CA2779989A1 - Quinazoline compounds - Google Patents
Quinazoline compounds Download PDFInfo
- Publication number
- CA2779989A1 CA2779989A1 CA2779989A CA2779989A CA2779989A1 CA 2779989 A1 CA2779989 A1 CA 2779989A1 CA 2779989 A CA2779989 A CA 2779989A CA 2779989 A CA2779989 A CA 2779989A CA 2779989 A1 CA2779989 A1 CA 2779989A1
- Authority
- CA
- Canada
- Prior art keywords
- amino
- methyl
- quinazolinyl
- methyloxy
- alkyl
- 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.)
- Abandoned
Links
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title description 80
- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- 238000000034 method Methods 0.000 claims abstract description 46
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 230
- -1 nitro, amino Chemical group 0.000 claims description 172
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 77
- 229910052736 halogen Inorganic materials 0.000 claims description 59
- 150000002367 halogens Chemical class 0.000 claims description 59
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 229910052717 sulfur Chemical group 0.000 claims description 31
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
- 125000005842 heteroatom Chemical group 0.000 claims description 28
- 206010019280 Heart failures Diseases 0.000 claims description 27
- 125000003282 alkyl amino group Chemical group 0.000 claims description 25
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 22
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 125000003386 piperidinyl group Chemical group 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 16
- 125000002757 morpholinyl group Chemical group 0.000 claims description 16
- 239000001301 oxygen Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 14
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 239000011593 sulfur Chemical group 0.000 claims description 13
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 12
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 12
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 12
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 11
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 11
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 10
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims description 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 8
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 7
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 7
- 101000662993 Homo sapiens Serine/threonine-protein kinase TNNI3K Proteins 0.000 claims description 7
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 7
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 5
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 5
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- OQHRVARQAYXXKB-UHFFFAOYSA-N 3-[(6-aminoquinazolin-4-yl)amino]-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC(N)=CC=C3N=CN=2)=C1 OQHRVARQAYXXKB-UHFFFAOYSA-N 0.000 claims description 5
- 102100037670 Serine/threonine-protein kinase TNNI3K Human genes 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000006771 (C1-C6) haloalkylthio group Chemical group 0.000 claims description 4
- 125000006648 (C1-C8) haloalkyl group Chemical group 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- IAWACGQFSRGVHG-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-methylsulfanylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(SC)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 IAWACGQFSRGVHG-UHFFFAOYSA-N 0.000 claims description 3
