IL123939A - The history of the heterocycles and the pharmaceutical preparations containing them - Google Patents
The history of the heterocycles and the pharmaceutical preparations containing themInfo
- Publication number
- IL123939A IL123939A IL12393996A IL12393996A IL123939A IL 123939 A IL123939 A IL 123939A IL 12393996 A IL12393996 A IL 12393996A IL 12393996 A IL12393996 A IL 12393996A IL 123939 A IL123939 A IL 123939A
- Authority
- IL
- Israel
- Prior art keywords
- formula
- alkyl
- group
- hydrogen atom
- carboxy
- Prior art date
Links
- 125000000623 heterocyclic group Chemical group 0.000 title claims description 29
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 169
- -1 hydroxy, carboxy Chemical group 0.000 claims abstract description 88
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 60
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 43
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 38
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 32
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 32
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 29
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 23
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims abstract description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 19
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 17
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 180
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 239000003112 inhibitor Substances 0.000 claims description 10
- NJXHWJBPZDZTSA-UHFFFAOYSA-N 2-[7-(2,2-dimethylpropanoylamino)-1-hexyl-4,6-dimethyl-2,3-dihydroindol-5-yl]acetic acid Chemical compound CC(C)(C)C(=O)NC1=C(C)C(CC(O)=O)=C(C)C2=C1N(CCCCCC)CC2 NJXHWJBPZDZTSA-UHFFFAOYSA-N 0.000 claims description 2
- ZLKLYKRETIYWEH-UHFFFAOYSA-N 2-[7-(2,2-dimethylpropanoylamino)-4,6-dimethyl-1-nonyl-2,3-dihydroindol-5-yl]acetic acid Chemical compound CC(C)(C)C(=O)NC1=C(C)C(CC(O)=O)=C(C)C2=C1N(CCCCCCCCC)CC2 ZLKLYKRETIYWEH-UHFFFAOYSA-N 0.000 claims description 2
- XOLXWYYLSMAHML-UHFFFAOYSA-N 7-(2,2-dimethylpropanoylamino)-1-hexyl-4,6-dimethyl-2,3-dihydroindole-5-carboxylic acid Chemical compound CC(C)(C)C(=O)NC1=C(C)C(C(O)=O)=C(C)C2=C1N(CCCCCC)CC2 XOLXWYYLSMAHML-UHFFFAOYSA-N 0.000 claims description 2
- NJOLVEUREMBWSS-UHFFFAOYSA-N 7-(2,2-dimethylpropanoylamino)-1-hexyl-6-methyl-2,3-dihydroindole-5-carboxylic acid Chemical compound OC(=O)C1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCC)CCC2=C1 NJOLVEUREMBWSS-UHFFFAOYSA-N 0.000 claims description 2
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 claims description 2
- 108010054082 Sterol O-acyltransferase Proteins 0.000 claims description 2
- FAHGIPNMBZNSQT-UHFFFAOYSA-N n-[1-heptyl-5-(hydroxymethyl)-6-methyl-2,3-dihydroindol-7-yl]-2,2-dimethylpropanamide Chemical compound OCC1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCCC)CCC2=C1 FAHGIPNMBZNSQT-UHFFFAOYSA-N 0.000 claims description 2
- CSVDSOYLFYDPHC-UHFFFAOYSA-N n-[1-hexyl-5-(hydroxymethyl)-4,6-dimethyl-2,3-dihydroindol-7-yl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=C(C)C(CO)=C(C)C2=C1N(CCCCCC)CC2 CSVDSOYLFYDPHC-UHFFFAOYSA-N 0.000 claims description 2
- DOOVELNTJTWRLR-UHFFFAOYSA-N n-[1-hexyl-5-(hydroxymethyl)-6-methyl-2,3-dihydroindol-7-yl]-2,2-dimethylpropanamide Chemical compound OCC1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCC)CCC2=C1 DOOVELNTJTWRLR-UHFFFAOYSA-N 0.000 claims 2
