CN101570510A - 喹啉类化合物及其药物组合物、制备方法和应用 - Google Patents
喹啉类化合物及其药物组合物、制备方法和应用 Download PDFInfo
- Publication number
- CN101570510A CN101570510A CNA2008100369307A CN200810036930A CN101570510A CN 101570510 A CN101570510 A CN 101570510A CN A2008100369307 A CNA2008100369307 A CN A2008100369307A CN 200810036930 A CN200810036930 A CN 200810036930A CN 101570510 A CN101570510 A CN 101570510A
- Authority
- CN
- China
- Prior art keywords
- quinoline
- dihydroxyl
- fluoro
- general formula
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 Quinoline compound Chemical class 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 14
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title abstract description 6
- 239000012453 solvate Substances 0.000 claims abstract description 20
- 230000003287 optical effect Effects 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- 150000002367 halogens Chemical class 0.000 claims abstract description 12
- 201000010099 disease Diseases 0.000 claims abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 5
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 51
- 159000000007 calcium salts Chemical class 0.000 claims description 49
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 48
- YURNCBVQZBJDAJ-AATRIKPKSA-N (E)-hept-2-enoic acid Chemical compound CCCC\C=C\C(O)=O YURNCBVQZBJDAJ-AATRIKPKSA-N 0.000 claims description 45
- 150000001875 compounds Chemical class 0.000 claims description 38
- 239000011575 calcium Substances 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 32
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 27
- 239000003513 alkali Substances 0.000 claims description 24
- 239000003960 organic solvent Substances 0.000 claims description 23
- 229940111121 antirheumatic drug quinolines Drugs 0.000 claims description 20
- 150000003248 quinolines Chemical class 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 239000011734 sodium Substances 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 229910021529 ammonia Inorganic materials 0.000 claims description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 230000001476 alcoholic effect Effects 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- RWGFKTVRMDUZSP-UHFFFAOYSA-N isopropyl-benzene Natural products CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 claims description 10
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 9
- 239000000920 calcium hydroxide Substances 0.000 claims description 9
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 9
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 9
- RDOXTESZEPMUJZ-UHFFFAOYSA-N methyl phenyl ether Natural products COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 7
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical group [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 6
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 6
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 6
- 239000001110 calcium chloride Substances 0.000 claims description 6
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 claims description 5
- XAADEOMJJKSZKX-IPZCTEOASA-M [Na+].C(\C=C\CCCC)(=O)[O-] Chemical compound [Na+].C(\C=C\CCCC)(=O)[O-] XAADEOMJJKSZKX-IPZCTEOASA-M 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- KIPFGTAXZBGJCI-IPZCTEOASA-N [NH4+].C(\C=C\CCCC)(=O)[O-] Chemical compound [NH4+].C(\C=C\CCCC)(=O)[O-] KIPFGTAXZBGJCI-IPZCTEOASA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000006606 n-butoxy group Chemical group 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 7
