JP2014524464A5 - - Google Patents
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- Publication number
- JP2014524464A5 JP2014524464A5 JP2014526594A JP2014526594A JP2014524464A5 JP 2014524464 A5 JP2014524464 A5 JP 2014524464A5 JP 2014526594 A JP2014526594 A JP 2014526594A JP 2014526594 A JP2014526594 A JP 2014526594A JP 2014524464 A5 JP2014524464 A5 JP 2014524464A5
- Authority
- JP
- Japan
- Prior art keywords
- oxo
- carboxamide
- tetrahydroisoquinoline
- pyrazol
- isobutyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- -1 4-isoxazolyl Chemical group 0.000 claims 81
- 229910052739 hydrogen Inorganic materials 0.000 claims 15
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 13
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 12
- 239000001257 hydrogen Substances 0.000 claims 11
- 239000008194 pharmaceutical composition Substances 0.000 claims 11
- 125000001153 fluoro group Chemical group F* 0.000 claims 10
- 150000002431 hydrogen Chemical class 0.000 claims 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 8
- 150000001875 compounds Chemical class 0.000 claims 8
- 125000003545 alkoxy group Chemical group 0.000 claims 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims 7
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 6
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 4
- 125000006684 polyhaloalkyl group Polymers 0.000 claims 4
- JICZMBWEYMJGOT-UHFFFAOYSA-N 1-oxo-3-(1h-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-n-[3-(trifluoromethoxy)phenyl]-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(F)(F)F)C(C2=CNN=C2)C1C(=O)NC1=CC=CC(OC(F)(F)F)=C1 JICZMBWEYMJGOT-UHFFFAOYSA-N 0.000 claims 3
- QNFCJQQDWXNWTO-UHFFFAOYSA-N 2-(2-methylpropyl)-1-oxo-3-(1h-pyrazol-4-yl)-n-[3-(trifluoromethoxy)phenyl]-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CNN=C2)C1C(=O)NC1=CC=CC(OC(F)(F)F)=C1 QNFCJQQDWXNWTO-UHFFFAOYSA-N 0.000 claims 3
- YUBRKYPPOSUWLM-UHFFFAOYSA-N 2-(2-methylpropyl)-1-oxo-3-pyridin-3-yl-n-[3-(trifluoromethoxy)phenyl]-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C=2C=NC=CC=2)C1C(=O)NC1=CC=CC(OC(F)(F)F)=C1 YUBRKYPPOSUWLM-UHFFFAOYSA-N 0.000 claims 3
- RRBGGBZMPKOJDM-UHFFFAOYSA-N 2-(2-methylpropyl)-3-(1-methylpyrazol-4-yl)-1-oxo-n-[3-(trifluoromethoxy)phenyl]-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CN(C)N=C2)C1C(=O)NC1=CC=CC(OC(F)(F)F)=C1 RRBGGBZMPKOJDM-UHFFFAOYSA-N 0.000 claims 3
- JSIBLKONNPMZEN-UHFFFAOYSA-N 3-(1-methylpyrazol-4-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-n-[3-(trifluoromethoxy)phenyl]-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=NN(C)C=C1C1N(CC(F)(F)F)C(=O)C2=CC=CC=C2C1C(=O)NC1=CC=CC(OC(F)(F)F)=C1 JSIBLKONNPMZEN-UHFFFAOYSA-N 0.000 claims 3
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims 3
