JP5964965B2 - コレステリルエステル転送タンパク質（ｃｅｔｐ）インヒビターとしての置換複素環式アミン化合物 - Google Patents
コレステリルエステル転送タンパク質（ｃｅｔｐ）インヒビターとしての置換複素環式アミン化合物 Download PDFInfo
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- JP5964965B2 JP5964965B2 JP2014525513A JP2014525513A JP5964965B2 JP 5964965 B2 JP5964965 B2 JP 5964965B2 JP 2014525513 A JP2014525513 A JP 2014525513A JP 2014525513 A JP2014525513 A JP 2014525513A JP 5964965 B2 JP5964965 B2 JP 5964965B2
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- Prior art keywords
- bis
- amino
- composition
- methyl
- trifluoromethyl
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- -1 heterocyclic amine compounds Chemical class 0.000 title claims description 91
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 title claims description 35
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 title claims description 35
- 239000003112 inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 136
- 150000003839 salts Chemical class 0.000 claims description 60
- 239000000203 mixture Substances 0.000 claims description 56
- 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 claims description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 108010010234 HDL Lipoproteins Proteins 0.000 claims description 29
- 102000015779 HDL Lipoproteins Human genes 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 108010007622 LDL Lipoproteins Proteins 0.000 claims description 18
- 102000007330 LDL Lipoproteins Human genes 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 235000012000 cholesterol Nutrition 0.000 claims description 15
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- RQOAFNHVMUEZCR-UHFFFAOYSA-N 1-[2-[[2-[bis(cyclopropylmethyl)amino]-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-3-yl]methyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]pyrimidin-5-yl]ethanone Chemical compound N1=CC(C(=O)C)=CN=C1N(CC=1C(=NC=2C(C)(C)CCC=2C=1)N(CC1CC1)CC1CC1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 RQOAFNHVMUEZCR-UHFFFAOYSA-N 0.000 claims description 4
- KSCIRGBOZOOCGR-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(5-bromopyrimidin-2-yl)amino]methyl]-n,n-bis(cyclopropylmethyl)-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-2-amine Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)(C)CCC2=CC=1CN(C=1N=CC(Br)=CN=1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 KSCIRGBOZOOCGR-UHFFFAOYSA-N 0.000 claims description 4
- FPNOEWBPBGITIG-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(5-morpholin-4-ylpyrimidin-2-yl)amino]methyl]-n,n-bis(cyclopropylmethyl)-7-methyl-6,7-dihydro-5h-cyclopenta[b]pyridin-2-amine Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)CCC2=CC=1CN(C=1N=CC(=CN=1)N1CCOCC1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FPNOEWBPBGITIG-UHFFFAOYSA-N 0.000 claims description 4
- RUTYCHVMQPWNIE-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(5-morpholin-4-ylpyrimidin-2-yl)amino]methyl]-n,n-bis(cyclopropylmethyl)-8-methyl-5,6,7,8-tetrahydroquinolin-2-amine Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)CCCC2=CC=1CN(C=1N=CC(=CN=1)N1CCOCC1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 RUTYCHVMQPWNIE-UHFFFAOYSA-N 0.000 claims description 4
