ZA200308024B - Inhibitors of integrin alphavbeta6. - Google Patents
Inhibitors of integrin alphavbeta6. Download PDFInfo
- Publication number
- ZA200308024B ZA200308024B ZA200308024A ZA200308024A ZA200308024B ZA 200308024 B ZA200308024 B ZA 200308024B ZA 200308024 A ZA200308024 A ZA 200308024A ZA 200308024 A ZA200308024 A ZA 200308024A ZA 200308024 B ZA200308024 B ZA 200308024B
- Authority
- ZA
- South Africa
- Prior art keywords
- pyridin
- ylamino
- propionic acid
- biphenyl
- butanoylamino
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title claims description 9
- 108010004788 integrin alphavbeta6 Proteins 0.000 title description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 376
- 235000019260 propionic acid Nutrition 0.000 claims description 188
- -1 pyridin-2-ylamino Chemical group 0.000 claims description 82
- 150000001875 compounds Chemical class 0.000 claims description 65
- 108010044426 integrins Proteins 0.000 claims description 50
- 102000006495 integrins Human genes 0.000 claims description 50
- 125000006239 protecting group Chemical group 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 239000012453 solvate Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000003277 amino group Chemical group 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 230000004761 fibrosis Effects 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
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- 239000004480 active ingredient Substances 0.000 claims description 6
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
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- FNDSFJFNWGELLU-SSYAZFEXSA-N 3-[[(2s)-3-(acetamidomethylsulfanyl)-2-[5-(pyridin-2-ylamino)pentanoylamino]propanoyl]amino]-3-(4-phenylphenyl)propanoic acid Chemical compound N([C@H](CSCNC(=O)C)C(=O)NC(CC(O)=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)C(=O)CCCCNC1=CC=CC=N1 FNDSFJFNWGELLU-SSYAZFEXSA-N 0.000 claims description 2
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- IAVZHVRNCXXFIQ-MBMZGMDYSA-N 3-[[(2s)-6-(carbamoylamino)-2-[6-(pyridin-2-ylamino)hexanoylamino]hexanoyl]amino]-3-(4-phenylphenyl)propanoic acid Chemical compound N([C@@H](CCCCNC(=O)N)C(=O)NC(CC(O)=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)C(=O)CCCCCNC1=CC=CC=N1 IAVZHVRNCXXFIQ-MBMZGMDYSA-N 0.000 claims description 2
- YKTPPPDELUIVHI-QBHOUYDASA-N 3-[[(2s)-6-amino-2-[5-(pyridin-2-ylamino)pentanoylamino]hexanoyl]amino]-3-(4-phenylphenyl)propanoic acid Chemical compound N([C@@H](CCCCN)C(=O)NC(CC(O)=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)C(=O)CCCCNC1=CC=CC=N1 YKTPPPDELUIVHI-QBHOUYDASA-N 0.000 claims description 2
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- YZXXIKCLBLMVTJ-IKOFQBKESA-N (4r)-5-[[2-carboxy-1-(4-phenylphenyl)ethyl]amino]-5-oxo-4-[5-(pyridin-2-ylamino)pentanoylamino]pentanoic acid Chemical compound N([C@H](CCC(=O)O)C(=O)NC(CC(O)=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)C(=O)CCCCNC1=CC=CC=N1 YZXXIKCLBLMVTJ-IKOFQBKESA-N 0.000 claims 1
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- BPBNVJUUBUTFCD-UHFFFAOYSA-N 3-(3-bromophenyl)-3-[[3-phenylmethoxy-2-[5-(pyridin-2-ylamino)pentanoylamino]propanoyl]amino]propanoic acid Chemical compound C=1C=CC(Br)=CC=1C(CC(=O)O)NC(=O)C(NC(=O)CCCCNC=1N=CC=CC=1)COCC1=CC=CC=C1 BPBNVJUUBUTFCD-UHFFFAOYSA-N 0.000 claims 1