- RUDMYTSUGCIHHF-UHFFFAOYSA-N C12=CC(F)=C(F)C=C2C(C(=O)N)CN(CC(F)(F)F)C1C=1C=NNC=1 Chemical compound C12=CC(F)=C(F)C=C2C(C(=O)N)CN(CC(F)(F)F)C1C=1C=NNC=1 RUDMYTSUGCIHHF-UHFFFAOYSA-N 0.000 claims 3
- 125000001246 bromo group Chemical group Br* 0.000 claims 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims 3
- 125000002346 iodo group Chemical group I* 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- DUJPTHOOGLZSBI-UHFFFAOYSA-N n-(3-chloro-5-cyanophenyl)-1-oxo-3-(1h-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(F)(F)F)C(C2=CNN=C2)C1C(=O)NC1=CC(Cl)=CC(C#N)=C1 DUJPTHOOGLZSBI-UHFFFAOYSA-N 0.000 claims 3
- WLFGHUIPZASVHI-UHFFFAOYSA-N n-(3-chloro-5-cyanophenyl)-2-(2-methylpropyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C=2C=NC=CC=2)C1C(=O)NC1=CC(Cl)=CC(C#N)=C1 WLFGHUIPZASVHI-UHFFFAOYSA-N 0.000 claims 3
- JHXCYMUYHAUQCG-UHFFFAOYSA-N n-(3-chloro-5-cyanophenyl)-2-(2-methylpropyl)-3-(1-methylpyrazol-4-yl)-1-oxo-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CN(C)N=C2)C1C(=O)NC1=CC(Cl)=CC(C#N)=C1 JHXCYMUYHAUQCG-UHFFFAOYSA-N 0.000 claims 3
- FWBCODRCMZEGNS-UHFFFAOYSA-N n-(3-chloro-5-cyanophenyl)-3-(1-methylpyrazol-4-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=NN(C)C=C1C1N(CC(F)(F)F)C(=O)C2=CC=CC=C2C1C(=O)NC1=CC(Cl)=CC(C#N)=C1 FWBCODRCMZEGNS-UHFFFAOYSA-N 0.000 claims 3
- ZKZZTOXSLJNDHR-UHFFFAOYSA-N n-(3-cyano-4-fluorophenyl)-1-oxo-3-(1h-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=C(C#N)C(F)=CC=C1NC(=O)C1C2=CC=CC=C2C(=O)N(CC(F)(F)F)C1C1=CNN=C1 ZKZZTOXSLJNDHR-UHFFFAOYSA-N 0.000 claims 3
- SFUWBVVLCRMYSF-UHFFFAOYSA-N n-(3-cyano-4-fluorophenyl)-2-(2-methylpropyl)-1-oxo-3-(1,2-thiazol-4-yl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CSN=C2)C1C(=O)NC1=CC=C(F)C(C#N)=C1 SFUWBVVLCRMYSF-UHFFFAOYSA-N 0.000 claims 3
- DNKSHWRXGBIWBR-UHFFFAOYSA-N n-(3-cyano-4-fluorophenyl)-2-(2-methylpropyl)-1-oxo-3-(1h-pyrazol-4-yl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CNN=C2)C1C(=O)NC1=CC=C(F)C(C#N)=C1 DNKSHWRXGBIWBR-UHFFFAOYSA-N 0.000 claims 3
- KRXCWKMUHKEUAC-UHFFFAOYSA-N n-(3-cyano-4-fluorophenyl)-2-(2-methylpropyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C=2C=NC=CC=2)C1C(=O)NC1=CC=C(F)C(C#N)=C1 KRXCWKMUHKEUAC-UHFFFAOYSA-N 0.000 claims 3
- IECIUAKUBYSJAC-UHFFFAOYSA-N n-(3-cyano-4-fluorophenyl)-2-(2-methylpropyl)-1-oxo-3-pyrimidin-5-yl-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C=2C=NC=NC=2)C1C(=O)NC1=CC=C(F)C(C#N)=C1 IECIUAKUBYSJAC-UHFFFAOYSA-N 0.000 claims 3
- UQEVFULMKDMOKC-UHFFFAOYSA-N n-(3-cyano-4-fluorophenyl)-2-(cyclopropylmethyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=C(C#N)C(F)=CC=C1NC(=O)C1C2=CC=CC=C2C(=O)N(CC2CC2)C1C1=CC=CN=C1 UQEVFULMKDMOKC-UHFFFAOYSA-N 0.000 claims 3
- WIRJSBWWORVKOE-UHFFFAOYSA-N n-(3-cyano-4-fluorophenyl)-3-(1-methylpyrazol-4-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=NN(C)C=C1C1N(CC(F)(F)F)C(=O)C2=CC=CC=C2C1C(=O)NC1=CC=C(F)C(C#N)=C1 WIRJSBWWORVKOE-UHFFFAOYSA-N 0.000 claims 3