- YUSROMRPOFFTMX-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 YUSROMRPOFFTMX-UHFFFAOYSA-N 0.000 claims description 3
- PNEYRCXCZRJLTK-UHFFFAOYSA-N 3-[(6-methoxy-7-propan-2-yloxyquinazolin-4-yl)amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC(OC)=C(OC(C)C)C=C3N=CN=2)=C1 PNEYRCXCZRJLTK-UHFFFAOYSA-N 0.000 claims description 3
- TUINBAPNAKPWHO-UHFFFAOYSA-N 3-[[7-(3-methoxypropoxy)quinazolin-4-yl]amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC=C(OCCCOC)C=C3N=CN=2)=C1 TUINBAPNAKPWHO-UHFFFAOYSA-N 0.000 claims description 3
- XBOGVIDEPXMHTN-UHFFFAOYSA-N 4-(dimethylamino)-3-[[6-(dimethylamino)quinazolin-4-yl]amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC(=CC=C3N=CN=2)N(C)C)=C1 XBOGVIDEPXMHTN-UHFFFAOYSA-N 0.000 claims description 3
- HSXXPAFGNVISQH-UHFFFAOYSA-N 4-(dimethylamino)-n-methyl-3-[[6-(methylamino)quinazolin-4-yl]amino]benzenesulfonamide Chemical compound C12=CC(NC)=CC=C2N=CN=C1NC1=CC(S(=O)(=O)NC)=CC=C1N(C)C HSXXPAFGNVISQH-UHFFFAOYSA-N 0.000 claims description 3
- YIHUHJGDULXMLF-UHFFFAOYSA-N 2-fluoro-n-methyl-4-(2,2,2-trifluoroethoxy)-5-[(5,6,7-trimethoxyquinazolin-4-yl)amino]benzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)NC)=CC(NC=2C3=C(OC)C(OC)=C(OC)C=C3N=CN=2)=C1OCC(F)(F)F YIHUHJGDULXMLF-UHFFFAOYSA-N 0.000 claims description 2
- JHLYWKKKYYQEPH-UHFFFAOYSA-N 3-(7,8-dihydro-[1,4]dioxino[2,3-g]quinazolin-4-ylamino)-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC=4OCCOC=4C=C3N=CN=2)=C1 JHLYWKKKYYQEPH-UHFFFAOYSA-N 0.000 claims description 2
- KFBXNJYHMZCVDH-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 KFBXNJYHMZCVDH-UHFFFAOYSA-N 0.000 claims description 2
- RJSKVBNUBJSMHI-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-4-fluoro-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(F)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 RJSKVBNUBJSMHI-UHFFFAOYSA-N 0.000 claims description 2
- DUKKDKHUSSZCIU-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-4-methoxy-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 DUKKDKHUSSZCIU-UHFFFAOYSA-N 0.000 claims description 2
- CUEQUMNPZOWSNT-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-[methyl(2,2,2-trifluoroethyl)amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)CC(F)(F)F)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 CUEQUMNPZOWSNT-UHFFFAOYSA-N 0.000 claims description 2
- YZXJNXXOESJUDW-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-methylsulfonylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(S(C)(=O)=O)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 YZXJNXXOESJUDW-UHFFFAOYSA-N 0.000 claims description 2
- OBQJMFWNEPIQKM-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-morpholin-4-ylbenzenesulfonamide Chemical compound N=1C=NC2=CC(OC)=CC(OC)=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1CCOCC1 OBQJMFWNEPIQKM-UHFFFAOYSA-N 0.000 claims description 2
- DNRQPIJNEGGAAA-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 DNRQPIJNEGGAAA-UHFFFAOYSA-N 0.000 claims description 2
- WSNMNKYBSOWHFZ-UHFFFAOYSA-N 3-[(5-chloro-6,7-dimethoxyquinazolin-4-yl)amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC(NC=2C3=C(Cl)C(OC)=C(OC)C=C3N=CN=2)=C1 WSNMNKYBSOWHFZ-UHFFFAOYSA-N 0.000 claims description 2