- GZHXEBSHPZKQQD-UHFFFAOYSA-N 6-[[2-[bis(cyclopropylmethyl)amino]-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-3-yl]methyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-3h-1,3-benzoxazol-2-one Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)(C)CCC2=CC=1CN(C=1C=C2OC(=O)NC2=CC=1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GZHXEBSHPZKQQD-UHFFFAOYSA-N 0.000 claims description 4
- QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 claims description 4
- XOQVOMVOQSRTBT-UHFFFAOYSA-N 1-[2-[[2-[bis(cyclopropylmethyl)amino]-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-3-yl]methyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]pyrimidin-5-yl]pyrrolidin-2-one Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)(C)CCC2=CC=1CN(C=1N=CC(=CN=1)N1C(CCC1)=O)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XOQVOMVOQSRTBT-UHFFFAOYSA-N 0.000 claims description 3
- GSPJRPLWSWFKSX-UHFFFAOYSA-N 2-[[2-[bis(cyclopropylmethyl)amino]-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-3-yl]methyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]pyrimidine-5-carbonitrile Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)(C)CCC2=CC=1CN(C=1N=CC(=CN=1)C#N)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GSPJRPLWSWFKSX-UHFFFAOYSA-N 0.000 claims description 3
- FPTZHWFBRGUFAQ-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(5-morpholin-4-ylpyrimidin-2-yl)amino]methyl]-n,n-bis(cyclopropylmethyl)-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-2-amine Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)(C)CCC2=CC=1CN(C=1N=CC(=CN=1)N1CCOCC1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FPTZHWFBRGUFAQ-UHFFFAOYSA-N 0.000 claims description 3
- FBDMWMAWNPVGTQ-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-[5-(1,2-oxazol-3-yl)pyrimidin-2-yl]amino]methyl]-n,n-bis(cyclopropylmethyl)-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-2-amine Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)(C)CCC2=CC=1CN(C=1N=CC(=CN=1)C1=NOC=C1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FBDMWMAWNPVGTQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- RSLJQTLOULWAGO-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-[5-(1h-pyrazol-5-yl)pyrimidin-2-yl]amino]methyl]-n,n-bis(cyclopropylmethyl)-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-2-amine Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)(C)CCC2=CC=1CN(C=1N=CC(=CN=1)C1=NNC=C1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 RSLJQTLOULWAGO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
- 238000000034 method Methods 0.000 description 55
- 125000000217 alkyl group Chemical group 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 125000003545 alkoxy group Chemical group 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- 125000001188 haloalkyl group Chemical group 0.000 description 23
- 230000002829 reductive effect Effects 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- 238000003786 synthesis reaction Methods 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000000463 material Substances 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 239000012267 brine Substances 0.000 description 16
- 238000004440 column chromatography Methods 0.000 description 16
- 125000000753 cycloalkyl group Chemical group 0.000 description 16
- 239000003208 petroleum Substances 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- 125000004438 haloalkoxy group Chemical group 0.000 description 14