- NEBXOJUGEJYVSC-UHFFFAOYSA-N 1-decyl-7-(2,2-dimethylpropanoylamino)-6-methyl-2,3-dihydroindole-5-carboxylic acid Chemical compound OC(=O)C1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCCCCCC)CCC2=C1 NEBXOJUGEJYVSC-UHFFFAOYSA-N 0.000 claims 1
- HWSGILMMJJTFMU-UHFFFAOYSA-N 2-[1-decyl-8-(2,2-dimethylpropanoylamino)-5,7-dimethyl-3,4-dihydro-2h-quinolin-6-yl]acetic acid Chemical compound OC(=O)CC1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCCCCCC)CCCC2=C1C HWSGILMMJJTFMU-UHFFFAOYSA-N 0.000 claims 1
- RJXJBDKYMWQPJK-UHFFFAOYSA-N 2-[7-(2,2-dimethylpropanoylamino)-1-heptyl-4,6-dimethyl-2,3-dihydroindol-5-yl]acetic acid Chemical compound CC(C)(C)C(=O)NC1=C(C)C(CC(O)=O)=C(C)C2=C1N(CCCCCCC)CC2 RJXJBDKYMWQPJK-UHFFFAOYSA-N 0.000 claims 1
- ZDDNMAAPDPYBCD-UHFFFAOYSA-N 2-[8-(2,2-dimethylpropanoylamino)-1-hexyl-5,7-dimethyl-3,4-dihydro-2h-quinolin-6-yl]acetic acid Chemical compound OC(=O)CC1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCC)CCCC2=C1C ZDDNMAAPDPYBCD-UHFFFAOYSA-N 0.000 claims 1
- 229940123324 Acyltransferase inhibitor Drugs 0.000 claims 1
- 239000002404 acyltransferase inhibitor Substances 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- VPLZHSYSHAERMW-UHFFFAOYSA-N n-[1-heptyl-5-(hydroxymethyl)-4,6-dimethyl-2,3-dihydroindol-7-yl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=C(C)C(CO)=C(C)C2=C1N(CCCCCCC)CC2 VPLZHSYSHAERMW-UHFFFAOYSA-N 0.000 claims 1
- GFYWDRZYNDOEGN-UHFFFAOYSA-N n-[1-heptyl-6-(hydroxymethyl)-5,7-dimethyl-3,4-dihydro-2h-quinolin-8-yl]-2,2-dimethylpropanamide Chemical compound OCC1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCCC)CCCC2=C1C GFYWDRZYNDOEGN-UHFFFAOYSA-N 0.000 claims 1
- JFXCKNSAIFYTDF-UHFFFAOYSA-N n-[1-hexyl-6-(hydroxymethyl)-5,7-dimethyl-3,4-dihydro-2h-quinolin-8-yl]-2,2-dimethylpropanamide Chemical compound OCC1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCC)CCCC2=C1C JFXCKNSAIFYTDF-UHFFFAOYSA-N 0.000 claims 1
- SVCDYHQBKQTGND-UHFFFAOYSA-N n-[6-(hydroxymethyl)-5,7-dimethyl-1-nonyl-3,4-dihydro-2h-quinolin-8-yl]-2,2-dimethylpropanamide Chemical compound OCC1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCCCCC)CCCC2=C1C SVCDYHQBKQTGND-UHFFFAOYSA-N 0.000 claims 1
- 230000002248 lipoperoxidative effect Effects 0.000 abstract description 15
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 131
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 119
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 116
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 103
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 85
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 82
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
- 239000000203 mixture Substances 0.000 description 77
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 63
- 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 46
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
- 239000003480 eluent Substances 0.000 description 41
- 239000010410 layer Substances 0.000 description 40
- 238000010898 silica gel chromatography Methods 0.000 description 40
- 238000000034 method Methods 0.000 description 39
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 38
- 238000003756 stirring Methods 0.000 description 36
- 239000000243 solution Substances 0.000 description 33
- 238000004519 manufacturing process Methods 0.000 description 32