- OBHNJQYLPQMMJS-UHFFFAOYSA-N 3-[(5-ethoxy-7-methoxyquinazolin-4-yl)amino]-n-methyl-4-(1,1,1-trifluoropropan-2-yloxy)benzenesulfonamide Chemical compound C=12C(OCC)=CC(OC)=CC2=NC=NC=1NC1=CC(S(=O)(=O)NC)=CC=C1OC(C)C(F)(F)F OBHNJQYLPQMMJS-UHFFFAOYSA-N 0.000 claims description 2
- SLWXWVRNVKDGNM-UHFFFAOYSA-N 3-[(5-ethoxy-7-methoxyquinazolin-4-yl)amino]-n-methyl-4-(trifluoromethoxy)benzenesulfonamide Chemical compound C=12C(OCC)=CC(OC)=CC2=NC=NC=1NC1=CC(S(=O)(=O)NC)=CC=C1OC(F)(F)F SLWXWVRNVKDGNM-UHFFFAOYSA-N 0.000 claims description 2
- OLSJRINRIBWJFA-UHFFFAOYSA-N 3-[(6,7-diethoxyquinazolin-4-yl)amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=NC=1NC1=CC(S(=O)(=O)NC)=CC=C1OCC(F)(F)F OLSJRINRIBWJFA-UHFFFAOYSA-N 0.000 claims description 2
- MVOYMLQGDVPZJA-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-4-[ethyl(methyl)amino]-n-methylbenzenesulfonamide Chemical compound CCN(C)C1=CC=C(S(=O)(=O)NC)C=C1NC1=NC=NC2=CC(OC)=C(OC)C=C12 MVOYMLQGDVPZJA-UHFFFAOYSA-N 0.000 claims description 2
- TUSITRBRNZHFMX-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-4-methoxy-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 TUSITRBRNZHFMX-UHFFFAOYSA-N 0.000 claims description 2
- JQQPJAQDAUBSJJ-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-(1,1,1-trifluoropropan-2-yloxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(C)C(F)(F)F)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 JQQPJAQDAUBSJJ-UHFFFAOYSA-N 0.000 claims description 2
- QWUCNVDERBNALL-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-(2,2,2-trifluoroethylsulfanyl)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(SCC(F)(F)F)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 QWUCNVDERBNALL-UHFFFAOYSA-N 0.000 claims description 2
- KYOYDUMRZOHKKQ-HXUWFJFHSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-[(2r)-2-(trifluoromethyl)pyrrolidin-1-yl]benzenesulfonamide Chemical compound N=1C=NC2=CC(OC)=C(OC)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1CCC[C@@H]1C(F)(F)F KYOYDUMRZOHKKQ-HXUWFJFHSA-N 0.000 claims description 2
- FHMGNHOMVMUVSO-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-[methyl(2,2,2-trifluoroethyl)amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)CC(F)(F)F)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 FHMGNHOMVMUVSO-UHFFFAOYSA-N 0.000 claims description 2
- DMNHYDHDZWJZMB-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-methylsulfanylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(SC)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 DMNHYDHDZWJZMB-UHFFFAOYSA-N 0.000 claims description 2
- LMHKYZSAOCJQOU-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-methylsulfonylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(S(C)(=O)=O)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 LMHKYZSAOCJQOU-UHFFFAOYSA-N 0.000 claims description 2
- LNRBCVJBFACPLQ-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-morpholin-4-ylbenzenesulfonamide Chemical compound N=1C=NC2=CC(OC)=C(OC)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1CCOCC1 LNRBCVJBFACPLQ-UHFFFAOYSA-N 0.000 claims description 2
- PAZABHJZVINCPU-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-piperidin-1-ylbenzenesulfonamide Chemical compound N=1C=NC2=CC(OC)=C(OC)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1CCCCC1 PAZABHJZVINCPU-UHFFFAOYSA-N 0.000 claims description 2