- 125000000623 heterocyclic group Chemical group 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 12
- 125000001072 heteroaryl group Chemical group 0.000 description 12
- 150000002431 hydrogen Chemical class 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 7
- 201000001320 Atherosclerosis Diseases 0.000 description 7
- 125000002252 acyl group Chemical group 0.000 description 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 108010023302 HDL Cholesterol Proteins 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 235000017550 sodium carbonate Nutrition 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- ZIXLDMFVRPABBX-UHFFFAOYSA-N 2-methylcyclopentan-1-one Chemical compound CC1CCCC1=O ZIXLDMFVRPABBX-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 4
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 238000008214 LDL Cholesterol Methods 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 208000029078 coronary artery disease Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 3
- OMPGFLIDZNVDQZ-UHFFFAOYSA-N 2-[bis(cyclopropylmethyl)amino]-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridine-3-carbaldehyde Chemical compound N1=C2C(C)(C)CCC2=CC(C=O)=C1N(CC1CC1)CC1CC1 OMPGFLIDZNVDQZ-UHFFFAOYSA-N 0.000 description 3
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 3
- LYRUJPZLAPXETM-UHFFFAOYSA-N 3,4-dimethyl-6,7-dihydro-5H-cyclopenta[b]pyridin-2-amine Chemical compound CC1=C2C(=NC(=C1C)N)CCC2 LYRUJPZLAPXETM-UHFFFAOYSA-N 0.000 description 3
- HIADNDIYKJVIRB-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]methyl]-n,n-bis(cyclopropylmethyl)-8,8-dimethyl-6,7-dihydro-5h-quinolin-2-amine Chemical compound CN1N=NC(N(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CC=2C(=NC=3C(C)(C)CCCC=3C=2)N(CC2CC2)CC2CC2)=N1 HIADNDIYKJVIRB-UHFFFAOYSA-N 0.000 description 3
- IDFXBZVTEAFXAA-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-[2-(2-methylpropyl)tetrazol-5-yl]amino]methyl]-n,n-bis(cyclopropylmethyl)-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-2-amine Chemical compound CC(C)CN1N=NC(N(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CC=2C(=NC=3C(C)(C)CCC=3C=2)N(CC2CC2)CC2CC2)=N1 IDFXBZVTEAFXAA-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
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- 102000004190 Enzymes Human genes 0.000 description 3
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- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
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- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 3
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
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- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000004141 reverse cholesterol transport Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2829CH2011 | 2011-08-18 | ||
| IN2829/CHE/2011 | 2011-08-18 | ||
| US201161557065P | 2011-11-08 | 2011-11-08 | |
| US61/557,065 | 2011-11-08 | ||
| PCT/IB2012/002056 WO2013024358A2 (en) | 2011-08-18 | 2012-08-17 | Substituted heterocyclic amine compounds as cholestryl ester-transfer protein (cetp) inhibitors |
Publications (3)
| Publication Number | Publication Date |
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| JP2014525929A JP2014525929A (ja) | 2014-10-02 |
| JP2014525929A5 JP2014525929A5 (cg-RX-API-DMAC7.html) | 2015-08-27 |