- 101150041968 CDC13 gene Proteins 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 28
- 238000005160 1H NMR spectroscopy Methods 0.000 description 27
- 239000002904 solvent Substances 0.000 description 25
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- 230000002401 inhibitory effect Effects 0.000 description 21
- 238000005406 washing Methods 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- 125000006239 protecting group Chemical group 0.000 description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- 235000012000 cholesterol Nutrition 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
- ZYFOYQCUCOCLLT-UHFFFAOYSA-N methyl 3-[7-(2,2-dimethylpropanoylamino)-4,6-dimethyl-1-octyl-2,3-dihydroindol-3-yl]propanoate Chemical compound CC(C)(C)C(=O)NC1=C(C)C=C(C)C2=C1N(CCCCCCCC)CC2CCC(=O)OC ZYFOYQCUCOCLLT-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 13
- 239000002253 acid Substances 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 239000005457 ice water Substances 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- 230000001603 reducing effect Effects 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 230000002378 acidificating effect Effects 0.000 description 10
- 208000011775 arteriosclerosis disease Diseases 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 206010003210 Arteriosclerosis Diseases 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 8
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- FMLJREWZCZHGGW-UHFFFAOYSA-N 1-cycloheptyl-1-(9h-fluoren-2-ylmethyl)-3-(2,4,6-trimethylphenyl)urea Chemical compound CC1=CC(C)=CC(C)=C1NC(=O)N(C1CCCCCC1)CC1=CC=C2C3=CC=CC=C3CC2=C1 FMLJREWZCZHGGW-UHFFFAOYSA-N 0.000 description 7
- UWLHSHAHTBJTBA-UHFFFAOYSA-N 1-iodooctane Chemical compound CCCCCCCCI UWLHSHAHTBJTBA-UHFFFAOYSA-N 0.000 description 7
- 244000215068 Acacia senegal Species 0.000 description 7
- 229920000084 Gum arabic Polymers 0.000 description 7
- 239000000205 acacia gum Substances 0.000 description 7
- 235000010489 acacia gum Nutrition 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 150000001840 cholesterol esters Chemical class 0.000 description 6
- 229940118019 malondialdehyde Drugs 0.000 description 6
- 239000008177 pharmaceutical agent Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 210000000813 small intestine Anatomy 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229910017604 nitric acid Inorganic materials 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 210000004400 mucous membrane Anatomy 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- 206010002091 Anaesthesia Diseases 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- RJECHNNFRHZQKU-UHFFFAOYSA-N Oelsaeurecholesterylester Natural products C12CCC3(C)C(C(C)CCCC(C)C)CCC3C2CC=C2C1(C)CCC(OC(=O)CCCCCCCC=CCCCCCCCC)C2 RJECHNNFRHZQKU-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- RJECHNNFRHZQKU-RMUVNZEASA-N cholesteryl oleate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)C1 RJECHNNFRHZQKU-RMUVNZEASA-N 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
- JANLGRVMMWYCQL-UHFFFAOYSA-N ethyl 2-[7-(2,2-dimethylpropanoylamino)-4,6-dimethyl-2,3-dihydro-1h-indol-5-yl]acetate Chemical compound CC(C)(C)C(=O)NC1=C(C)C(CC(=O)OCC)=C(C)C2=C1NCC2 JANLGRVMMWYCQL-UHFFFAOYSA-N 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