- OOBPRDMRPKYXJS-UHFFFAOYSA-N n-(3-cyano-4-fluorophenyl)-7-methoxy-2-(2-methylpropyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxamide Chemical compound CC(C)CN1C(=O)C2=CC(OC)=CC=C2C(C(=O)NC=2C=C(C(F)=CC=2)C#N)C1C1=CC=CN=C1 OOBPRDMRPKYXJS-UHFFFAOYSA-N 0.000 claims 3
- MTYRHOGVFUQJMO-UHFFFAOYSA-N n-(3-cyano-5-fluorophenyl)-1-oxo-3-(1h-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound N#CC1=CC(F)=CC(NC(=O)C2C3=CC=CC=C3C(=O)N(CC(F)(F)F)C2C2=CNN=C2)=C1 MTYRHOGVFUQJMO-UHFFFAOYSA-N 0.000 claims 3
- NZKLVVKLAPDEFK-UHFFFAOYSA-N n-(3-cyano-5-fluorophenyl)-2-(2-methylpropyl)-1-oxo-3-(1h-pyrazol-4-yl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CNN=C2)C1C(=O)NC1=CC(F)=CC(C#N)=C1 NZKLVVKLAPDEFK-UHFFFAOYSA-N 0.000 claims 3
- UHTKJDSQXCHBPW-UHFFFAOYSA-N n-(3-cyano-5-fluorophenyl)-2-(2-methylpropyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C=2C=NC=CC=2)C1C(=O)NC1=CC(F)=CC(C#N)=C1 UHTKJDSQXCHBPW-UHFFFAOYSA-N 0.000 claims 3
- SVQSZWWFPXNZKY-UHFFFAOYSA-N n-(3-cyano-5-fluorophenyl)-2-(2-methylpropyl)-3-(1-methylpyrazol-4-yl)-1-oxo-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CN(C)N=C2)C1C(=O)NC1=CC(F)=CC(C#N)=C1 SVQSZWWFPXNZKY-UHFFFAOYSA-N 0.000 claims 3
- WSNLIJDISCITEW-UHFFFAOYSA-N n-(3-cyano-5-fluorophenyl)-7-fluoro-3-(1-methylpyrazol-4-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=NN(C)C=C1C1N(CC(F)(F)F)C(=O)C2=CC(F)=CC=C2C1C(=O)NC1=CC(F)=CC(C#N)=C1 WSNLIJDISCITEW-UHFFFAOYSA-N 0.000 claims 3
- WVKDLOUBIUKWEP-UHFFFAOYSA-N n-(3-cyanophenyl)-1-oxo-3-(1h-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(F)(F)F)C(C2=CNN=C2)C1C(=O)NC1=CC=CC(C#N)=C1 WVKDLOUBIUKWEP-UHFFFAOYSA-N 0.000 claims 3
- XWJINLLYMWHJSS-UHFFFAOYSA-N n-(3-cyanophenyl)-1-oxo-3-pyridin-3-yl-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(F)(F)F)C(C=2C=NC=CC=2)C1C(=O)NC1=CC=CC(C#N)=C1 XWJINLLYMWHJSS-UHFFFAOYSA-N 0.000 claims 3
- HBHDRUSNUINJCC-UHFFFAOYSA-N n-(3-cyanophenyl)-2-(2-methylpropyl)-1-oxo-3-(1h-pyrazol-4-yl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CNN=C2)C1C(=O)NC1=CC=CC(C#N)=C1 HBHDRUSNUINJCC-UHFFFAOYSA-N 0.000 claims 3
- OQSRKNUAEQWIET-UHFFFAOYSA-N n-(3-cyanophenyl)-2-(2-methylpropyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C=2C=NC=CC=2)C1C(=O)NC1=CC=CC(C#N)=C1 OQSRKNUAEQWIET-UHFFFAOYSA-N 0.000 claims 3
- LQICCRRRLHPGDM-UHFFFAOYSA-N n-(3-cyanophenyl)-2-(2-methylpropyl)-3-(1-methylpyrazol-4-yl)-1-oxo-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CN(C)N=C2)C1C(=O)NC1=CC=CC(C#N)=C1 LQICCRRRLHPGDM-UHFFFAOYSA-N 0.000 claims 3
- HWPBLGMXZFBSRA-UHFFFAOYSA-N n-(3-cyanophenyl)-3-(1-methylpyrazol-4-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=NN(C)C=C1C1N(CC(F)(F)F)C(=O)C2=CC=CC=C2C1C(=O)NC1=CC=CC(C#N)=C1 HWPBLGMXZFBSRA-UHFFFAOYSA-N 0.000 claims 3