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 abstract description 5
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 abstract description 5
- 230000000055 hyoplipidemic effect Effects 0.000 abstract description 4
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 abstract description 3
- 238000001727 in vivo Methods 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 abstract 1
- 201000005577 familial hyperlipidemia Diseases 0.000 abstract 1
- 230000002349 favourable effect Effects 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 20
- 239000000243 solution Substances 0.000 description 18
- 238000003756 stirring Methods 0.000 description 17
- 229920002554 vinyl polymer Polymers 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 12
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000000967 suction filtration Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 241000286209 Phasianidae Species 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 230000008034 disappearance Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000003810 ethyl acetate extraction Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 150000002596 lactones Chemical group 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 2
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 102000015779 HDL Lipoproteins Human genes 0.000 description 2
- 108010010234 HDL Lipoproteins Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229960005370 atorvastatin Drugs 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 2
- 229960002797 pitavastatin Drugs 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 2
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 229940123934 Reductase inhibitor Drugs 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000004459 forage Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 235000012204 lemonade/lime carbonate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D405/02—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 containing two hetero rings
- C07D405/06—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 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P9/10—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
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/36—Sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
Abstract
Description
Claims (15)
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008100369307A CN101570510B (zh) | 2008-04-30 | 2008-04-30 | 喹啉类化合物及其药物组合物、制备方法和应用 |
EP20090737703 EP2284158A4 (en) | 2008-04-30 | 2009-04-29 | QUINOLINE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, PREPARATION METHODS AND USES THEREOF |
US12/935,212 US8227612B2 (en) | 2008-04-30 | 2009-04-29 | Quinoline compound and pharmaceutical composition, preparation method and uses thereof |
PCT/CN2009/071573 WO2009132593A1 (zh) | 2008-04-30 | 2009-04-29 | 喹啉类化合物及其药物组合物、制备方法和应用 |
JP2010549006A JP5477974B2 (ja) | 2008-04-30 | 2009-04-29 | キノリン類化合物及びその医薬組成物、製造方法並びに使用 |
JP2013165143A JP2014031374A (ja) | 2008-04-30 | 2013-08-08 | キノリン類化合物及びその薬物組成物、製造方法並びに応用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008100369307A CN101570510B (zh) | 2008-04-30 | 2008-04-30 | 喹啉类化合物及其药物组合物、制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101570510A true CN101570510A (zh) | 2009-11-04 |
CN101570510B CN101570510B (zh) | 2011-08-31 |
Family
ID=41230008