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- UKTGKQOSMNZKIC-UHFFFAOYSA-N n-(1-hexyl-5-hydroxy-2,6-dimethyl-2,3-dihydroindol-7-yl)-2,2-dimethylpropanamide Chemical compound OC1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCC)C(C)CC2=C1 UKTGKQOSMNZKIC-UHFFFAOYSA-N 0.000 description 1
- QAKJXJZBXCVFLX-UHFFFAOYSA-N n-(diaminomethylidene)-1h-indole-2-carboxamide Chemical class C1=CC=C2NC(C(=O)N=C(N)N)=CC2=C1 QAKJXJZBXCVFLX-UHFFFAOYSA-N 0.000 description 1
- DSDBDTZBWMVGIO-UHFFFAOYSA-N n-[1-acetyl-5-(cyanomethyl)-4,6-dimethyl-2,3-dihydroindol-7-yl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=C(C)C(CC#N)=C(C)C2=C1N(C(=O)C)CC2 DSDBDTZBWMVGIO-UHFFFAOYSA-N 0.000 description 1
- QAKOWWVVXMISPS-UHFFFAOYSA-N n-[1-acetyl-5-[(dimethylamino)methyl]-4,6-dimethyl-2,3-dihydroindol-7-yl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=C(C)C(CN(C)C)=C(C)C2=C1N(C(C)=O)CC2 QAKOWWVVXMISPS-UHFFFAOYSA-N 0.000 description 1
- PXUSVYFEHLCDMK-UHFFFAOYSA-N n-[3-(2-hydroxyethyl)-4,6-dimethyl-1-octyl-2,3-dihydroindol-7-yl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=C(C)C=C(C)C2=C1N(CCCCCCCC)CC2CCO PXUSVYFEHLCDMK-UHFFFAOYSA-N 0.000 description 1
- JBBSFMFUMBWOMI-UHFFFAOYSA-N n-[3-(2-hydroxyethyl)-4,6-dimethyl-2,3-dihydro-1h-indol-7-yl]-2,2-dimethylpropanamide Chemical compound CC1=CC(C)=C(NC(=O)C(C)(C)C)C2=C1C(CCO)CN2 JBBSFMFUMBWOMI-UHFFFAOYSA-N 0.000 description 1
- NFUQSVMUYMQKTH-UHFFFAOYSA-N n-[5-(2-chloroethyl)-4,6-dimethyl-1-octyl-2,3-dihydroindol-7-yl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=C(C)C(CCCl)=C(C)C2=C1N(CCCCCCCC)CC2 NFUQSVMUYMQKTH-UHFFFAOYSA-N 0.000 description 1
- LKSSLXJPFCMBMX-UHFFFAOYSA-N n-[5-(2-cyanoethyl)-4,6-dimethyl-1-octyl-2,3-dihydroindol-7-yl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=C(C)C(CCC#N)=C(C)C2=C1N(CCCCCCCC)CC2 LKSSLXJPFCMBMX-UHFFFAOYSA-N 0.000 description 1
- JELRDLXTYPXWEB-UHFFFAOYSA-N n-[5-(hydroxymethyl)-6-methyl-1-octyl-2,3-dihydroindol-7-yl]-2,2-dimethylpropanamide Chemical compound OCC1=C(C)C(NC(=O)C(C)(C)C)=C2N(CCCCCCCC)CCC2=C1 JELRDLXTYPXWEB-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001196 nonadecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([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
- 125000001400 nonyl 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])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000000913 palmityl 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])C([H])([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
- 125000002958 pentadecyl 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])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
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000005930 sec-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- DIORMHZUUKOISG-UHFFFAOYSA-N sulfoformic acid Chemical group OC(=O)S(O)(=O)=O DIORMHZUUKOISG-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000002889 tridecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl 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])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25908295 | 1995-10-05 | ||
| JP5801896 | 1996-03-14 | ||
| JP19433196 | 1996-07-24 | ||
| PCT/JP1996/002852 WO1997012860A1 (fr) | 1995-10-05 | 1996-09-30 | Nouveaux derives heterocycliques et leur utilisation medicinale |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL123939A true IL123939A (en) | 2001-11-25 |
Family
ID=27296460