| JP5964965B2 true JP5964965B2 (ja) | 2016-08-03 |
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| JP2014525513A Expired - Fee Related JP5964965B2 (ja) | 2011-08-18 | 2012-08-17 | コレステリルエステル転送タンパク質（ｃｅｔｐ）インヒビターとしての置換複素環式アミン化合物 |
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| EP (1) | EP2744803A2 (cg-RX-API-DMAC7.html) |
| JP (1) | JP5964965B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR101774223B1 (cg-RX-API-DMAC7.html) |
| CN (1) | CN103827105B (cg-RX-API-DMAC7.html) |
| CA (1) | CA2845284C (cg-RX-API-DMAC7.html) |
| MX (1) | MX2014001849A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2013024358A2 (cg-RX-API-DMAC7.html) |
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| US9199967B2 (en) * | 2011-08-18 | 2015-12-01 | Dr. Reddy's Laboratories Ltd. | Substituted heterocyclic amine compounds as cholestryl ester-transfer protein (CETP) inhibitors |
| JPWO2014017569A1 (ja) * | 2012-07-26 | 2016-07-11 | 興和株式会社 | 血中ｌｄｌを低下させるための医薬 |
| EP4019521A4 (en) * | 2019-08-22 | 2023-05-03 | Blueray Therapeutics (Shanghai) Co., Ltd | AZAHETEROARYL COMPOUND AND USE |
Family Cites Families (107)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2965643A (en) | 1960-12-20 | Derivatives of pyrazolo | ||
| US2858309A (en) | 1956-05-07 | 1958-10-28 | Ciba Pharm Prod Inc | New aminobenzene sulfonamide |
| US3546295A (en) | 1968-08-01 | 1970-12-08 | Exxon Research Engineering Co | N-cycloalkyl anilines |
| DE3143016A1 (de) | 1980-10-29 | 1982-05-27 | Nippon Kayaku K.K., Tokyo | 5,6,7,8-tetrahydro-1,6-naphthyridinderivate und verfahren zu ihrer herstellung |
| DK288287A (da) * | 1986-06-09 | 1987-12-10 | Pfizer | Heterocycliske forbindelser samt farmaceutiske praeparater til behandling af allergiske eller inflammatoriske tilstande |
| JPH01104052A (ja) | 1987-06-12 | 1989-04-21 | Yoshitomi Pharmaceut Ind Ltd | ピリジン誘導体 |
| ES2058288T3 (es) | 1987-07-08 | 1994-11-01 | American Home Prod | Composiciones de ibuprofen secadas por atomizacion. |
| US5474989A (en) | 1988-11-11 | 1995-12-12 | Kurita Water Industries, Ltd. | Drug composition |
| US5260331A (en) | 1989-01-02 | 1993-11-09 | John Wyeth & Brother Limited | Composition for treating depression with (S- or O-heteroaryl)alkyl amines |
| AU641394B2 (en) | 1989-06-02 | 1993-09-23 | John Wyeth & Brother Limited | Amines |
| US5422355A (en) | 1989-06-02 | 1995-06-06 | John Wyeth & Brother, Limited | Composition for treating depression with (N-heteroaryl)alkylamines |
| WO1992018106A1 (fr) | 1991-04-16 | 1992-10-29 | Nippon Shinyaku Co., Ltd. | Procede de production d'une dispersion solide |
| WO1993000332A1 (en) | 1991-06-25 | 1993-01-07 | Merck & Co., Inc. | Substituted azetidinones as anti-inflammatory and antidegenerative agents |
| US5348953A (en) | 1991-06-25 | 1994-09-20 | Merck & Co., Inc. | Substituted azetidinones as anti-inflammatory and antidegenerative agents |
| TW225469B (cg-RX-API-DMAC7.html) | 1991-11-12 | 1994-06-21 | Nissan Kagakl Kogyo | |
| FR2686339B1 (fr) | 1992-01-22 | 1994-03-11 | Adir Cie | Nouveaux amides et sulfonamides naphtaleniques, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
| NO179904C (no) | 1992-09-04 | 1997-01-08 | Takeda Chemical Industries Ltd | Kondenserte heterocykliske forbindelser og deres anvendelse |