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2008100369307A Expired - Fee Related CN101570510B (zh) | 2008-04-30 | 2008-04-30 | 喹啉类化合物及其药物组合物、制备方法和应用 |
Country Status (5)
Country | Link |
---|---|
US (1) | US8227612B2 (zh) |
EP (1) | EP2284158A4 (zh) |
JP (2) | JP5477974B2 (zh) |
CN (1) | CN101570510B (zh) |
WO (1) | WO2009132593A1 (zh) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102276527A (zh) * | 2010-06-08 | 2011-12-14 | 上海医药工业研究院 | 一种喹啉类化合物的制备方法及中间体化合物 |
CN102442997A (zh) * | 2010-10-12 | 2012-05-09 | 上海医药工业研究院 | 一类喹啉衍生物、其制备方法、中间体及其应用 |
CN102477032A (zh) * | 2010-11-26 | 2012-05-30 | 上海医药工业研究院 | 一类2-环丙基-4-取代苯氧基喹啉衍生物、其制备方法、中间体及其应用 |
CN102816203A (zh) * | 2011-06-10 | 2012-12-12 | 上海医药工业研究院 | 一种取代喹啉类化合物及其制备方法、药物组合物和应用 |
CN103381138A (zh) * | 2012-05-03 | 2013-11-06 | 上海现代药物制剂工程研究中心有限公司 | 他汀类药物口服自微乳化释药制剂及其制备方法 |
CN108164517A (zh) * | 2018-02-12 | 2018-06-15 | 李化绪 | (2-甲基环己烷-1-基)亚氨基类化合物及其在高脂血症药物中的应用 |
CN108567743A (zh) * | 2017-03-14 | 2018-09-25 | 上海现代药物制剂工程研究中心有限公司 | 他汀类药物固体分散体、制剂及其制备方法 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101570510B (zh) * | 2008-04-30 | 2011-08-31 | 上海医药工业研究院 | 喹啉类化合物及其药物组合物、制备方法和应用 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3669874D1 (de) * | 1985-08-29 | 1990-05-03 | Hoechst Ag | 3-desmethyl-mevalonsaeurederivate, verfahren zu ihrer herstellung, pharmazeutische praeparate auf basis dieser verbindungen, ihre verwendung sowie zwischenprodukte. |
FR2642065B1 (fr) * | 1989-01-24 | 1991-05-24 | Lipha | Derives d'acides benzocycloalcenyl dihydroxy alcanoiques, procede de preparation et medicaments les contenant |
CA2388182A1 (en) * | 1999-10-27 | 2001-05-03 | Merck & Co., Inc. | Lactonization process |
US7407965B2 (en) * | 2003-04-25 | 2008-08-05 | Gilead Sciences, Inc. | Phosphonate analogs for treating metabolic diseases |
WO2005077916A1 (en) * | 2004-01-19 | 2005-08-25 | Ranbaxy Laboratories Limited | Salts of hmg-coa reductase inhibitors and use thereof |
CN101210011B (zh) | 2006-12-27 | 2010-08-25 | 上海医药工业研究院 | 喹啉类化合物及其中间体、制备方法和应用 |
CN101220021B (zh) | 2007-01-12 | 2010-12-08 | 上海医药工业研究院 | 4-取代苯氧基喹啉类化合物及其中间体、制备方法和应用 |
CN101570510B (zh) * | 2008-04-30 | 2011-08-31 | 上海医药工业研究院 | 喹啉类化合物及其药物组合物、制备方法和应用 |
-
2008
- 2008-04-30 CN CN2008100369307A patent/CN101570510B/zh not_active Expired - Fee Related
-
2009
- 2009-04-29 JP JP2010549006A patent/JP5477974B2/ja not_active Expired - Fee Related
- 2009-04-29 EP EP20090737703 patent/EP2284158A4/en not_active Withdrawn
- 2009-04-29 US US12/935,212 patent/US8227612B2/en not_active Expired - Fee Related
- 2009-04-29 WO PCT/CN2009/071573 patent/WO2009132593A1/zh active Application Filing
-
2013
- 2013-08-08 JP JP2013165143A patent/JP2014031374A/ja active Pending
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102276527A (zh) * | 2010-06-08 | 2011-12-14 | 上海医药工业研究院 | 一种喹啉类化合物的制备方法及中间体化合物 |
CN102276527B (zh) * | 2010-06-08 | 2014-08-13 | 上海医药工业研究院 | 一种喹啉类化合物的制备方法及中间体化合物 |
CN102442997A (zh) * | 2010-10-12 | 2012-05-09 | 上海医药工业研究院 | 一类喹啉衍生物、其制备方法、中间体及其应用 |
CN102477032A (zh) * | 2010-11-26 | 2012-05-30 | 上海医药工业研究院 | 一类2-环丙基-4-取代苯氧基喹啉衍生物、其制备方法、中间体及其应用 |
CN102477032B (zh) * | 2010-11-26 | 2015-04-01 | 上海医药工业研究院 | 一类2-环丙基-4-取代苯氧基喹啉衍生物、其制备方法、中间体及其应用 |
CN102816203A (zh) * | 2011-06-10 | 2012-12-12 | 上海医药工业研究院 | 一种取代喹啉类化合物及其制备方法、药物组合物和应用 |
CN102816203B (zh) * | 2011-06-10 | 2014-09-03 | 上海医药工业研究院 | 一种取代喹啉类化合物及其制备方法、药物组合物和应用 |
CN103381138A (zh) * | 2012-05-03 | 2013-11-06 | 上海现代药物制剂工程研究中心有限公司 | 他汀类药物口服自微乳化释药制剂及其制备方法 |