- YSCJKBTWYQOCGY-UHFFFAOYSA-N n-(3-cyanophenyl)-6-fluoro-2-(2-methylpropyl)-3-(1-methylpyrazol-4-yl)-1-oxo-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC(F)=CC=C2C(=O)N(CC(C)C)C(C2=CN(C)N=C2)C1C(=O)NC1=CC=CC(C#N)=C1 YSCJKBTWYQOCGY-UHFFFAOYSA-N 0.000 claims 3
- CLGVELMOYDGOFY-UHFFFAOYSA-N n-[3-fluoro-5-(trifluoromethoxy)phenyl]-1-oxo-3-(1h-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound FC(F)(F)OC1=CC(F)=CC(NC(=O)C2C3=CC=CC=C3C(=O)N(CC(F)(F)F)C2C2=CNN=C2)=C1 CLGVELMOYDGOFY-UHFFFAOYSA-N 0.000 claims 3
- JSSSNBFUTZJGKA-UHFFFAOYSA-N n-[3-fluoro-5-(trifluoromethoxy)phenyl]-1-oxo-3-pyridin-3-yl-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound FC(F)(F)OC1=CC(F)=CC(NC(=O)C2C3=CC=CC=C3C(=O)N(CC(F)(F)F)C2C=2C=NC=CC=2)=C1 JSSSNBFUTZJGKA-UHFFFAOYSA-N 0.000 claims 3
- GYGJAMIGQBAHKB-UHFFFAOYSA-N n-[3-fluoro-5-(trifluoromethoxy)phenyl]-2-(2-methylpropyl)-1-oxo-3-(1h-pyrazol-4-yl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CNN=C2)C1C(=O)NC1=CC(F)=CC(OC(F)(F)F)=C1 GYGJAMIGQBAHKB-UHFFFAOYSA-N 0.000 claims 3
- YMMYZVALPCGYPU-UHFFFAOYSA-N n-[3-fluoro-5-(trifluoromethoxy)phenyl]-2-(2-methylpropyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C=2C=NC=CC=2)C1C(=O)NC1=CC(F)=CC(OC(F)(F)F)=C1 YMMYZVALPCGYPU-UHFFFAOYSA-N 0.000 claims 3
- JJHLIXZXBNUQML-UHFFFAOYSA-N n-[3-fluoro-5-(trifluoromethoxy)phenyl]-3-(1-methylpyrazol-4-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=NN(C)C=C1C1N(CC(F)(F)F)C(=O)C2=CC=CC=C2C1C(=O)NC1=CC(F)=CC(OC(F)(F)F)=C1 JJHLIXZXBNUQML-UHFFFAOYSA-N 0.000 claims 3
- RLFXBAYIHTZALY-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethoxy)phenyl]-1-oxo-3-(1h-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=C(OC(F)(F)F)C(F)=CC=C1NC(=O)C1C2=CC=CC=C2C(=O)N(CC(F)(F)F)C1C1=CNN=C1 RLFXBAYIHTZALY-UHFFFAOYSA-N 0.000 claims 3
- IKWRACQACAOENU-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethoxy)phenyl]-1-oxo-3-pyridin-3-yl-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=C(OC(F)(F)F)C(F)=CC=C1NC(=O)C1C2=CC=CC=C2C(=O)N(CC(F)(F)F)C1C1=CC=CN=C1 IKWRACQACAOENU-UHFFFAOYSA-N 0.000 claims 3
- WEBUSKBEDKNZDO-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethoxy)phenyl]-2-(2-methylpropyl)-1-oxo-3-(1h-pyrazol-4-yl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CNN=C2)C1C(=O)NC1=CC=C(F)C(OC(F)(F)F)=C1 WEBUSKBEDKNZDO-UHFFFAOYSA-N 0.000 claims 3
- VDHYXQOSBKVCPK-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethoxy)phenyl]-2-(2-methylpropyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C=2C=NC=CC=2)C1C(=O)NC1=CC=C(F)C(OC(F)(F)F)=C1 VDHYXQOSBKVCPK-UHFFFAOYSA-N 0.000 claims 3
- MCXVJAKEYWVFBT-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethoxy)phenyl]-3-(1-methylpyrazol-4-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=NN(C)C=C1C1N(CC(F)(F)F)C(=O)C2=CC=CC=C2C1C(=O)NC1=CC=C(F)C(OC(F)(F)F)=C1 MCXVJAKEYWVFBT-UHFFFAOYSA-N 0.000 claims 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 3
