CN104470521B - 脑啡肽酶抑制剂 - Google Patents
脑啡肽酶抑制剂 Download PDFInfo
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- CN104470521B CN104470521B CN201380030078.1A CN201380030078A CN104470521B CN 104470521 B CN104470521 B CN 104470521B CN 201380030078 A CN201380030078 A CN 201380030078A CN 104470521 B CN104470521 B CN 104470521B
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- 0 CC(c1n[n](*)c(C)c1)=O Chemical compound CC(c1n[n](*)c(C)c1)=O 0.000 description 13
- CBYNNHHZLRNYCL-XQRVVYSFSA-N C/C(/O)=C(\CCl)/OC(C)=O Chemical compound C/C(/O)=C(\CCl)/OC(C)=O CBYNNHHZLRNYCL-XQRVVYSFSA-N 0.000 description 1
- ISULZYQDGYXDFW-UHFFFAOYSA-N CC(C)CC(Cl)=O Chemical compound CC(C)CC(Cl)=O ISULZYQDGYXDFW-UHFFFAOYSA-N 0.000 description 1
- GTPIYXOPQHCHQW-XMMPIXPASA-N CC(C)CC(O[C@H](CN(Cc(cc1)ccc1-c(cc(cc1)Cl)c1F)NC(c1cc(C(C)=O)n[nH]1)=O)C(O)=O)=O Chemical compound CC(C)CC(O[C@H](CN(Cc(cc1)ccc1-c(cc(cc1)Cl)c1F)NC(c1cc(C(C)=O)n[nH]1)=O)C(O)=O)=O GTPIYXOPQHCHQW-XMMPIXPASA-N 0.000 description 1
- CEFVHPDFGLDQKU-YFKPBYRVSA-N CC(C)[C@@H](C(O)=O)NC(OC)=O Chemical compound CC(C)[C@@H](C(O)=O)NC(OC)=O CEFVHPDFGLDQKU-YFKPBYRVSA-N 0.000 description 1
- NHUFQUUQDKNIOP-QMMMGPOBSA-N CC(C)[C@@H](C(OCCl)=O)NC(OC(C)(C)C)=O Chemical compound CC(C)[C@@H](C(OCCl)=O)NC(OC(C)(C)C)=O NHUFQUUQDKNIOP-QMMMGPOBSA-N 0.000 description 1
- FJLLDDPSWDIRDT-LPVMQEMWSA-N CC(C)[C@@H](C(OC[n](c(C(NN(C[C@@H](C)C(O)=O)Cc(cc1)ccc1/C(/C(/CF)=C\C#C)=C/CCl)=O)c1)nc1C(C)=O)=O)N Chemical compound CC(C)[C@@H](C(OC[n](c(C(NN(C[C@@H](C)C(O)=O)Cc(cc1)ccc1/C(/C(/CF)=C\C#C)=C/CCl)=O)c1)nc1C(C)=O)=O)N FJLLDDPSWDIRDT-LPVMQEMWSA-N 0.000 description 1
- HOAOHXCMFIYALX-UHFFFAOYSA-N CC(NC1=O)=NN1c1cccc(Cl)c1 Chemical compound CC(NC1=O)=NN1c1cccc(Cl)c1 HOAOHXCMFIYALX-UHFFFAOYSA-N 0.000 description 1
- UJNDKPSRAVPCOL-OAQYLSRUSA-N CC(O1)=C(CO[n]2nnc(CC(NN(C[C@H](C(O)=O)O)Cc(cc3)ccc3-c(cc(cc3)Cl)c3Cl)=O)c2)OC1=O Chemical compound CC(O1)=C(CO[n]2nnc(CC(NN(C[C@H](C(O)=O)O)Cc(cc3)ccc3-c(cc(cc3)Cl)c3Cl)=O)c2)OC1=O UJNDKPSRAVPCOL-OAQYLSRUSA-N 0.000 description 1
- ITQMVIBDWFMDGP-RUZDIDTESA-N CC(OCOC([C@@H](CCN(Cc(cc1)ccc1-c(cc(cc1)Cl)c1F)NC(c(nc1O)n[n]1-c1cccc(Cl)c1)=O)O)=O)=O Chemical compound CC(OCOC([C@@H](CCN(Cc(cc1)ccc1-c(cc(cc1)Cl)c1F)NC(c(nc1O)n[n]1-c1cccc(Cl)c1)=O)O)=O)=O ITQMVIBDWFMDGP-RUZDIDTESA-N 0.000 description 1
- YVDLGTJEGVMCLG-XMMPIXPASA-N CC(OCOc1nc(C(NN(C[C@H](C(O)=O)O)Cc(cc2)ccc2-c(cc(cc2)Cl)c2F)=O)n[n]1-c1cccc(Cl)c1)=O Chemical compound CC(OCOc1nc(C(NN(C[C@H](C(O)=O)O)Cc(cc2)ccc2-c(cc(cc2)Cl)c2F)=O)n[n]1-c1cccc(Cl)c1)=O YVDLGTJEGVMCLG-XMMPIXPASA-N 0.000 description 1
