BR112014016204B1 - Derivado de sitaxentana - Google Patents
Derivado de sitaxentana Download PDFInfo
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- BR112014016204B1 BR112014016204B1 BR112014016204-2A BR112014016204A BR112014016204B1 BR 112014016204 B1 BR112014016204 B1 BR 112014016204B1 BR 112014016204 A BR112014016204 A BR 112014016204A BR 112014016204 B1 BR112014016204 B1 BR 112014016204B1
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- PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical class CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 title abstract description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 140
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims description 4
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 4
- UHOCAYVFENBVCB-UHFFFAOYSA-N n-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-[2-(6-methyl-1,3-dihydro-2-benzofuran-5-yl)acetyl]thiophene-3-sulfonamide Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3COCC=3C=2)C)=C1Cl UHOCAYVFENBVCB-UHFFFAOYSA-N 0.000 claims description 3
- 230000003449 preventive effect Effects 0.000 claims description 3
- 229960002578 sitaxentan Drugs 0.000 abstract description 23
- 230000002401 inhibitory effect Effects 0.000 abstract description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 12
- 125000005843 halogen group Chemical group 0.000 abstract description 9
- 125000000217 alkyl group Chemical group 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- -1 4-chloro-3-methyl-1,2-oxazol-5-yl Chemical group 0.000 description 39
- 239000002904 solvent Substances 0.000 description 38
- 238000000034 method Methods 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 29
- 239000000203 mixture Substances 0.000 description 28
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 27
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 238000004519 manufacturing process Methods 0.000 description 21
- 239000000243 solution Substances 0.000 description 19
- 239000007858 starting material Substances 0.000 description 19
- 238000012360 testing method Methods 0.000 description 19
- 239000000126 substance Substances 0.000 description 18
- 239000000758 substrate Substances 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- 230000008569 process Effects 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- 101000967336 Homo sapiens Endothelin-1 receptor Proteins 0.000 description 10
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- 238000010898 silica gel chromatography Methods 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
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- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
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- YUIOPHXTILULQC-UHFFFAOYSA-N 1,4-Dithiane-2,5-diol Chemical compound OC1CSC(O)CS1 YUIOPHXTILULQC-UHFFFAOYSA-N 0.000 description 6
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- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
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- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical group C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 4
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 4
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- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
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- 125000001309 chloro group Chemical group Cl* 0.000 description 4
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- OGGHNQUXFGVBEK-UHFFFAOYSA-N (6-methyl-1,3-dihydro-2-benzofuran-5-yl)methanol Chemical compound C1=C(CO)C(C)=CC2=C1COC2 OGGHNQUXFGVBEK-UHFFFAOYSA-N 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 2
- VRGYYWMUTXDXKN-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]-n-methoxy-n-methylthiophene-2-carboxamide Chemical compound S1C=CC(S(=O)(=O)NC2=C(C(C)=NO2)Cl)=C1C(=O)N(C)OC VRGYYWMUTXDXKN-UHFFFAOYSA-N 0.000 description 2
- BFHXYQAPYRDEDW-UHFFFAOYSA-N 3-[(4-chloro-3-methyl-1,2-oxazol-5-yl)sulfamoyl]thiophene-2-carboxylic acid Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(O)=O)=C1Cl BFHXYQAPYRDEDW-UHFFFAOYSA-N 0.000 description 2
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
