetime
- 2000-05-05 CZ CZ2001-3983A patent/CZ304225B6/cs not_active IP Right Cessation
- 2000-05-05 WO PCT/US2000/012464 patent/WO2000068188A1/en active IP Right Grant
- 2000-05-05 ES ES00930450T patent/ES2228527T5/es not_active Expired - Lifetime
- 2000-05-05 CA CA002373180A patent/CA2373180C/en not_active Expired - Fee Related
- 2000-05-05 KR KR1020017014179A patent/KR100767199B1/ko not_active IP Right Cessation
- 2000-05-05 RU RU2001133341/04A patent/RU2255933C9/ru not_active IP Right Cessation
- 2000-05-05 AU AU48269/00A patent/AU4826900A/en not_active Abandoned
- 2000-05-05 MX MXPA01011341A patent/MXPA01011341A/es active IP Right Grant
- 2000-05-05 AT AT00930450T patent/ATE277923T1/de not_active IP Right Cessation
- 2000-05-05 JP JP2000617169A patent/JP4841729B2/ja not_active Expired - Fee Related
- 2000-05-05 SK SK1609-2001A patent/SK288186B6/sk not_active IP Right Cessation
- 2000-05-05 NZ NZ515249A patent/NZ515249A/en not_active IP Right Cessation
- 2000-05-05 IL IL14631200A patent/IL146312A0/xx unknown
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2001
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- 2001-11-06 NO NO20015419A patent/NO329899B1/no not_active IP Right Cessation
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2002
- 2002-08-23 HK HK02106258.2A patent/HK1044533A1/zh unknown
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2011
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Effective date: 20090604 |
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