| EP0585500A1 (en) | 1992-09-04 | 1994-03-09 | Merrell Dow Pharmaceuticals Inc. | Diaryl piperazineacetamides as antimuscarinic agents |
| MY131441A (en) | 1992-12-29 | 2007-08-30 | American Cyanamid Co | Amidrazones and their use as insecticidal and acaricidal agents |
| DE69432019T2 (de) | 1993-08-12 | 2003-11-27 | Astrazeneca Ab, Soedertaelje | Amidin-derivate mit stickstoffoxid-synthease-aktivität |
| US5491152A (en) | 1994-03-23 | 1996-02-13 | The Du Pont Merck Pharmaceutical Company | Derivatives of cyclic ethers and sulfides for the treatment of atherosclerosis |
| JPH07285962A (ja) | 1994-04-20 | 1995-10-31 | Nissan Chem Ind Ltd | ピリジンカルボン酸アミド誘導体 |
| IT1270615B (it) | 1994-07-14 | 1997-05-07 | Smithkline Beecham Farma | Uso di derivati di chinolina |
| JPH0892224A (ja) | 1994-09-16 | 1996-04-09 | Kumiai Chem Ind Co Ltd | ３，５−置換フェニルトリアゾール誘導体および殺虫、殺ダニ剤 |
| JPH0892225A (ja) | 1994-09-29 | 1996-04-09 | Nissan Chem Ind Ltd | トリアゾールグリコール酸アミド誘導体 |
| EP0790057B1 (en) | 1994-11-29 | 2002-06-05 | Hisamitsu Pharmaceutical Co., Inc. | Antibacterial or bactericide comprising 2-aminothiazole derivative and salts thereof |
| GB9511220D0 (en) | 1995-06-02 | 1995-07-26 | Glaxo Group Ltd | Solid dispersions |
| US6730679B1 (en) | 1996-03-22 | 2004-05-04 | Smithkline Beecham Corporation | Pharmaceutical formulations |
| DE19615262A1 (de) | 1996-04-18 | 1997-10-23 | Bayer Ag | Heteroverknüpfte Phenylglycinolamide |
| IL124935A (en) | 1996-05-20 | 2001-06-14 | Janssen Pharmaceutica Nv | Dispersible antifungal compositions comprising itraconazole with improved bioavailability |
| AR008789A1 (es) | 1996-07-31 | 2000-02-23 | Bayer Corp | Piridinas y bifenilos substituidos |
| DE19636150A1 (de) | 1996-09-06 | 1998-03-12 | Asta Medica Ag | N-substituierte Indol-3-glyoxylamide mit antiasthmatischer, antiallergischer und immunsuppressiver/immunmodulierender Wirkung |
| TW523506B (en) | 1996-12-18 | 2003-03-11 | Ono Pharmaceutical Co | Sulfonamide or carbamide derivatives and drugs containing the same as active ingredients |
| AU7688398A (en) | 1997-06-16 | 1999-01-04 | American Home Products Corporation | Elevation of hdl cholesterol by 2-{(aminothioxomethyl)-hydrazono}-2-arylethyl carbamates |
| US6008362A (en) | 1997-06-16 | 1999-12-28 | Commons; Thomas Joseph | Elevation of HDL cholesterol by 2-(-4-chlorol-1-aryl-butylidene)-hydrazinecarbothioamides |
| US5977170A (en) | 1997-06-16 | 1999-11-02 | American Home Products Corporation | Elevation of HDL cholesterol by 4-[(aminothioxomethyl)hydrazono]-4-arylbutyl carbamates |
| WO1998057928A1 (en) | 1997-06-16 | 1998-12-23 | American Home Products Corporation | Elevation of hdl cholesterol by 2-(4-chloro -1-aryl-butylidene) -hydrazinecarbothioamides |
| AU7589498A (en) | 1997-06-16 | 1999-01-04 | American Home Products Corporation | Elevation of hdl cholesterol by 4-{(aminothioxomethyl)hydrazono}-4-arylbutyl carbamates |
| EP1745774A3 (en) | 1997-08-11 | 2007-04-11 | Pfizer Products Inc. | Solid pharmaceutical dispersions with enhanced bioavailability |
| UA67754C2 (uk) | 1997-10-10 | 2004-07-15 | Пфайзер, Інк. | Агоністи простагландину, фармацевтична композиція на їх основі (варіанти), спосіб нарощення та збереження кісткової маси у хребетних та спосіб лікування (варіанти) |
| JPH11209366A (ja) | 1998-01-23 | 1999-08-03 | Nissan Chem Ind Ltd | クロマン誘導体及び心不全治療薬 |