- CZTAUKHLISFCPJ-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-propan-2-yloxybenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(C)C)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 CZTAUKHLISFCPJ-UHFFFAOYSA-N 0.000 claims description 2
- HJWJQWGYZYLMGV-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 HJWJQWGYZYLMGV-UHFFFAOYSA-N 0.000 claims description 2
- BWUYSVPJNQGHBZ-GOSISDBHSA-N 3-[(6-chloroquinazolin-4-yl)amino]-n-methyl-4-[(2r)-2-(trifluoromethyl)pyrrolidin-1-yl]benzenesulfonamide Chemical compound N=1C=NC2=CC=C(Cl)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1CCC[C@@H]1C(F)(F)F BWUYSVPJNQGHBZ-GOSISDBHSA-N 0.000 claims description 2
- WNFCKMNVCNNTHE-UHFFFAOYSA-N 3-[(6-chloroquinazolin-4-yl)amino]-n-methyl-4-piperidin-1-ylbenzenesulfonamide Chemical compound N=1C=NC2=CC=C(Cl)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1CCCCC1 WNFCKMNVCNNTHE-UHFFFAOYSA-N 0.000 claims description 2
- NZGQZHSAVLWQJD-UHFFFAOYSA-N 3-[(6-iodo-7-methoxyquinazolin-4-yl)amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC(I)=C(OC)C=C3N=CN=2)=C1 NZGQZHSAVLWQJD-UHFFFAOYSA-N 0.000 claims description 2
- LVRXFIZRHGNOHR-UHFFFAOYSA-N 3-[(7-aminoquinazolin-4-yl)amino]-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC=C(N)C=C3N=CN=2)=C1 LVRXFIZRHGNOHR-UHFFFAOYSA-N 0.000 claims description 2
- SWLMPOQQJCLDHU-UHFFFAOYSA-N 3-[(7-hydroxy-6-methoxyquinazolin-4-yl)amino]-N-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC(OC)=C(O)C=C3N=CN=2)=C1 SWLMPOQQJCLDHU-UHFFFAOYSA-N 0.000 claims description 2
- POKHOZHYJRLTBV-UHFFFAOYSA-N 3-[(7-methoxy-5-propan-2-yloxyquinazolin-4-yl)amino]-n-methyl-4-(1,1,1-trifluoropropan-2-yloxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(C)C(F)(F)F)C(NC=2C3=C(OC(C)C)C=C(OC)C=C3N=CN=2)=C1 POKHOZHYJRLTBV-UHFFFAOYSA-N 0.000 claims description 2
- UBPZKGHCYGZUKO-UHFFFAOYSA-N 3-[(7-methoxy-5-propan-2-yloxyquinazolin-4-yl)amino]-n-methyl-4-(trifluoromethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(F)(F)F)C(NC=2C3=C(OC(C)C)C=C(OC)C=C3N=CN=2)=C1 UBPZKGHCYGZUKO-UHFFFAOYSA-N 0.000 claims description 2
- DUTAWJOHYORMCO-UHFFFAOYSA-N 3-[[7-(3-chloropropoxy)quinazolin-4-yl]amino]-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC=C(OCCCCl)C=C3N=CN=2)=C1 DUTAWJOHYORMCO-UHFFFAOYSA-N 0.000 claims description 2
- UIBXYETWZDSJHG-UHFFFAOYSA-N 3-[[7-(3-chloropropoxy)quinazolin-4-yl]amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC=C(OCCCCl)C=C3N=CN=2)=C1 UIBXYETWZDSJHG-UHFFFAOYSA-N 0.000 claims description 2
- KQJGPSROODLVCR-UHFFFAOYSA-N 3-[[7-methoxy-5-(oxan-4-yloxy)quinazolin-4-yl]amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=C(OC4CCOCC4)C=C(OC)C=C3N=CN=2)=C1 KQJGPSROODLVCR-UHFFFAOYSA-N 0.000 claims description 2
- DETZHDXVQPOGQN-UHFFFAOYSA-N 4-(4,4-difluoropiperidin-1-yl)-3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methylbenzenesulfonamide Chemical compound N=1C=NC2=CC(OC)=C(OC)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1CCC(F)(F)CC1 DETZHDXVQPOGQN-UHFFFAOYSA-N 0.000 claims description 2
- IYTSEGRKCOLUOI-UHFFFAOYSA-N 4-(dimethylamino)-3-[[7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC(OCCCN4CCOCC4)=C(OC)C=C3N=CN=2)=C1 IYTSEGRKCOLUOI-UHFFFAOYSA-N 0.000 claims description 2
- GXUZZZRWJPJLHA-UHFFFAOYSA-N 4-(dimethylamino)-n-methyl-3-(quinazolin-4-ylamino)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC=CC=C3N=CN=2)=C1 GXUZZZRWJPJLHA-UHFFFAOYSA-N 0.000 claims description 2
