TW555749B - Novel carboxylic acid derivatives with 4,5-substituted pyrimidine ring, their preparation and pharmaceutical preparation comprising the same - Google Patents
Novel carboxylic acid derivatives with 4,5-substituted pyrimidine ring, their preparation and pharmaceutical preparation comprising the same Download PDFInfo
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- TW555749B TW555749B TW089113992A TW89113992A TW555749B TW 555749 B TW555749 B TW 555749B TW 089113992 A TW089113992 A TW 089113992A TW 89113992 A TW89113992 A TW 89113992A TW 555749 B TW555749 B TW 555749B
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- Prior art keywords
- phenyl
- cooh
- alkyl
- ome
- group
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- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title description 8
- 125000000714 pyrimidinyl group Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 47
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 30
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 239000001301 oxygen Substances 0.000 claims abstract description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical class 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 23
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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 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
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- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 abstract description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- -1 6-substituted pyrimidine rings Chemical group 0.000 description 92
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 57
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 125000005843 halogen group Chemical group 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
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- 239000002904 solvent Substances 0.000 description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
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- 239000011593 sulfur Substances 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
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- 125000004001 thioalkyl group Chemical group 0.000 description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
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- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
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- 102100033902 Endothelin-1 Human genes 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
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- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
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- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 3
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- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
- A61P5/16—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4 for decreasing, blocking or antagonising the activity of the thyroid hormones
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19933164A DE19933164A1 (de) | 1999-07-20 | 1999-07-20 | Neue Carbonsäurederivate mit 5,6 substituiertem Pyrimidinring, ihre Herstellung und Verwendung als Endothelin Rezeptorantagonisten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW555749B true TW555749B (en) | 2003-10-01 |
Family
ID=7914884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW089113992A TW555749B (en) | 1999-07-20 | 2000-07-13 | Novel carboxylic acid derivatives with 4,5-substituted pyrimidine ring, their preparation and pharmaceutical preparation comprising the same |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP1196394A1 (cs) |
| JP (1) | JP2003505377A (cs) |
| KR (1) | KR20020019550A (cs) |
| CN (1) | CN1367778A (cs) |
| AR (1) | AR030026A1 (cs) |
| AU (1) | AU6561500A (cs) |
| BG (1) | BG106321A (cs) |
| BR (1) | BR0012592A (cs) |
| CA (1) | CA2379545A1 (cs) |
| CZ (1) | CZ2002190A3 (cs) |
| DE (1) | DE19933164A1 (cs) |
| HU (1) | HUP0202646A3 (cs) |
| IL (1) | IL147666A0 (cs) |
| MX (1) | MXPA02000616A (cs) |
| NO (1) | NO20020254L (cs) |
| PL (1) | PL353165A1 (cs) |
| SK (1) | SK772002A3 (cs) |
| TR (1) | TR200200622T2 (cs) |
| TW (1) | TW555749B (cs) |
| WO (1) | WO2001005771A1 (cs) |
| ZA (1) | ZA200200333B (cs) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8962832B2 (en) * | 2009-07-10 | 2015-02-24 | Cadila Healthcare Limited | Process for the preparation of ambrisentan and novel intermediates thereof |
| WO2011114338A1 (en) | 2010-03-15 | 2011-09-22 | Natco Pharma Limited | A process for the preparation of highly pure ambrisentan |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19636046A1 (de) * | 1996-09-05 | 1998-03-12 | Basf Ag | Neue Carbonsäurederivate, ihre Herstellung und Verwendung als gemischte ET¶A¶/ET¶B¶-Rezeptorantagonisten |
| CN1278251A (zh) * | 1997-10-31 | 2000-12-27 | Basf公司 | 新的带酰胺侧链的羧酸衍生物及其制备方法和作为内皮素受体拮抗剂的用途 |
-
1999
- 1999-07-20 DE DE19933164A patent/DE19933164A1/de not_active Withdrawn
-
2000
- 2000-07-05 PL PL00353165A patent/PL353165A1/xx not_active Application Discontinuation
- 2000-07-05 EP EP00953009A patent/EP1196394A1/de not_active Withdrawn
- 2000-07-05 CZ CZ2002190A patent/CZ2002190A3/cs unknown
- 2000-07-05 CN CN00810533A patent/CN1367778A/zh active Pending
- 2000-07-05 IL IL14766600A patent/IL147666A0/xx unknown
- 2000-07-05 CA CA002379545A patent/CA2379545A1/en not_active Abandoned
- 2000-07-05 BR BR0012592-0A patent/BR0012592A/pt not_active IP Right Cessation
- 2000-07-05 AU AU65615/00A patent/AU6561500A/en not_active Abandoned
- 2000-07-05 KR KR1020027000815A patent/KR20020019550A/ko not_active Ceased
- 2000-07-05 WO PCT/EP2000/006293 patent/WO2001005771A1/de not_active Application Discontinuation
- 2000-07-05 MX MXPA02000616A patent/MXPA02000616A/es unknown
- 2000-07-05 HU HU0202646A patent/HUP0202646A3/hu unknown
- 2000-07-05 JP JP2001511432A patent/JP2003505377A/ja not_active Abandoned
- 2000-07-05 TR TR2002/00622T patent/TR200200622T2/xx unknown
- 2000-07-05 SK SK77-2002A patent/SK772002A3/sk unknown
- 2000-07-13 TW TW089113992A patent/TW555749B/zh active
- 2000-07-17 AR ARP000103661A patent/AR030026A1/es unknown
-
2002
- 2002-01-15 ZA ZA200200333A patent/ZA200200333B/en unknown
- 2002-01-17 NO NO20020254A patent/NO20020254L/no not_active Application Discontinuation
- 2002-01-18 BG BG106321A patent/BG106321A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL147666A0 (en) | 2002-08-14 |
| CZ2002190A3 (cs) | 2003-08-13 |
| TR200200622T2 (cs) | 2002-06-21 |
| EP1196394A1 (de) | 2002-04-17 |
| CA2379545A1 (en) | 2001-01-25 |
| AR030026A1 (es) | 2003-08-13 |
| DE19933164A1 (de) | 2001-01-25 |
| HUP0202646A2 (hu) | 2003-02-28 |
| PL353165A1 (en) | 2003-10-20 |
| NO20020254D0 (no) | 2002-01-17 |
| CN1367778A (zh) | 2002-09-04 |
| AU6561500A (en) | 2001-02-05 |
| HUP0202646A3 (en) | 2003-03-28 |
| BG106321A (en) | 2002-08-30 |
| MXPA02000616A (es) | 2002-08-30 |
| BR0012592A (pt) | 2002-05-28 |
| ZA200200333B (en) | 2003-04-30 |
| NO20020254L (no) | 2002-02-20 |
| SK772002A3 (en) | 2003-01-09 |
| KR20020019550A (ko) | 2002-03-12 |
| WO2001005771A1 (de) | 2001-01-25 |
| JP2003505377A (ja) | 2003-02-12 |
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