CN103381138B (zh) * | 2012-05-03 | 2015-09-02 | 上海现代药物制剂工程研究中心有限公司 | 他汀类药物口服自微乳化释药制剂及其制备方法 |
CN108567743A (zh) * | 2017-03-14 | 2018-09-25 | 上海现代药物制剂工程研究中心有限公司 | 他汀类药物固体分散体、制剂及其制备方法 |
CN108164517A (zh) * | 2018-02-12 | 2018-06-15 | 李化绪 | (2-甲基环己烷-1-基)亚氨基类化合物及其在高脂血症药物中的应用 |
Also Published As
Publication number | Publication date |
---|---|
JP2011513341A (ja) | 2011-04-28 |
JP2014031374A (ja) | 2014-02-20 |
EP2284158A4 (en) | 2012-05-09 |
US20110021561A1 (en) | 2011-01-27 |
CN101570510B (zh) | 2011-08-31 |
EP2284158A1 (en) | 2011-02-16 |
US8227612B2 (en) | 2012-07-24 |
WO2009132593A1 (zh) | 2009-11-05 |
JP5477974B2 (ja) | 2014-04-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101570510B (zh) | 喹啉类化合物及其药物组合物、制备方法和应用 | |
TWI481604B (zh) | Novel 5-fluorouracil derivatives | |
JP2008546730A (ja) | 不純物を含まない非晶質ロスバスタチンカルシウムの調製方法 | |
CA2255333C (en) | Quinolinone derivative, method for preparing the same, and anti-allergic agent | |
US3658829A (en) | Phenoxy carboxylic acid derivatives | |
JPS63275561A (ja) | 置換ピロール類 | |
CN103030631B (zh) | 用于制备嘧啶二酮类dpp-iv抑制剂的化合物 | |
RU2639875C2 (ru) | Производное фенила | |
CN107922375A (zh) | 靶向idh2突变的抗肿瘤化合物及其使用方法 | |
TWI676625B (zh) | 磺醯胺類衍生物、其製備方法及其在醫藥上的用途 | |
JPH01261377A (ja) | 置換されたピリミジン | |
KR100431789B1 (ko) | 신규한벤조티아졸유도체 | |
JPS6399057A (ja) | グリシン誘導体 | |
JP2876144B2 (ja) | 3―フェニルクマリン―7―イルオキシ酢酸誘導体とその製法及び用途 | |
CN102442997B (zh) | 一类喹啉衍生物、其制备方法、中间体及其应用 | |
CN102079726A (zh) | 一类嘧啶类化合物及其中间体、制备方法和应用 | |
JP5702778B2 (ja) | 結晶型iのロスバスタチン亜鉛塩 | |
CN113698383B (zh) | 一种哌嗪类化合物及其应用 | |
JPH01261375A (ja) | 置換イミダゾリノン類又はイミダゾリチオン類 | |
CN102786553B (zh) | 一种葡萄糖醛酸苷类化合物的纯化方法 | |
EP0334147A1 (de) | Disubstituierte Pyrrole | |
JP3190717B2 (ja) | 新規な置換イタコン酸誘導体 | |
JP3003038B2 (ja) | 新規なイソクマリン誘導体とその製法及び用途 | |
JPH0586392B2 (zh) | ||
CN107663202B (zh) | 3-(脲基-甲基)-4-芳基-吡啶衍生物及其制备方法和作为抗肝癌药物的应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
ASS | Succession or assignment of patent right |
Owner name: SHENZHEN SALUBRIS PHARMACEUTICALS CO., LTD. |
|
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20100623 Address after: 200040 Beijing West Road, Shanghai, No. 1320 Applicant after: Shanghai Institute of pharmaceutical industry Co-applicant after: Shenzhen Salubris Pharmaceuticals Co., Ltd. Address before: 200040 Beijing West Road, Shanghai, No. 1320 Applicant before: Shanghai Institute of pharmaceutical industry |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C56 | Change in the name or address of the patentee | ||
CP03 | Change of name, title or address |
Address after: 200040 Beijing West Road, Shanghai, No. 1320 Co-patentee after: Shenzhen Salubris Pharmaceuticals Co., Ltd. Patentee after: Shanghai Institute of pharmaceutical industry Address before: 200040 Beijing West Road, Shanghai, No. 1320 Co-patentee before: Shenzhen Salubris Pharmaceuticals Co., Ltd. Patentee before: Shanghai Institute of pharmaceutical industry |
|
ASS | Succession or assignment of patent right |
Free format text: FORMER OWNER: SHENZHEN SALUBRIS PHARMACEUTICALS CO., LTD. Effective date: 20140730 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20140730 Address after: 200040 Beijing West Road, Shanghai, No. 1320 Patentee after: Shanghai Institute of pharmaceutical industry Address before: 200040 Beijing West Road, Shanghai, No. 1320 Patentee before: Shanghai Institute of pharmaceutical industry Patentee before: Shenzhen Salubris Pharmaceuticals Co., Ltd. |
|
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110831 Termination date: 20170430 |