- CRLNWEQWLRTEMH-UHFFFAOYSA-N 4-(dimethylamino)-n-methyl-3-[(7-nitroquinazolin-4-yl)amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC=C(C=C3N=CN=2)[N+]([O-])=O)=C1 CRLNWEQWLRTEMH-UHFFFAOYSA-N 0.000 claims description 2
- GSRJICYGMFRKNT-UHFFFAOYSA-N 4-(dimethylamino)-n-methyl-3-[[7-(methylamino)quinazolin-4-yl]amino]benzenesulfonamide Chemical compound N=1C=NC2=CC(NC)=CC=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N(C)C GSRJICYGMFRKNT-UHFFFAOYSA-N 0.000 claims description 2
- VSWVHOWZJGZKRL-UHFFFAOYSA-N 4-methoxy-3-[[7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC)C(NC=2C3=CC(OCCCN4CCOCC4)=C(OC)C=C3N=CN=2)=C1 VSWVHOWZJGZKRL-UHFFFAOYSA-N 0.000 claims description 2
- RNNIWUUBVCLWPJ-UHFFFAOYSA-N 5-[(5,7-dimethoxyquinazolin-4-yl)amino]-2-fluoro-4-methoxy-n-methylbenzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)NC)=CC(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1OC RNNIWUUBVCLWPJ-UHFFFAOYSA-N 0.000 claims description 2
- ZDXFEOAHDUUOHZ-UHFFFAOYSA-N 5-[(5,7-dimethoxyquinazolin-4-yl)amino]-4-(dimethylamino)-2-fluoro-n-methylbenzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)NC)=CC(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1N(C)C ZDXFEOAHDUUOHZ-UHFFFAOYSA-N 0.000 claims description 2
- AYIRDLINUISSDL-UHFFFAOYSA-N 5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2-fluoro-4-methoxy-n-methylbenzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)NC)=CC(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1OC AYIRDLINUISSDL-UHFFFAOYSA-N 0.000 claims description 2
- MRNDDGYEVRTLML-UHFFFAOYSA-N 5-[(6,7-dimethoxyquinazolin-4-yl)amino]-4-(dimethylamino)-2-fluoro-n-methylbenzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)NC)=CC(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1N(C)C MRNDDGYEVRTLML-UHFFFAOYSA-N 0.000 claims description 2
- BCPFKHJCHDHGPM-UHFFFAOYSA-N n-methyl-3-[[7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino]-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC=C(OCCCN4CCOCC4)C=C3N=CN=2)=C1 BCPFKHJCHDHGPM-UHFFFAOYSA-N 0.000 claims description 2
- WWFLLNKYPHEIHC-UHFFFAOYSA-N n-methyl-4-(1,1,1-trifluoropropan-2-yloxy)-3-[(5,6,7-trimethoxyquinazolin-4-yl)amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(C)C(F)(F)F)C(NC=2C3=C(OC)C(OC)=C(OC)C=C3N=CN=2)=C1 WWFLLNKYPHEIHC-UHFFFAOYSA-N 0.000 claims description 2
- POLFXEZBQNZFED-UHFFFAOYSA-N n-methyl-4-(2,2,2-trifluoroethoxy)-3-[(5,6,7-trimethoxyquinazolin-4-yl)amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=C(OC)C(OC)=C(OC)C=C3N=CN=2)=C1 POLFXEZBQNZFED-UHFFFAOYSA-N 0.000 claims description 2
- OPRPIUSDRSRZEJ-UHFFFAOYSA-N n-methyl-4-(trifluoromethoxy)-3-[(5,6,7-trimethoxyquinazolin-4-yl)amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(F)(F)F)C(NC=2C3=C(OC)C(OC)=C(OC)C=C3N=CN=2)=C1 OPRPIUSDRSRZEJ-UHFFFAOYSA-N 0.000 claims description 2
- CYGFUVGTKBARLN-UHFFFAOYSA-N n-methyl-4-methylsulfonyl-3-[(5,6,7-trimethoxyquinazolin-4-yl)amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(S(C)(=O)=O)C(NC=2C3=C(OC)C(OC)=C(OC)C=C3N=CN=2)=C1 CYGFUVGTKBARLN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 8
- MATNUJFSCZJSJO-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-(1,1,1-trifluoropropan-2-yloxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(C)C(F)(F)F)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 MATNUJFSCZJSJO-UHFFFAOYSA-N 0.000 claims 3
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 claims 1