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL12393996A IL123939A (en) | 1995-10-05 | 1996-09-30 | The history of the heterocycles and the pharmaceutical preparations containing them |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | USRE38970E1 (cs) |
| EP (1) | EP0866059B1 (cs) |
| KR (1) | KR100388345B1 (cs) |
| CN (2) | CN1097043C (cs) |
| AT (1) | ATE210116T1 (cs) |
| BR (1) | BR9610846A (cs) |
| CZ (1) | CZ292632B6 (cs) |
| DE (1) | DE69617731T2 (cs) |
| DK (1) | DK0866059T3 (cs) |
| ES (1) | ES2164920T3 (cs) |
| HK (1) | HK1048989B (cs) |
| HU (1) | HUP9900617A3 (cs) |
| IL (1) | IL123939A (cs) |
| NO (1) | NO310818B1 (cs) |
| NZ (1) | NZ318874A (cs) |
| PL (1) | PL190034B1 (cs) |
| PT (1) | PT866059E (cs) |
| TR (1) | TR199800655T2 (cs) |
| TW (1) | TW429250B (cs) |
| WO (1) | WO1997012860A1 (cs) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP3720395B2 (ja) * | 1994-09-20 | 2005-11-24 | 京都薬品工業株式会社 | 新規ヘテロ環誘導体、その製造方法およびその医薬用途 |
| AR008331A1 (es) * | 1997-01-23 | 1999-12-29 | Smithkline Beecham Corp | Compuestos antagonistas de un receptor de il-8, uso de los mismos para la fabricacion de medicamentos, procedimiento para su obtencion, composicionesfarmaceuticas que los contienen |
| US5929250A (en) * | 1997-01-23 | 1999-07-27 | Smithkline Beecham Corporation | IL-8 receptor antagonists |
| AR015425A1 (es) * | 1997-09-05 | 2001-05-02 | Smithkline Beecham Corp | Compuestos de benzotiazol, composicion farmaceutica que los contiene, su uso en la manufactura de un medicamento, procedimiento para su preparacion,compuestos intermediarios y procedimiento para su preparacion |
| CA2327695A1 (en) * | 1998-04-08 | 1999-10-21 | Takeda Chemical Industries, Ltd. | Amine compounds, their production and their use as somatostatin receptor antagonists or agonists |
| BR9815951A (pt) * | 1998-07-23 | 2001-03-06 | Smithkline Beecham Corp | Antagonistas do receptor de il-8 |
| FR2783519B1 (fr) | 1998-09-23 | 2003-01-24 | Sod Conseils Rech Applic | Nouveaux derives d'amidines, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
| NZ524406A (en) * | 2000-09-01 | 2004-06-25 | Sankyo Co | Medicinal compositions containing HMG-CoA reductase inhibitor and ACAT inhibitor |
| TW200600497A (en) * | 2001-02-02 | 2006-01-01 | Sankyo Co | Preparation of indoline derivative |
| WO2002072147A1 (fr) * | 2001-03-14 | 2002-09-19 | Sankyo Company, Limited | Compositions medicinales contenant un inhibiteur de transporteur d'acide biliaire |
| EP2335700A1 (en) * | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C virus polymerase inhibitors with a heterobicylic structure |
| MXPA04001878A (es) * | 2001-08-28 | 2004-06-15 | Sankyo Co | Composiciones medicinales que comprenden antagonista del receptor de angiotensina ii. |
| JP2004002365A (ja) * | 2002-04-05 | 2004-01-08 | Sankyo Co Ltd | Ａｃａｔ阻害剤とインシュリン抵抗性改善剤とからなる医薬組成物 |
| EP1493448A4 (en) * | 2002-04-05 | 2007-12-05 | Sankyo Co | MEDICAL COMPOSITION WITH ACAT HEMMER AND AGENT TO IMPROVE INSULIN RESISTANCE |
| US20050119314A1 (en) * | 2002-04-05 | 2005-06-02 | Sankyo Company, Limited | Pharmaceutical composition comprising an ACAT inhibitor and an insulin resistance reducing agent |
| ZA200501297B (en) * | 2002-07-17 | 2006-10-25 | Kyoto Pharma Ind | Novel indoline compound and medicinal use thereof |
| US20050192245A1 (en) * | 2002-07-18 | 2005-09-01 | Sankyo Company, Limited | Medicinal composition for treating arteriosclerosis |