- QILMETWBQMEBAZ-UHFFFAOYSA-N 3-(3-chlorophenyl)-3-[[3-phenylmethoxy-2-[5-(pyridin-2-ylamino)pentanoylamino]propanoyl]amino]propanoic acid Chemical compound C=1C=CC(Cl)=CC=1C(CC(=O)O)NC(=O)C(NC(=O)CCCCNC=1N=CC=CC=1)COCC1=CC=CC=C1 QILMETWBQMEBAZ-UHFFFAOYSA-N 0.000 claims 1
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- DJBGPUVXNUYDND-CGHJUBPDSA-N 3-(4-phenylphenyl)-3-[[(2r)-2-[5-(pyridin-2-ylamino)pentanoylamino]propanoyl]amino]propanoic acid Chemical compound N([C@H](C)C(=O)NC(CC(O)=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)C(=O)CCCCNC1=CC=CC=N1 DJBGPUVXNUYDND-CGHJUBPDSA-N 0.000 claims 1
- OUEDEYHFICOQAL-VCHQGTEKSA-N 3-(4-phenylphenyl)-3-[[(2r)-2-phenyl-2-[5-(pyridin-2-ylamino)pentanoylamino]acetyl]amino]propanoic acid Chemical compound N([C@@H](C(=O)NC(CC(=O)O)C=1C=CC(=CC=1)C=1C=CC=CC=1)C=1C=CC=CC=1)C(=O)CCCCNC1=CC=CC=N1 OUEDEYHFICOQAL-VCHQGTEKSA-N 0.000 claims 1
- AIODABPXAVUICN-BDCODIICSA-N 3-(4-phenylphenyl)-3-[[(2r)-3-phenyl-2-[5-(pyridin-2-ylamino)pentanoylamino]propanoyl]amino]propanoic acid Chemical compound C([C@H](C(=O)NC(CC(=O)O)C=1C=CC(=CC=1)C=1C=CC=CC=1)NC(=O)CCCCNC=1N=CC=CC=1)C1=CC=CC=C1 AIODABPXAVUICN-BDCODIICSA-N 0.000 claims 1
- HWAMMTZNTCKXIB-PUOOBJKZSA-N 3-(4-phenylphenyl)-3-[[(2s)-2-[4-(pyridin-2-ylamino)butanoylamino]-3-tritylsulfanylpropanoyl]amino]propanoic acid Chemical compound C([C@H](C(=O)NC(CC(=O)O)C=1C=CC(=CC=1)C=1C=CC=CC=1)NC(=O)CCCNC=1N=CC=CC=1)SC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 HWAMMTZNTCKXIB-PUOOBJKZSA-N 0.000 claims 1
- DJBGPUVXNUYDND-QHELBMECSA-N 3-(4-phenylphenyl)-3-[[(2s)-2-[5-(pyridin-2-ylamino)pentanoylamino]propanoyl]amino]propanoic acid Chemical compound N([C@@H](C)C(=O)NC(CC(O)=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)C(=O)CCCCNC1=CC=CC=N1 DJBGPUVXNUYDND-QHELBMECSA-N 0.000 claims 1
- AIODABPXAVUICN-ZSXSBBPPSA-N 3-(4-phenylphenyl)-3-[[(2s)-3-phenyl-2-[5-(pyridin-2-ylamino)pentanoylamino]propanoyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)NC(CC(=O)O)C=1C=CC(=CC=1)C=1C=CC=CC=1)NC(=O)CCCCNC=1N=CC=CC=1)C1=CC=CC=C1 AIODABPXAVUICN-ZSXSBBPPSA-N 0.000 claims 1
- VINDNIBCWUZHNG-DYJLHVNUSA-N 3-(4-phenylphenyl)-3-[sulfanyl-[(2s)-5,5,5-triphenyl-2-[4-(pyridin-2-ylamino)butanoylamino]pentanoyl]amino]propanoic acid Chemical compound C([C@@H](C(=O)N(S)C(CC(=O)O)C=1C=CC(=CC=1)C=1C=CC=CC=1)NC(=O)CCCNC=1N=CC=CC=1)CC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 VINDNIBCWUZHNG-DYJLHVNUSA-N 0.000 claims 1
- FZPSMXJOSFPGSK-YPJJGMIRSA-N 3-[[(2r)-3-cyclohexyl-2-[4-(pyridin-2-ylamino)butanoylamino]propanoyl]amino]-3-(4-phenylphenyl)propanoic acid Chemical compound C([C@H](C(=O)NC(CC(=O)O)C=1C=CC(=CC=1)C=1C=CC=CC=1)NC(=O)CCCNC=1N=CC=CC=1)C1CCCCC1 FZPSMXJOSFPGSK-YPJJGMIRSA-N 0.000 claims 1
- VDDPDNSCNONJFV-OZAIVSQSSA-N 3-[[(2r)-3-hydroxy-2-[4-(pyridin-2-ylamino)butanoylamino]propanoyl]amino]-3-(4-phenylphenyl)propanoic acid Chemical compound N([C@H](CO)C(=O)NC(CC(O)=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)C(=O)CCCNC1=CC=CC=N1 VDDPDNSCNONJFV-OZAIVSQSSA-N 0.000 claims 1
- REJVOUKDMBDPGM-MIHMCVIASA-N 3-[[(2r)-4-hydroxy-2-[4-(pyridin-2-ylamino)butanoylamino]butanoyl]amino]-3-(4-phenylphenyl)propanoic acid Chemical compound N([C@H](CCO)C(=O)NC(CC(O)=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)C(=O)CCCNC1=CC=CC=N1 REJVOUKDMBDPGM-MIHMCVIASA-N 0.000 claims 1