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims 3
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 239000012453 solvate Substances 0.000 claims 3
- YQYMNJMKTNOYQY-UHFFFAOYSA-N 2-butyl-n-(3-cyano-4-fluorophenyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CCCC)C(C=2C=NC=CC=2)C1C(=O)NC1=CC=C(F)C(C#N)=C1 YQYMNJMKTNOYQY-UHFFFAOYSA-N 0.000 claims 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- UJHYREHWQZFQPP-UHFFFAOYSA-N n-(3-chloro-5-cyanophenyl)-2-(2-methylpropyl)-1-oxo-3-(1h-pyrazol-4-yl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CNN=C2)C1C(=O)NC1=CC(Cl)=CC(C#N)=C1 UJHYREHWQZFQPP-UHFFFAOYSA-N 0.000 claims 2
- OWFHJWPIIYKLQN-UHFFFAOYSA-N n-(3-cyano-5-fluorophenyl)-3-(1-methylpyrazol-4-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C1=NN(C)C=C1C1N(CC(F)(F)F)C(=O)C2=CC=CC=C2C1C(=O)NC1=CC(F)=CC(C#N)=C1 OWFHJWPIIYKLQN-UHFFFAOYSA-N 0.000 claims 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000001544 thienyl group Chemical group 0.000 claims 2
- LASDGSRKRVGQHF-UHFFFAOYSA-N 1-oxo-3-(1h-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound FC(F)(F)CN1C(=O)C2=CC=CC=C2C(C(=O)O)C1C=1C=NNC=1 LASDGSRKRVGQHF-UHFFFAOYSA-N 0.000 claims 1
- PBUPDIAWZXEDNZ-UHFFFAOYSA-N 1-oxo-3-pyridin-3-yl-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound FC(F)(F)CN1C(=O)C2=CC=CC=C2C(C(=O)O)C1C1=CC=CN=C1 PBUPDIAWZXEDNZ-UHFFFAOYSA-N 0.000 claims 1
- SQPWTJARNUDHMP-UHFFFAOYSA-N 2-(2-methylpropyl)-1-oxo-3-(1,2-thiazol-4-yl)-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound OC(=O)C1C2=CC=CC=C2C(=O)N(CC(C)C)C1C=1C=NSC=1 SQPWTJARNUDHMP-UHFFFAOYSA-N 0.000 claims 1
- WMAVMURGRAZKPX-UHFFFAOYSA-N 2-(2-methylpropyl)-1-oxo-3-(1h-pyrazol-4-yl)-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound OC(=O)C1C2=CC=CC=C2C(=O)N(CC(C)C)C1C=1C=NNC=1 WMAVMURGRAZKPX-UHFFFAOYSA-N 0.000 claims 1
- XMBLQXVXXZWAGQ-UHFFFAOYSA-N 2-(2-methylpropyl)-1-oxo-3-pyrimidin-5-yl-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound OC(=O)C1C2=CC=CC=C2C(=O)N(CC(C)C)C1C1=CN=CN=C1 XMBLQXVXXZWAGQ-UHFFFAOYSA-N 0.000 claims 1
- IWWLLORJWHZGTG-UHFFFAOYSA-N 2-(2-methylpropyl)-3-(1-methylpyrazol-4-yl)-1-oxo-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound OC(=O)C1C2=CC=CC=C2C(=O)N(CC(C)C)C1C=1C=NN(C)C=1 IWWLLORJWHZGTG-UHFFFAOYSA-N 0.000 claims 1
- YRYFQHJZGVZJJN-UHFFFAOYSA-N 2-(cyclopropylmethyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound O=C1C2=CC=CC=C2C(C(=O)O)C(C=2C=NC=CC=2)N1CC1CC1 YRYFQHJZGVZJJN-UHFFFAOYSA-N 0.000 claims 1
- FYPYNKLSWXBORO-UHFFFAOYSA-N 2-butyl-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound OC(=O)C1C2=CC=CC=C2C(=O)N(CCCC)C1C1=CC=CN=C1 FYPYNKLSWXBORO-UHFFFAOYSA-N 0.000 claims 1