| IL166312A0 (en) * | 2002-07-18 | 2006-01-15 | Sankyo Co | A pharmaceutical composition containing an adp receptor antagonist and an acat inhibitor |
| US7223785B2 (en) * | 2003-01-22 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| US7098231B2 (en) * | 2003-01-22 | 2006-08-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| EP2428516A1 (en) | 2003-11-19 | 2012-03-14 | Metabasis Therapeutics, Inc. | Novel phosphorus-containing thyromimetics |
| WO2005077359A1 (ja) * | 2004-02-17 | 2005-08-25 | Sankyo Company, Limited | インドリン化合物を含有する安定化された医薬組成物 |
| KR20120091276A (ko) * | 2004-02-20 | 2012-08-17 | 베링거 인겔하임 인터내셔날 게엠베하 | 바이러스 폴리머라제 억제제 |
| AU2005294165B2 (en) | 2004-10-06 | 2012-02-02 | The Brigham And Women's Hospital, Inc. | Relevance of achieved levels of markers of systemic inflammation following treatment |
| RU2007115900A (ru) * | 2004-10-27 | 2008-11-10 | Дайити Санкио Компани, Лимитед (Jp) | Производные бензола, имеющие 2 или более заместителей |
| EP1915378A4 (en) * | 2005-08-12 | 2009-07-22 | Boehringer Ingelheim Int | VIRUS POLYMERASE INHIBITORS |
| WO2007146230A2 (en) * | 2006-06-14 | 2007-12-21 | Merck & Co., Inc. | Non-nucleoside reverse transcriptase inhibitors |
| FR2918890A1 (fr) * | 2007-07-19 | 2009-01-23 | Galderma Res & Dev | Utilisation du pactimibe pour la preparation d'un medicament destine a prevenir ou a traiter une maladie due a un dysfonctionnement des glandes sebacees chez l'homme ou l'animal |
| WO2010093601A1 (en) | 2009-02-10 | 2010-08-19 | Metabasis Therapeutics, Inc. | Novel sulfonic acid-containing thyromimetics, and methods for their use |
| US8343706B2 (en) | 2010-01-25 | 2013-01-01 | International Business Machines Corporation | Fluorine-free fused ring heteroaromatic photoacid generators and resist compositions containing the same |
| WO2011161964A1 (ja) * | 2010-06-24 | 2011-12-29 | 興和株式会社 | Ａｃａｔ阻害剤を有効成分とするインスリン抵抗性改善剤 |
| US9650375B2 (en) | 2013-03-14 | 2017-05-16 | Merck Sharp & Dohme Corp. | Indole derivatives useful as anti-diabetic agents |
| JP2018052818A (ja) * | 2015-01-28 | 2018-04-05 | 武田薬品工業株式会社 | スルホンアミド化合物 |
| CN108440373B (zh) * | 2018-03-23 | 2021-05-14 | 昆明学院 | 一种铁催化的氰烷基吲哚啉及其制备方法 |
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| US4803218A (en) * | 1982-09-29 | 1989-02-07 | Mcneilab, Inc. | 3-aminoalkyl-1H-indole-5-urea and amide derivatives |
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| JPH02117651A (ja) * | 1988-01-20 | 1990-05-02 | Yamanouchi Pharmaceut Co Ltd | ジウレア誘導体及びその製造法 |
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| US5153226A (en) * | 1989-08-31 | 1992-10-06 | Warner-Lambert Company | Acat inhibitors for treating hypocholesterolemia |
| FR2654335A1 (fr) | 1989-11-10 | 1991-05-17 | Oreal | Compositions tinctoriales pour fibres keratiniques contenant des precurseurs de colorants par oxydation et des coupleurs derives du 4-hydroxyindole, et procede de teinture les mettant en óoeuvre. |
| EP0447116B1 (en) * | 1990-03-12 | 1994-12-14 | Yamanouchi Pharmaceutical Co. Ltd. | Urea derivatives, their production, and pharmaceutical compositions containing them |
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| GB9025848D0 (en) | 1990-11-28 | 1991-01-09 | Erba Carlo Spa | Imidazol-2-yl derivatives of substituted bicyclic compounds and process for their preparation |