- QAHJCGZSUSCIQV-UHFFFAOYSA-N CC(c1n[nH]c(C(NN(CCCCC(O)=O)Cc(cc2)ccc2-c(cc(cc2)Cl)c2F)=O)c1)=O Chemical compound CC(c1n[nH]c(C(NN(CCCCC(O)=O)Cc(cc2)ccc2-c(cc(cc2)Cl)c2F)=O)c1)=O QAHJCGZSUSCIQV-UHFFFAOYSA-N 0.000 description 1
- NTZBHPNBUVRNEW-UHFFFAOYSA-N CCC(O1)=C(NC[IH]C)OC1=O Chemical compound CCC(O1)=C(NC[IH]C)OC1=O NTZBHPNBUVRNEW-UHFFFAOYSA-N 0.000 description 1
- BDPZFQLKFUONAG-UHFFFAOYSA-N CCCC(OCCl)=O Chemical compound CCCC(OCCl)=O BDPZFQLKFUONAG-UHFFFAOYSA-N 0.000 description 1
- VCXMSJXIUVXKKG-QGZVFWFLSA-N CCOC([C@@H](CN(Cc(cc1)ccc1-c(cc(cc1)Cl)c1F)N)O)=O Chemical compound CCOC([C@@H](CN(Cc(cc1)ccc1-c(cc(cc1)Cl)c1F)N)O)=O VCXMSJXIUVXKKG-QGZVFWFLSA-N 0.000 description 1
- COHHOTGVGWYDIS-UHFFFAOYSA-N CNNCc(cc1)ccc1Br Chemical compound CNNCc(cc1)ccc1Br COHHOTGVGWYDIS-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N O=Cc(cc1)ccc1Br Chemical compound O=Cc(cc1)ccc1Br ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- DYVXLFGZOUVHLL-HSZRJFAPSA-N O[C@H](CN(Cc(cc1)ccc1-c(cc(cc1)Cl)c1F)NC(c1cc(-c2ccccc2F)n[o]1)=O)C(O)=O Chemical compound O[C@H](CN(Cc(cc1)ccc1-c(cc(cc1)Cl)c1F)NC(c1cc(-c2ccccc2F)n[o]1)=O)C(O)=O DYVXLFGZOUVHLL-HSZRJFAPSA-N 0.000 description 1
- OGJIKQZDJPWHKV-HSZRJFAPSA-N O[C@H](CN(Cc(cc1)ccc1-c1cc(Cl)ccc1)NC(c1cc(O)n[o]1)=O)C(OCC(c1ccccc1)=O)=O Chemical compound O[C@H](CN(Cc(cc1)ccc1-c1cc(Cl)ccc1)NC(c1cc(O)n[o]1)=O)C(OCC(c1ccccc1)=O)=O OGJIKQZDJPWHKV-HSZRJFAPSA-N 0.000 description 1
Classifications
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- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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- C07F9/02—Phosphorus compounds
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- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
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- C—CHEMISTRY; METALLURGY
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- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
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- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members 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
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- Chemical & Material Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261657220P | 2012-06-08 | 2012-06-08 | |
| US61/657,220 | 2012-06-08 | ||
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| JP2012526810A (ja) | 2009-05-13 | 2012-11-01 | イントラ−セルラー・セラピーズ・インコーポレイテッド | 有機化合物 |
| KR101892611B1 (ko) | 2010-12-15 | 2018-08-28 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | 네프릴리신 억제제 |
