JP2014525929A5 - - Google Patents

Info

Publication number

JP2014525929A5

JP2014525929A5 JP2014525513A JP2014525513A JP2014525929A5 JP 2014525929 A5 JP2014525929 A5 JP 2014525929A5 JP 2014525513 A JP2014525513 A JP 2014525513A JP 2014525513 A JP2014525513 A JP 2014525513A JP 2014525929 A5 JP2014525929 A5 JP 2014525929A5

Authority

JP

Japan

Prior art keywords

bis

composition

amino

methyl

cyclopropylmethyl

Prior art date

2012-08-17

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

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• 150000001875 compounds Chemical class 0.000 claims description 33
• 150000003839 salts Chemical class 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 22
• -1 cyano, hydroxyl Chemical group 0.000 claims description 17
• 125000003545 alkoxy group Chemical group 0.000 claims description 16
• 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 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 16
• 239000001257 hydrogen Substances 0.000 claims description 16
• 125000001188 haloalkyl group Chemical group 0.000 claims description 14
• 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 claims description 12
• 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 claims description 12
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 12
• 102000015779 HDL Lipoproteins Human genes 0.000 claims description 8
• 108010010234 HDL Lipoproteins Proteins 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 102000007330 LDL Lipoproteins Human genes 0.000 claims description 8
• 108010007622 LDL Lipoproteins Proteins 0.000 claims description 8
• 235000012000 cholesterol Nutrition 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 8
• 125000000623 heterocyclic group Chemical group 0.000 claims description 8
• 150000002431 hydrogen Chemical class 0.000 claims description 8
• 125000003118 aryl group Chemical group 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 3
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
• 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 2
• 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 2
• 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 2
• LYNAISSWYYGLMQ-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]methyl]-n,n-bis(cyclopropylmethyl)-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-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)CCC=3C=2)N(CC2CC2)CC2CC2)=N1 LYNAISSWYYGLMQ-UHFFFAOYSA-N 0.000 claims description 2
• HDVADQWWVUDSQP-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-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(C1=NN(C)N=N1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HDVADQWWVUDSQP-UHFFFAOYSA-N 0.000 claims description 2
• 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 claims description 2
• HTAKIGCTNNEKLV-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-propan-2-yltetrazol-5-yl)amino]methyl]-n,n-bis(cyclopropylmethyl)-7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-2-amine Chemical compound CC(C)N1N=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 HTAKIGCTNNEKLV-UHFFFAOYSA-N 0.000 claims description 2
• 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 2
• 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 2
• 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 2
• 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 2
• 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 claims description 2
• 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 2
• 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 2
• 125000002252 acyl group Chemical group 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
• QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 claims description 2
• 239000000203 mixture Substances 0.000 claims 32
• 239000003112 inhibitor Substances 0.000 claims 2
• 238000000034 method Methods 0.000 description 13
• 230000002401 inhibitory effect Effects 0.000 description 2
• WDELBDBJUHQMTA-UHFFFAOYSA-N O=C(Nc1ccc2)Oc1c2N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)Cc1c(N(CC2CC2)CC2CC2)nc(CCC2)c2c1 Chemical compound O=C(Nc1ccc2)Oc1c2N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)Cc1c(N(CC2CC2)CC2CC2)nc(CCC2)c2c1 WDELBDBJUHQMTA-UHFFFAOYSA-N 0.000 description 1
• 230000001268 conjugating effect Effects 0.000 description 1