| FR2673625B1 (fr) * | 1991-03-08 | 1993-05-07 | Adir | Nouveaux derives d'acylaminophenol, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| FR2674522B1 (fr) * | 1991-03-26 | 1993-07-16 | Lipha | Nouveaux derives de l'indole, procedes de preparation et medicaments les contenant. |
| IL101785A0 (en) * | 1991-05-10 | 1992-12-30 | Fujisawa Pharmaceutical Co | Urea derivatives,processes for the preparation thereof and pharmaceutical compositions containing the same |
| CN1068000A (zh) * | 1991-06-27 | 1993-01-13 | 重庆人民广播电台 | 动平衡开关调幅浮动载波广播电视发射机 |
| CA2121391A1 (en) * | 1993-04-28 | 1994-10-29 | Atsuyuki Kojima | Indoloylguanidine derivatives |
| US5952354A (en) | 1993-07-21 | 1999-09-14 | American Home Products Corporation | Tris carbamic acid esters: inhibitors of cholesterol absorption |
| JP3720395B2 (ja) * | 1994-09-20 | 2005-11-24 | 京都薬品工業株式会社 | 新規ヘテロ環誘導体、その製造方法およびその医薬用途 |
| JPH08208602A (ja) * | 1994-10-18 | 1996-08-13 | Sumitomo Pharmaceut Co Ltd | インドロイルグアニジン誘導体 |
| CA2160600A1 (en) * | 1994-10-18 | 1996-04-19 | Masahumi Kitano | Indoloylguanidine derivatives |
| US5767129A (en) * | 1995-08-24 | 1998-06-16 | Warner-Lambert Company | Substituted quinolines and isoquinolines as calcium channel blockers, their preparation and the use thereof |
| US5994040A (en) * | 1996-03-04 | 1999-11-30 | Fuji Photo Film Co., Ltd. | Processing composition for silver halide photographic light-sensitive material, developer and processing method using the same |
-
1996
- 1996-09-30 US US10/609,224 patent/USRE38970E1/en not_active Expired - Fee Related
- 1996-09-30 PL PL96326000A patent/PL190034B1/pl not_active IP Right Cessation
- 1996-09-30 EP EP96932060A patent/EP0866059B1/en not_active Expired - Lifetime
- 1996-09-30 TR TR1998/00655T patent/TR199800655T2/xx unknown
- 1996-09-30 US US09/051,202 patent/US6063806A/en not_active Ceased
- 1996-09-30 PT PT96932060T patent/PT866059E/pt unknown
- 1996-09-30 HU HU9900617A patent/HUP9900617A3/hu unknown
- 1996-09-30 IL IL12393996A patent/IL123939A/en not_active IP Right Cessation
- 1996-09-30 CZ CZ1998996A patent/CZ292632B6/cs not_active IP Right Cessation
- 1996-09-30 ES ES96932060T patent/ES2164920T3/es not_active Expired - Lifetime
- 1996-09-30 DK DK96932060T patent/DK0866059T3/da active
- 1996-09-30 AT AT96932060T patent/ATE210116T1/de not_active IP Right Cessation
- 1996-09-30 NZ NZ318874A patent/NZ318874A/xx unknown
- 1996-09-30 KR KR10-1998-0702462A patent/KR100388345B1/ko not_active Expired - Fee Related
- 1996-09-30 DE DE69617731T patent/DE69617731T2/de not_active Expired - Fee Related
- 1996-09-30 CN CN96198670A patent/CN1097043C/zh not_active Expired - Fee Related
- 1996-09-30 WO PCT/JP1996/002852 patent/WO1997012860A1/ja active IP Right Grant
- 1996-09-30 BR BR9610846A patent/BR9610846A/pt not_active IP Right Cessation
- 1996-10-04 TW TW085112125A patent/TW429250B/zh not_active IP Right Cessation
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1998
- 1998-04-01 NO NO19981485A patent/NO310818B1/no unknown
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1999
- 1999-03-05 HK HK03100740.0A patent/HK1048989B/zh not_active IP Right Cessation
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2000
- 2000-02-18 US US09/506,839 patent/US6200988B1/en not_active Expired - Fee Related
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2001
- 2001-11-30 CN CNB011429577A patent/CN1193018C/zh not_active Expired - Fee Related
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