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- ARAXKGCCMWKXJQ-MIHMCVIASA-N 3-[[(2r)-5-amino-5-oxo-2-[4-(pyridin-2-ylamino)butanoylamino]pentanoyl]amino]-3-(4-phenylphenyl)propanoic acid Chemical compound N([C@H](CCC(=O)N)C(=O)NC(CC(O)=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)C(=O)CCCNC1=CC=CC=N1 ARAXKGCCMWKXJQ-MIHMCVIASA-N 0.000 claims 1
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Classifications
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- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10112771A DE10112771A1 (de) | 2001-03-16 | 2001-03-16 | Inhibitoren des Integrins alpha¶v¶beta¶6¶ |
Publications (1)
| Publication Number | Publication Date |
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| ZA200308024B true ZA200308024B (en) | 2005-01-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| ZA200308024A ZA200308024B (en) | 2001-03-16 | 2003-10-15 | Inhibitors of integrin alphavbeta6. |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US7632951B2 (de) |
| EP (1) | EP1377540B1 (de) |
| JP (1) | JP4327461B2 (de) |
| CN (1) | CN1582271A (de) |
| AT (1) | ATE416157T1 (de) |
| AU (1) | AU2002254900B2 (de) |
| CA (1) | CA2440644C (de) |
| DE (2) | DE10112771A1 (de) |
| ES (1) | ES2316556T3 (de) |
| HU (1) | HUP0303514A2 (de) |
| MX (1) | MXPA03008215A (de) |
| WO (1) | WO2002074730A1 (de) |
| ZA (1) | ZA200308024B (de) |
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| JP4750701B2 (ja) * | 2003-07-07 | 2011-08-17 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | マロンアミド誘導体 |
| CA2540730C (en) * | 2003-10-01 | 2012-08-21 | Merck Patent Gmbh | Alfavbeta3 and alfavbeta6 integrin antagonists as antifibrotic agents |
| US20070043078A1 (en) * | 2003-10-10 | 2007-02-22 | Kowa Co., Ltd. | Angiogenesis inhibitor |
| AU2005251745A1 (en) * | 2004-06-04 | 2005-12-22 | The Regents Of The University Of California | Compounds having activity in increasing ion transport by mutant-CFTR and uses thereof |
| WO2006089114A2 (en) * | 2005-02-17 | 2006-08-24 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for treating an anthrax toxin mediated condition |
| WO2009048541A2 (en) * | 2007-10-05 | 2009-04-16 | Purdue Research Foundation | Compounds and methods for use in treating neoplasia and cancer |
| WO2009051910A1 (en) * | 2007-10-16 | 2009-04-23 | The Regents Of The University Of California | Compounds having activity in increasing ion transport by mutant-cftr and uses thereof |
| EP2217238B1 (de) | 2007-11-08 | 2014-03-12 | The General Hospital Corporation | Verfahren und zusammensetzungen zur behandlung von erkrankungen im zusammenhang mit proteinurie |
| GB0922014D0 (en) * | 2009-12-17 | 2010-02-03 | Ge Healthcare Ltd | Novel integrin binders |
| WO2013016531A2 (en) * | 2011-07-26 | 2013-01-31 | Purdue Research Foundation | Compounds and methods for use in treating neoplasia and cancer |
| GB201305668D0 (en) * | 2013-03-28 | 2013-05-15 | Glaxosmithkline Ip Dev Ltd | Avs6 Integrin Antagonists |
| WO2015179823A2 (en) * | 2014-05-23 | 2015-11-26 | The California Institute For Biomedical Research | Lung localized inhibitors of alpha(v)beta 6 |