| DE19814838C2 (de) | 1998-04-02 | 2001-01-18 | Asta Medica Ag | Indolyl-3-glyoxylsäure-Derivate mit Antitumorwirkung |
| US6121271A (en) | 1998-05-12 | 2000-09-19 | American Home Products Corporation | Naphtho[2,3-B]heteroar-4-yl derivatives |
| US6147089A (en) * | 1998-09-17 | 2000-11-14 | Pfizer Inc. | Annulated 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines |
| GT199900147A (es) | 1998-09-17 | 1999-09-06 | 1, 2, 3, 4- tetrahidroquinolinas 2-sustituidas 4-amino sustituidas. | |
| US6350786B1 (en) | 1998-09-22 | 2002-02-26 | Hoffmann-La Roche Inc. | Stable complexes of poorly soluble compounds in ionic polymers |
| DE19845202A1 (de) | 1998-10-01 | 2000-04-06 | Wella Ag | Haarwuchsmittel |
| JP2002531515A (ja) | 1998-12-11 | 2002-09-24 | ファーマソリューションズ・インコーポレイテッド | 水に難溶性の薬剤のための自己乳化組成物 |
| EP1027885B1 (en) | 1999-02-09 | 2008-07-09 | Pfizer Products Inc. | Basic drug compositions with enhanced bioavailability |
| RU2238264C2 (ru) | 1999-02-24 | 2004-10-20 | Ф.Хоффманн-Ля Рош Аг | Производные бензола или пиридина и фармацевтическая композиция на их основе |
| HU228645B1 (en) | 1999-06-23 | 2013-04-29 | Syngenta Participations Ag | Method of producing nitroguanidine and nitroenamine derivatives |
| DE19930075A1 (de) | 1999-06-30 | 2001-01-04 | Bayer Ag | Neue Amino- und Amidosulfonamide als antivirale Mittel |
| US6451830B1 (en) | 1999-09-23 | 2002-09-17 | G.D. Searle & Co. | Use of substituted N,N-disubstituted non-fused heterocyclo amino compounds for inhibiting cholesteryl ester transfer protein activity |
| TWI269654B (en) | 1999-09-28 | 2007-01-01 | Baxter Healthcare Sa | N-substituted indole-3-glyoxylamide compounds having anti-tumor action |
| IL139941A0 (en) | 1999-12-02 | 2002-02-10 | Pfizer Prod Inc | Use of prostaglandin agonists to treat erectile dysfunction or impotence |
| WO2001045674A1 (en) | 1999-12-20 | 2001-06-28 | Cocensys, Inc. | Process for producing nanometer particles by fluid bed spray-drying |
| DE19962300A1 (de) | 1999-12-23 | 2001-06-28 | Asta Medica Ag | Substituierte N-Benzyl-Indol-3-yl-glyoxylsäure-Derivate mit Antitumorwirkung |
| US6306911B1 (en) | 2000-02-07 | 2001-10-23 | Ortho-Mcneil Pharmaceutical, Inc. | Substituted amino acids as neutral sphingomyelinase inhibitors |
| AU2001238424A1 (en) | 2000-02-18 | 2001-08-27 | Merck And Co., Inc. | Inhibitors of prenyl-protein transferase |
| WO2001060369A1 (en) | 2000-02-18 | 2001-08-23 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| DE10023484A1 (de) | 2000-05-09 | 2001-11-22 | Schering Ag | Anthranylamide und deren Verwendung als Arzneimittel |
| CN1224423C (zh) | 2000-07-17 | 2005-10-26 | 山之内制药株式会社 | 改善口服吸收的医药组合物 |
| US7115279B2 (en) | 2000-08-03 | 2006-10-03 | Curatolo William J | Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors |
| US6576644B2 (en) | 2000-09-06 | 2003-06-10 | Bristol-Myers Squibb Co. | Quinoline inhibitors of cGMP phosphodiesterase |
| WO2002022584A1 (en) | 2000-09-11 | 2002-03-21 | Merck & Co., Inc. | Thrombin inhibitors |
| US6642252B2 (en) | 2000-11-07 | 2003-11-04 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
| US7037528B2 (en) | 2000-12-22 | 2006-05-02 | Baxter International Inc. | Microprecipitation method for preparing submicron suspensions |
| ES2292830T3 (es) | 2001-02-21 | 2008-03-16 | Astrazeneca Ab | Compuestos heteropoliciclicos y su uso como antagonistas del receptor metabotropico de glutamato. |