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| PCT/JP2013/051857 WO2013115162A1 (ja) | 2012-01-31 | 2013-01-29 | シタキセンタン誘導体 |
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| BR112014016204A8 BR112014016204A8 (pt) | 2017-07-04 |
| BR112014016204B1 true BR112014016204B1 (pt) | 2020-09-24 |
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| TW (1) | TW201336496A (enExample) |
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| US20240287053A1 (en) * | 2021-06-22 | 2024-08-29 | Alchemedicine, Inc. | Compound, endothelin-a receptor antagonist, and pharmaceutical composition |
| JP2025183466A (ja) * | 2022-11-11 | 2025-12-17 | 株式会社アークメディスン | 化合物、エンドセリンａ受容体拮抗剤、アンジオテンシンｉｉタイプ１受容体拮抗剤及び医薬組成物 |
| WO2024242594A1 (ru) * | 2023-05-23 | 2024-11-28 | Общество С Ограниченной Ответственностью "Ифар" | Средство для лечения легочных гипертензий |
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| US4861366A (en) | 1984-08-27 | 1989-08-29 | E. I. Du Pont De Nemours And Company | Herbicidal acetals and ketals |
| US4659369A (en) | 1984-08-27 | 1987-04-21 | E. I. Du Pont De Nemours And Company | Herbicidal acetals and ketals |
| US4753672A (en) | 1985-07-16 | 1988-06-28 | E. I. Du Pont De Nemours And Company | Herbicidal acetals and ketals |
| TW224462B (enExample) * | 1992-02-24 | 1994-06-01 | Squibb & Sons Inc | |
| NZ306734A (enExample) * | 1995-04-04 | 2000-01-28 | Texas Biotechnology Corp | |
| EE200200363A (et) * | 1999-12-31 | 2003-08-15 | Texas Biotechnology Corporation | Sulfoonamiidid ja nende derivaadid, mis moduleerivad endoteliini aktiivsust |
| US20060205733A1 (en) * | 2004-08-26 | 2006-09-14 | Encysive Pharmaceuticals | Endothelin a receptor antagonists in combination with phosphodiesterase 5 inhibitors and uses thereof |
| JP2009184924A (ja) | 2006-05-31 | 2009-08-20 | Eisai R & D Management Co Ltd | 生物学的試薬用化合物 |
| CN101730694A (zh) * | 2007-04-10 | 2010-06-09 | 奥斯拜客斯制药有限公司 | 用于治疗高血压的取代的氘富集的噻吩 |
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2013
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- 2013-01-29 AU AU2013216122A patent/AU2013216122B9/en not_active Ceased
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- 2013-01-29 US US13/752,660 patent/US8592470B2/en active Active
- 2013-01-29 TW TW102103329A patent/TW201336496A/zh unknown
- 2013-01-29 CA CA2861477A patent/CA2861477C/en active Active
- 2013-01-29 WO PCT/JP2013/051857 patent/WO2013115162A1/ja not_active Ceased
- 2013-01-29 IN IN4945CHN2014 patent/IN2014CN04945A/en unknown
- 2013-01-29 ES ES13743422.1T patent/ES2651293T3/es active Active
- 2013-01-29 KR KR1020147021115A patent/KR101933251B1/ko active Active
- 2013-01-29 BR BR112014016204-2A patent/BR112014016204B1/pt not_active IP Right Cessation
- 2013-01-29 AR ARP130100263A patent/AR089838A1/es unknown
- 2013-01-29 RU RU2014126427A patent/RU2622386C2/ru active
- 2013-01-29 MX MX2014007619A patent/MX358151B/es active IP Right Grant
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2014
- 2014-06-16 IL IL233171A patent/IL233171A/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013115162A1 (ja) | 2013-08-08 |
| US20130197045A1 (en) | 2013-08-01 |
| MX2014007619A (es) | 2014-09-15 |
| IN2014CN04945A (enExample) | 2015-09-18 |
| AU2013216122B2 (en) | 2016-12-08 |
| CA2861477A1 (en) | 2013-08-08 |
| BR112014016204A2 (pt) | 2017-06-13 |
| CN104039781A (zh) | 2014-09-10 |
| KR20140117455A (ko) | 2014-10-07 |
| MX358151B (es) | 2018-08-07 |
| US8592470B2 (en) | 2013-11-26 |
| RU2622386C2 (ru) | 2017-06-15 |
| TW201336496A (zh) | 2013-09-16 |
| JPWO2013115162A1 (ja) | 2015-05-11 |
| CN104039781B (zh) | 2016-08-17 |
| BR112014016204A8 (pt) | 2017-07-04 |
| RU2014126427A (ru) | 2016-03-20 |
| CA2861477C (en) | 2018-01-02 |
| AR089838A1 (es) | 2014-09-17 |
| IL233171A (en) | 2017-07-31 |
| AU2013216122A1 (en) | 2014-07-24 |
| EP2810943A4 (en) | 2015-09-02 |
| ES2651293T3 (es) | 2018-01-25 |
| EP2810943B1 (en) | 2017-09-27 |
| EP2810943A1 (en) | 2014-12-10 |
| KR101933251B1 (ko) | 2018-12-27 |
| IL233171A0 (en) | 2014-07-31 |
| AU2013216122B9 (en) | 2017-02-02 |
| JP6144631B2 (ja) | 2017-06-07 |
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