- XKDCNBVUKLCLQV-UHFFFAOYSA-N 2-butyl-3-(5-cyanothiophen-2-yl)-1-oxo-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound OC(=O)C1C2=CC=CC=C2C(=O)N(CCCC)C1C1=CC=C(C#N)S1 XKDCNBVUKLCLQV-UHFFFAOYSA-N 0.000 claims 1
- QIPGPXDSVFNYHP-UHFFFAOYSA-N 2-butyl-n-(3-cyano-4-fluorophenyl)-3-(5-cyanothiophen-2-yl)-1-oxo-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CCCC)C(C=2SC(=CC=2)C#N)C1C(=O)NC1=CC=C(F)C(C#N)=C1 QIPGPXDSVFNYHP-UHFFFAOYSA-N 0.000 claims 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- JTQUUBROCKVJAP-UHFFFAOYSA-N 3-(1-methylpyrazol-4-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound C1=NN(C)C=C1C1N(CC(F)(F)F)C(=O)C2=CC=CC=C2C1C(O)=O JTQUUBROCKVJAP-UHFFFAOYSA-N 0.000 claims 1
- RLSAMBQRYZGJCC-UHFFFAOYSA-N 3-(5-cyanothiophen-2-yl)-2-(cyclopropylmethyl)-1-oxo-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound O=C1C2=CC=CC=C2C(C(=O)O)C(C=2SC(=CC=2)C#N)N1CC1CC1 RLSAMBQRYZGJCC-UHFFFAOYSA-N 0.000 claims 1
- KQQPSPJCZUMHQT-UHFFFAOYSA-N 3-(5-cyanothiophen-2-yl)-6-fluoro-2-(2-methylpropyl)-1-oxo-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound OC(=O)C1C2=CC(F)=CC=C2C(=O)N(CC(C)C)C1C1=CC=C(C#N)S1 KQQPSPJCZUMHQT-UHFFFAOYSA-N 0.000 claims 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- MDYLZMIVGWRIOD-UHFFFAOYSA-N 6-fluoro-2-(2-methylpropyl)-3-(1-methylpyrazol-4-yl)-1-oxo-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound OC(=O)C1C2=CC(F)=CC=C2C(=O)N(CC(C)C)C1C=1C=NN(C)C=1 MDYLZMIVGWRIOD-UHFFFAOYSA-N 0.000 claims 1
- QVVCPOWOEQAEEU-UHFFFAOYSA-N 7-fluoro-2-(2-methylpropyl)-3-(1-methylpyrazol-4-yl)-1-oxo-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound OC(=O)C1C2=CC=C(F)C=C2C(=O)N(CC(C)C)C1C=1C=NN(C)C=1 QVVCPOWOEQAEEU-UHFFFAOYSA-N 0.000 claims 1
- GBDFOFDXSIDEBM-UHFFFAOYSA-N 7-methoxy-2-(2-methylpropyl)-1-oxo-3-pyridin-3-yl-3,4-dihydroisoquinoline-4-carboxylic acid Chemical compound CC(C)CN1C(=O)C2=CC(OC)=CC=C2C(C(O)=O)C1C1=CC=CN=C1 GBDFOFDXSIDEBM-UHFFFAOYSA-N 0.000 claims 1
- MKVRJAKPQCTKTJ-UHFFFAOYSA-N CC(C)CN(C(C(C(N)=O)C1=CC=CC=C11)(C2=CN(C)N=C2)C(C=C2)=CC(C#N)=C2F)C1=O Chemical compound CC(C)CN(C(C(C(N)=O)C1=CC=CC=C11)(C2=CN(C)N=C2)C(C=C2)=CC(C#N)=C2F)C1=O MKVRJAKPQCTKTJ-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 239000003430 antimalarial agent Substances 0.000 claims 1
- 150000004982 aromatic amines Chemical class 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 201000004792 malaria Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 1
- SUINKIIVSSUICN-UHFFFAOYSA-N n-(3-cyano-4-fluorophenyl)-2-(2-methylpropyl)-3-(1-methylpyrazol-4-yl)-1-oxo-3,4-dihydroisoquinoline-4-carboxamide Chemical compound C12=CC=CC=C2C(=O)N(CC(C)C)C(C2=CN(C)N=C2)C1C(=O)NC1=CC=C(F)C(C#N)=C1 SUINKIIVSSUICN-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
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| US201161527594P | 2011-08-25 | 2011-08-25 | |