| DE10110749A1 (de) | 2001-03-07 | 2002-09-12 | Bayer Ag | Substituierte Aminodicarbonsäurederivate |
| US7034013B2 (en) | 2001-03-20 | 2006-04-25 | Cydex, Inc. | Formulations containing propofol and a sulfoalkyl ether cyclodextrin |
| US7459470B2 (en) | 2001-05-08 | 2008-12-02 | Schering Ag | N-oxide anthranylamide derivatives and their use as medicaments |
| CZ20033341A3 (cs) | 2001-06-21 | 2004-10-13 | Pfizeráproductsáinc | Samoemulgující se kompozice inhibitorů přenosového proteinu cholesterylesteru |
| MXPA03011922A (es) | 2001-06-22 | 2004-03-26 | Pfizer Prod Inc | Composiciones farmaceuticas que contienen un dispersion solida de un farmaco ligeramente soluble en una matriz y plimero mejorador de solubilidad. |
| AU2002309172A1 (en) | 2001-06-22 | 2003-01-08 | Pfizer Products Inc. | Pharmaceutical compositions containing polymer and drug assemblies |
| EP1269994A3 (en) | 2001-06-22 | 2003-02-12 | Pfizer Products Inc. | Pharmaceutical compositions comprising drug and concentration-enhancing polymers |
| CA2448825C (en) | 2001-06-22 | 2009-08-11 | Pfizer Products Inc. | Pharmaceutical compositions of adsorbates of amorphous drug |
| WO2003030909A1 (en) | 2001-09-25 | 2003-04-17 | Bayer Pharmaceuticals Corporation | 2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer |
| US6713499B2 (en) | 2001-12-12 | 2004-03-30 | Hoffman-La Roche Inc. | 7-Amino-benzothiazole derivatives |
| EP1474144B1 (en) | 2002-02-01 | 2008-08-06 | Pfizer Products Inc. | Controlled release pharmaceutical dosage forms of a cholesteryl ester transfer protein inhibitor |
| AR038375A1 (es) | 2002-02-01 | 2005-01-12 | Pfizer Prod Inc | Composiciones farmaceuticas de inhibidores de la proteina de transferencia de esteres de colesterilo |
| GB0208280D0 (en) | 2002-04-10 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
| US7071210B2 (en) | 2002-07-02 | 2006-07-04 | Pfizer Inc. | CETP inhibitors in combination with antihypertensive agents and uses thereof |
| US20040053842A1 (en) | 2002-07-02 | 2004-03-18 | Pfizer Inc. | Methods of treatment with CETP inhibitors and antihypertensive agents |
| NZ532494A (en) | 2002-08-30 | 2006-03-31 | Japan Tobacco Inc | Dibenzylamine compound and medicinal use thereof |
| BR0317521A (pt) | 2002-12-20 | 2005-11-16 | Pfizer Prod Inc | Formas de dosagem compreendendo um inibidor da cetp e um inibidor da redutase hmg-coa |
| GB0303683D0 (en) | 2003-02-18 | 2003-03-19 | Prolysis Ltd | Antimicrobial agents |
| WO2004078128A2 (en) | 2003-02-28 | 2004-09-16 | Bayer Pharmaceuticals Corporation | Substituted pyridine derivatives useful in the treatment of cancer and other disorders |
| EP1601351A1 (en) | 2003-03-04 | 2005-12-07 | Pfizer Products Inc. | Use of ep2 selective receptor agonists in medical treatment |
| ATE383335T1 (de) | 2003-06-11 | 2008-01-15 | Lilly Co Eli | 3-amino-pyrrolidine als inhibitoren der monoamin- wiederaufnahme |
| RU2006102981A (ru) | 2003-08-04 | 2007-09-20 | Пфайзер Продактс Инк. (Us) | Лекарственные формы, обеспечивающие контролируемое высвобождение ингибиторов белка-переносчика эфиров холестерина и немедленное высвобождение ингибиторов hmg-соа-редуктазы |
| US7276610B2 (en) | 2003-08-27 | 2007-10-02 | Janssen Pharaceutica, Nv | Aryl piperidine amides |
| CN103330703A (zh) | 2003-09-26 | 2013-10-02 | 日本烟草产业株式会社 | 抑制残余脂蛋白产生的方法 |
