ZA200200333B - Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists. - Google Patents
Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists. Download PDFInfo
- Publication number
- ZA200200333B ZA200200333B ZA200200333A ZA200200333A ZA200200333B ZA 200200333 B ZA200200333 B ZA 200200333B ZA 200200333 A ZA200200333 A ZA 200200333A ZA 200200333 A ZA200200333 A ZA 200200333A ZA 200200333 B ZA200200333 B ZA 200200333B
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- ZA
- South Africa
- Prior art keywords
- alkyl
- alkoxy
- alkylthio
- phenyl
- compounds
- Prior art date
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- 229940118365 Endothelin receptor antagonist Drugs 0.000 title claims description 11
- 239000002308 endothelin receptor antagonist Substances 0.000 title claims description 11
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 title 1
- -1 mercapto, amino Chemical group 0.000 claims description 61
- 150000001875 compounds Chemical class 0.000 claims description 52
- 150000003254 radicals Chemical class 0.000 claims description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 108050009340 Endothelin Proteins 0.000 claims description 20
- 102000002045 Endothelin Human genes 0.000 claims description 20
- 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 20
- 239000000203 mixture Substances 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
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- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 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 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims description 5
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- 150000001340 alkali metals Chemical class 0.000 claims description 5
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- 229940079593 drug Drugs 0.000 claims description 5
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
- 206010033645 Pancreatitis Diseases 0.000 claims description 4
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 4
- 125000004450 alkenylene group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 4
- 150000005840 aryl radicals Chemical class 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 3
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
- 201000006474 Brain Ischemia Diseases 0.000 claims description 3
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- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 3
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- 201000011040 acute kidney failure Diseases 0.000 claims description 3
- 201000003229 acute pancreatitis Diseases 0.000 claims description 3
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- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
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- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 230000036454 renin-angiotensin system Effects 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
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- 239000002934 diuretic Substances 0.000 claims description 2
- 229940030606 diuretics Drugs 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 239000002461 renin inhibitor Substances 0.000 claims description 2
- 229940086526 renin-inhibitors Drugs 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 6
- 201000010099 disease Diseases 0.000 claims 5
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- 108090000028 Neprilysin Proteins 0.000 claims 2
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 229940123413 Angiotensin II antagonist Drugs 0.000 claims 1
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 1
- 239000000480 calcium channel blocker Substances 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 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
- 239000000243 solution Substances 0.000 description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
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- FXTPUVLWVRTMHV-UHFFFAOYSA-N 2-(4-methoxy-5-methylpyrimidin-2-yl)oxy-3,3-diphenyl-3-phenylmethoxypropanoic acid Chemical compound C1=C(C)C(OC)=NC(OC(C(O)=O)C(OCC=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 FXTPUVLWVRTMHV-UHFFFAOYSA-N 0.000 description 3
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- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 206010038464 renal hypertension Diseases 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
- 238000005690 transetherification reaction Methods 0.000 description 1
- CMMXCVYESRODNH-UHFFFAOYSA-N trichloroepoxyethane Chemical class ClC1OC1(Cl)Cl CMMXCVYESRODNH-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000002525 vasculotropin inhibitor Substances 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (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 |
|---|---|
| ZA200200333B true ZA200200333B (en) | 2003-04-30 |
Family
ID=7914884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200200333A ZA200200333B (en) | 1999-07-20 | 2002-01-15 | Novel carboxylic acid derivatives with 5,6 substituted pyrimidine ring, the production and utilization thereof as endothelin receptor antagonists. |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP1196394A1 (hu) |
| JP (1) | JP2003505377A (hu) |
| KR (1) | KR20020019550A (hu) |
| CN (1) | CN1367778A (hu) |
| AR (1) | AR030026A1 (hu) |
| AU (1) | AU6561500A (hu) |
| BG (1) | BG106321A (hu) |
| BR (1) | BR0012592A (hu) |
| CA (1) | CA2379545A1 (hu) |
| CZ (1) | CZ2002190A3 (hu) |
| DE (1) | DE19933164A1 (hu) |
| HU (1) | HUP0202646A3 (hu) |
| IL (1) | IL147666A0 (hu) |
| MX (1) | MXPA02000616A (hu) |
| NO (1) | NO20020254L (hu) |
| PL (1) | PL353165A1 (hu) |
| SK (1) | SK772002A3 (hu) |
| TR (1) | TR200200622T2 (hu) |
| TW (1) | TW555749B (hu) |
| WO (1) | WO2001005771A1 (hu) |
| ZA (1) | ZA200200333B (hu) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011004402A2 (en) * | 2009-07-10 | 2011-01-13 | Cadila Healthcare Limited | Improved process for the preparation of ambrisentan and novel intermediates thereof |
| US20130060031A1 (en) | 2010-03-15 | 2013-03-07 | Natco Pharma Limited | 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 |
| WO1999023078A2 (de) * | 1997-10-31 | 1999-05-14 | Basf Aktiengesellschaft | Neue carbonsäurederivate, die amidseitenketten tragen, ihre herstellung und verwendung als endothelin-rezeptorantagonisten |
-
1999
- 1999-07-20 DE DE19933164A patent/DE19933164A1/de not_active Withdrawn
-
2000
- 2000-07-05 CN CN00810533A patent/CN1367778A/zh active Pending
- 2000-07-05 JP JP2001511432A patent/JP2003505377A/ja not_active Abandoned
- 2000-07-05 IL IL14766600A patent/IL147666A0/xx unknown
- 2000-07-05 AU AU65615/00A patent/AU6561500A/en not_active Abandoned
- 2000-07-05 KR KR1020027000815A patent/KR20020019550A/ko not_active Application Discontinuation
- 2000-07-05 HU HU0202646A patent/HUP0202646A3/hu unknown
- 2000-07-05 WO PCT/EP2000/006293 patent/WO2001005771A1/de not_active Application Discontinuation
- 2000-07-05 SK SK77-2002A patent/SK772002A3/sk unknown
- 2000-07-05 MX MXPA02000616A patent/MXPA02000616A/es unknown
- 2000-07-05 PL PL00353165A patent/PL353165A1/xx not_active Application Discontinuation
- 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 TR TR2002/00622T patent/TR200200622T2/xx unknown
- 2000-07-05 EP EP00953009A patent/EP1196394A1/de not_active Withdrawn
- 2000-07-05 CZ CZ2002190A patent/CZ2002190A3/cs 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 |
|---|---|
| HUP0202646A3 (en) | 2003-03-28 |
| CZ2002190A3 (cs) | 2003-08-13 |
| SK772002A3 (en) | 2003-01-09 |
| CN1367778A (zh) | 2002-09-04 |
| NO20020254L (no) | 2002-02-20 |
| BG106321A (en) | 2002-08-30 |
| WO2001005771A1 (de) | 2001-01-25 |
| TW555749B (en) | 2003-10-01 |
| TR200200622T2 (hu) | 2002-06-21 |
| AR030026A1 (es) | 2003-08-13 |
| HUP0202646A2 (hu) | 2003-02-28 |
| AU6561500A (en) | 2001-02-05 |
| MXPA02000616A (es) | 2002-08-30 |
| JP2003505377A (ja) | 2003-02-12 |
| PL353165A1 (en) | 2003-10-20 |
| DE19933164A1 (de) | 2001-01-25 |
| EP1196394A1 (de) | 2002-04-17 |
| BR0012592A (pt) | 2002-05-28 |
| CA2379545A1 (en) | 2001-01-25 |
| IL147666A0 (en) | 2002-08-14 |
| KR20020019550A (ko) | 2002-03-12 |
| NO20020254D0 (no) | 2002-01-17 |
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