| US61/527,594 | 2011-08-25 | ||
| PCT/IB2012/054305 WO2013027196A1 (en) | 2011-08-25 | 2012-08-24 | Substituted 2-alkyl-1-oxo-n-phenyl-3-heteroaryl-1,2,3,4- tetrahydroisoquinoline-4-carboxamides for antimalarial therapies |
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| JP2014524464A JP2014524464A (ja) | 2014-09-22 |
| JP2014524464A5 true JP2014524464A5 (enExample) | 2015-09-03 |
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|---|---|---|---|---|
| CN111886225A (zh) * | 2017-08-21 | 2020-11-03 | 纳维根公司 | Arf6抑制剂及相关方法 |
| EP3892332A1 (en) | 2020-04-09 | 2021-10-13 | University Of Kentucky Research Foundation | New anti-malarial agents |
| CA3214899A1 (en) | 2021-04-15 | 2022-10-20 | Lutz Weber | Isoquinoline derivatives for use as antiviral and antitumour agents |
| EP4074314A1 (en) | 2021-04-15 | 2022-10-19 | Valdospan GmbH | Isoquinoline derivatives for use as antiviral and antitumour agents |
| AU2023363824A1 (en) | 2022-10-17 | 2025-04-17 | Rdp Pharma Ag | Isoquinoline derivatives as protein degraders, e7 degraders, antivirals, tumor therapeutics and immune suppressives |
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| US5409938A (en) * | 1994-02-14 | 1995-04-25 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Antimalarial korupensamines and pharmaceutical compositions and medical uses thereof |
| US5639761A (en) * | 1994-02-14 | 1997-06-17 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Antimalarial naphthylisoquinoline alkaloids and pharmaceutical compositions and medical uses thereof |
| US6921762B2 (en) * | 2001-11-16 | 2005-07-26 | Amgen Inc. | Substituted indolizine-like compounds and methods of use |
| WO2004004727A1 (en) | 2002-07-03 | 2004-01-15 | Axys Pharmaceuticals, Inc. | 3,4-dihydroisoquinolin-1-one derivatives as inducers of apoptosis |
| DE10237722A1 (de) * | 2002-08-17 | 2004-08-19 | Aventis Pharma Deutschland Gmbh | Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase |
| DE10312963A1 (de) | 2003-03-24 | 2004-10-07 | Aventis Pharma Deutschland Gmbh | Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament |
| UY29440A1 (es) * | 2005-03-25 | 2006-10-02 | Glaxo Group Ltd | Nuevos compuestos |
| RU2302417C1 (ru) * | 2006-03-14 | 2007-07-10 | Иващенко Андрей Александрович | 1-оксо-3-(1н-индол-3-ил)-1,2,3,4-тетрагидроизохинолины, способы их получения, комбинаторная библиотека и фокусированная библиотека |
| BRPI0912871A2 (pt) * | 2008-05-19 | 2015-10-20 | Actelion Pharmaceuticals Ltd | novas tetraidroisoquinolinas como agentes antimaláricos. |
| GB0820856D0 (en) | 2008-11-14 | 2008-12-24 | Univ Leuven Kath | Novel inhibitors of flavivirus replication |
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2012
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