| PT1732933E (pt) | 2004-03-26 | 2008-10-20 | Lilly Co Eli | Compostos para o tratamento da dislipidémia |
| TWI345568B (en) | 2004-04-02 | 2011-07-21 | Mitsubishi Tanabe Pharma Corp | Tetrahydronaphthyridine derivatives and a process for preparing the same |
| UA90269C2 (ru) | 2004-04-02 | 2010-04-26 | Мицубиси Танабе Фарма Корпорейшн | Тетрагидрохинолиновые производные и способ их получения |
| EP1737811B1 (en) | 2004-04-13 | 2016-08-10 | Merck Sharp & Dohme Corp. | Cetp inhibitors |
| PE20061124A1 (es) | 2004-11-23 | 2006-10-13 | Pfizer Prod Inc | Compuestos y derivados de dibencil amina |
| US8604055B2 (en) * | 2004-12-31 | 2013-12-10 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
| CN103102303B (zh) * | 2004-12-31 | 2015-10-28 | 雷迪博士实验室有限公司 | 作为cetp抑制剂的苄胺衍生物 |
| WO2006098394A1 (ja) * | 2005-03-14 | 2006-09-21 | Japan Tobacco Inc. | 脂質吸収抑制方法および脂質吸収抑制剤 |
| WO2006129167A1 (en) | 2005-05-31 | 2006-12-07 | Pfizer Products Inc. | PHARMACEUTICAL COMPOSITIONS OF CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITORS AND HMG-CoA REDUCTASE INHIBITORS |
| CN101448397B (zh) * | 2005-12-28 | 2013-04-24 | 雷迪博士实验室有限公司 | 选择性的苄胺衍生物和其作为胆固醇酯转运蛋白抑制剂的应用 |
| WO2007092642A2 (en) | 2006-02-09 | 2007-08-16 | Merck & Co., Inc. | Polymer formulations of cetp inhibitors |
| KR101172120B1 (ko) | 2006-05-10 | 2012-08-10 | 노파르티스 아게 | Ｃｅｔｐ 억제제로서의 바이시클릭 유도체 |
| US20100076021A1 (en) | 2006-11-15 | 2010-03-25 | Hidetomo Imase | Organic Compounds |
| US7790737B2 (en) | 2007-03-13 | 2010-09-07 | Kowa Company, Ltd. | Substituted pyrimidine compounds and their utility as CETP inhibitors |
| US9199967B2 (en) * | 2011-08-18 | 2015-12-01 | Dr. Reddy's Laboratories Ltd. | Substituted heterocyclic amine compounds as cholestryl ester-transfer protein (CETP) inhibitors |
-
2012
- 2012-08-17 US US14/238,272 patent/US9199967B2/en not_active Expired - Fee Related
- 2012-08-17 KR KR1020147005819A patent/KR101774223B1/ko not_active Expired - Fee Related
- 2012-08-17 WO PCT/IB2012/002056 patent/WO2013024358A2/en not_active Ceased
- 2012-08-17 CN CN201280045826.9A patent/CN103827105B/zh not_active Expired - Fee Related
- 2012-08-17 JP JP2014525513A patent/JP5964965B2/ja not_active Expired - Fee Related
- 2012-08-17 MX MX2014001849A patent/MX2014001849A/es unknown
- 2012-08-17 CA CA2845284A patent/CA2845284C/en not_active Expired - Fee Related
- 2012-08-17 EP EP12787075.6A patent/EP2744803A2/en not_active Withdrawn
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Also Published As
| Publication number | Publication date |
|---|---|
| CA2845284C (en) | 2018-03-06 |
| US20160045488A1 (en) | 2016-02-18 |
| KR20140050707A (ko) | 2014-04-29 |
| CN103827105A (zh) | 2014-05-28 |
| CA2845284A1 (en) | 2013-02-21 |
| JP2014525929A (ja) | 2014-10-02 |
| MX2014001849A (es) | 2014-10-24 |
| US9351969B2 (en) | 2016-05-31 |
| US9199967B2 (en) | 2015-12-01 |
| AU2012296262A8 (en) | 2016-10-20 |
| WO2013024358A3 (en) | 2013-07-11 |
| AU2012296262A1 (en) | 2014-04-03 |
| US20140256724A1 (en) | 2014-09-11 |
| EP2744803A2 (en) | 2014-06-25 |
| HK1197237A1 (en) | 2015-01-09 |
| CN103827105B (zh) | 2016-08-17 |
| WO2013024358A2 (en) | 2013-02-21 |
| KR101774223B1 (ko) | 2017-09-12 |
| AU2012296262B2 (en) | 2016-10-13 |
| NZ620914A (en) | 2016-02-26 |
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