| CN105061314A (zh) | 2010-12-15 | 2015-11-18 | 施万生物制药研发Ip有限责任公司 | 脑啡肽酶抑制剂 |
| EP2675792B1 (en) | 2011-02-17 | 2016-01-06 | Theravance Biopharma R&D IP, LLC | Substituted aminobutyric derivatives as neprilysin inhibitors |
| KR101854874B1 (ko) | 2011-02-17 | 2018-05-04 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | 네프릴리신 억제제로서 치환된 아미노부티릭 유도체 |
| CA2835216A1 (en) | 2011-05-31 | 2012-12-06 | Theravance, Inc. | Neprilysin inhibitors |
| TWI560172B (en) | 2011-11-02 | 2016-12-01 | Theravance Biopharma R&D Ip Llc | Neprilysin inhibitors |
| US8871792B2 (en) | 2012-06-08 | 2014-10-28 | Theravance Biopharma R&D Ip, Llc | Neprilysin inhibitors |
| ES2615275T3 (es) | 2012-08-08 | 2017-06-06 | Theravance Biopharma R&D Ip, Llc | Inhibidores de neprilisina |
| WO2014127331A1 (en) | 2013-02-17 | 2014-08-21 | Intra-Cellular Therapies, Inc. | Novel uses |
| CA2902456A1 (en) | 2013-03-05 | 2014-09-12 | Theravance Biopharma R&D Ip, Llc | Neprilysin inhibitors |
| US9585882B2 (en) | 2014-01-30 | 2017-03-07 | Theravance Biopharma R&D Ip, Llc | Neprilysin inhibitors |
| MX2016009760A (es) | 2014-01-30 | 2016-11-08 | Theravance Biopharma R&D Ip Llc | Inhibidores de neprilisina. |
| JP6591530B2 (ja) | 2014-08-07 | 2019-10-16 | イントラ−セルラー・セラピーズ・インコーポレイテッドIntra−Cellular Therapies, Inc. | 有機化合物 |
| CN107257785B (zh) | 2015-02-11 | 2020-07-07 | 施万生物制药研发Ip有限责任公司 | 作为脑啡肽酶抑制剂的(2s,4r)-5-(5’-氯-2’-氟联苯-4-基)-4-(乙氧基草酰基氨基)-2-羟甲基-2-甲基戊酸 |
| DK3259255T3 (da) | 2015-02-19 | 2021-01-18 | Theravance Biopharma R&D Ip Llc | (2r,4r)-5-(5'-chlor-2'-fluorbiphenyl-4-yl)-2-hydroxy-4-[(5-methyloxazol-2-carbonyl)amino]pentansyre |
| CN106543139B (zh) * | 2015-09-17 | 2020-03-17 | 沈阳中化农药化工研发有限公司 | 一种三唑酮类化合物及其用途 |
| ES2880123T3 (es) | 2016-03-08 | 2021-11-23 | Theravance Biopharma R&D Ip Llc | Acido (25,4R)-5-(5'-cloro-2'-fluoro-[1,1'-bifenil]-4-il)-2-(etoximetil)-4-(3-hidroxilisoxazol-5-carboxamido)-2-metilpentanoico cristalino y usos del mismo |
| JP2019510039A (ja) | 2016-03-28 | 2019-04-11 | イントラ−セルラー・セラピーズ・インコーポレイテッドIntra−Cellular Therapies, Inc. | 新規組成物および方法 |
| US11839614B2 (en) | 2018-01-31 | 2023-12-12 | Intra-Cellular Therapies, Inc. | Methods for treating or mitigating cardiotoxicity characterized by inhibition of adenosine A2 signaling and/or adenosine A2 receptor expression |
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| CN102448928A (zh) * | 2009-05-28 | 2012-05-09 | 诺瓦提斯公司 | 作为中性溶酶(neprilysin)抑制剂的取代的氨基丁酸衍生物 |
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