| GB201417094D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417011D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417018D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417002D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| US20180110762A1 (en) * | 2015-03-26 | 2018-04-26 | Merck Sharp & Dohme Corp | Compositions Methods for Treating Chronic Kidney Disease |
| GB201604680D0 (en) | 2016-03-21 | 2016-05-04 | Glaxosmithkline Ip Dev Ltd | Chemical Compounds |
| EP3558303A4 (de) | 2016-12-23 | 2020-07-29 | Pliant Therapeutics, Inc. | Aminosäureverbindungen und verfahren zur verwendung |
| KR102605460B1 (ko) | 2017-02-28 | 2023-11-22 | 모픽 테라퓨틱, 인코포레이티드 | αvβ6 인테그린 억제제 |
| MA47692A (fr) | 2017-02-28 | 2020-01-08 | Morphic Therapeutic Inc | Inhibiteurs de l'intégrine (alpha-v) (bêta-6) |
| WO2020047239A1 (en) | 2018-08-29 | 2020-03-05 | Morphic Therapeutic, Inc. | INHIBITING αV β6 INTEGRIN |
| WO2022221144A1 (en) * | 2021-04-12 | 2022-10-20 | University Of Washington | Engineered peptides for αvβ6 integrin binding and related methods of use and synthesis |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6306840B1 (en) * | 1995-01-23 | 2001-10-23 | Biogen, Inc. | Cell adhesion inhibitors |
| DK1153014T3 (da) * | 1999-02-20 | 2005-01-24 | Merck Patent Gmbh | Beta-alaninderivater |
| DE10041423A1 (de) | 2000-08-23 | 2002-03-07 | Merck Patent Gmbh | Biphenylderivate |
| DE10204789A1 (de) * | 2002-02-06 | 2003-08-14 | Merck Patent Gmbh | Inhibitoren des Integrins alpha¶v¶beta6 |
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2001
- 2001-03-16 DE DE10112771A patent/DE10112771A1/de not_active Withdrawn
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- 2002-02-21 WO PCT/EP2002/001836 patent/WO2002074730A1/en active Application Filing
- 2002-02-21 MX MXPA03008215A patent/MXPA03008215A/es unknown
- 2002-02-21 CN CNA028067061A patent/CN1582271A/zh active Pending
- 2002-02-21 ES ES02724175T patent/ES2316556T3/es not_active Expired - Lifetime
- 2002-02-21 HU HU0303514A patent/HUP0303514A2/hu unknown
- 2002-02-21 EP EP02724175A patent/EP1377540B1/de not_active Expired - Lifetime
- 2002-02-21 CA CA2440644A patent/CA2440644C/en not_active Expired - Fee Related
- 2002-02-21 AU AU2002254900A patent/AU2002254900B2/en not_active Ceased
- 2002-02-21 DE DE60230127T patent/DE60230127D1/de not_active Expired - Lifetime
- 2002-02-21 JP JP2002573739A patent/JP4327461B2/ja not_active Expired - Fee Related
- 2002-02-21 US US10/471,836 patent/US7632951B2/en not_active Expired - Fee Related
- 2002-02-21 AT AT02724175T patent/ATE416157T1/de not_active IP Right Cessation
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Also Published As
| Publication number | Publication date |
|---|---|
| EP1377540B1 (de) | 2008-12-03 |
| DE60230127D1 (de) | 2009-01-15 |
| EP1377540A1 (de) | 2004-01-07 |
| DE10112771A1 (de) | 2002-09-26 |
| ATE416157T1 (de) | 2008-12-15 |
| JP2004525925A (ja) | 2004-08-26 |
| AU2002254900B2 (en) | 2008-04-10 |
| MXPA03008215A (es) | 2004-01-29 |
| ES2316556T3 (es) | 2009-04-16 |
| US20040092454A1 (en) | 2004-05-13 |
| US7632951B2 (en) | 2009-12-15 |
| HUP0303514A2 (hu) | 2004-01-28 |
| JP4327461B2 (ja) | 2009-09-09 |
| CN1582271A (zh) | 2005-02-16 |
| WO2002074730A1 (en) | 2002-09-26 |
| CA2440644C (en) | 2011-10-18 |
| CA2440644A1 (en) | 2002-09-26 |
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