- ZJHCUCIDECWVFH-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-(trifluoromethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(F)(F)F)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 ZJHCUCIDECWVFH-UHFFFAOYSA-N 0.000 claims 1
- MJKMVKRGPQDWFR-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-(trifluoromethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(F)(F)F)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 MJKMVKRGPQDWFR-UHFFFAOYSA-N 0.000 claims 1
- QSDJBUKIGBABSY-UHFFFAOYSA-N 3-[(6-chloroquinazolin-4-yl)amino]-4-(4,4-difluoropiperidin-1-yl)-n-methylbenzenesulfonamide Chemical compound N=1C=NC2=CC=C(Cl)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1CCC(F)(F)CC1 QSDJBUKIGBABSY-UHFFFAOYSA-N 0.000 claims 1
- PLVDPVQBUNFANZ-UHFFFAOYSA-N 3-[(6-chloroquinazolin-4-yl)amino]-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC(Cl)=CC=C3N=CN=2)=C1 PLVDPVQBUNFANZ-UHFFFAOYSA-N 0.000 claims 1
- FFLPSTMYRDDWDO-UHFFFAOYSA-N 3-[(7-ethoxy-6-methoxyquinazolin-4-yl)amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound C=12C=C(OC)C(OCC)=CC2=NC=NC=1NC1=CC(S(=O)(=O)NC)=CC=C1OCC(F)(F)F FFLPSTMYRDDWDO-UHFFFAOYSA-N 0.000 claims 1
- YHXHCUHVCFPSOU-UHFFFAOYSA-N 3-[(7-methoxy-6-propan-2-yloxyquinazolin-4-yl)amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC(OC(C)C)=C(OC)C=C3N=CN=2)=C1 YHXHCUHVCFPSOU-UHFFFAOYSA-N 0.000 claims 1
- ZWUMJTRYDKNMRG-UHFFFAOYSA-N 3-[[6,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino]-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC(OCCOC)=C(OCCOC)C=C3N=CN=2)=C1 ZWUMJTRYDKNMRG-UHFFFAOYSA-N 0.000 claims 1
- PPRVYJPZYHSZOO-UHFFFAOYSA-N 3-[[6,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino]-4-methoxy-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC)C(NC=2C3=CC(OCCOC)=C(OCCOC)C=C3N=CN=2)=C1 PPRVYJPZYHSZOO-UHFFFAOYSA-N 0.000 claims 1
- XHEYFJKKPJBKJN-UHFFFAOYSA-N 3-[[6,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC(OCCOC)=C(OCCOC)C=C3N=CN=2)=C1 XHEYFJKKPJBKJN-UHFFFAOYSA-N 0.000 claims 1
- CEGINXVVTLEPOR-UHFFFAOYSA-N 3-[[6,7-bis(2-methoxyethoxy)quinazolin-4-yl]amino]-n-methyl-4-methylsulfanylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(SC)C(NC=2C3=CC(OCCOC)=C(OCCOC)C=C3N=CN=2)=C1 CEGINXVVTLEPOR-UHFFFAOYSA-N 0.000 claims 1
- VYSMSRYJJVHBRS-UHFFFAOYSA-N 3-[[6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC(OC)=C(OCCOC)C=C3N=CN=2)=C1 VYSMSRYJJVHBRS-UHFFFAOYSA-N 0.000 claims 1
- TWRWCJIUIFYWEW-UHFFFAOYSA-N 3-[[7-methoxy-5-(2-methoxyethoxy)quinazolin-4-yl]amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=C(OCCOC)C=C(OC)C=C3N=CN=2)=C1 TWRWCJIUIFYWEW-UHFFFAOYSA-N 0.000 claims 1
- FFRWTFPJRTXJRL-UHFFFAOYSA-N 4-(dimethylamino)-3-[(6-methoxyquinazolin-4-yl)amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC(OC)=CC=C3N=CN=2)=C1 FFRWTFPJRTXJRL-UHFFFAOYSA-N 0.000 claims 1
- BWIUPWHYSIZHBS-UHFFFAOYSA-N 4-(dimethylamino)-3-[[7-(3-methoxypropoxy)quinazolin-4-yl]amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC=C(OCCCOC)C=C3N=CN=2)=C1 BWIUPWHYSIZHBS-UHFFFAOYSA-N 0.000 claims 1
- QYAZLRALCQRFSU-UHFFFAOYSA-N 4-(dimethylamino)-n-methyl-3-[[7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC=C(OCCCN4CCOCC4)C=C3N=CN=2)=C1 QYAZLRALCQRFSU-UHFFFAOYSA-N 0.000 claims 1
- OMDSXORUDUAWTD-UHFFFAOYSA-N 4-chloro-n-methyl-3-[(5,6,7-trimethoxyquinazolin-4-yl)amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Cl)C(NC=2C3=C(OC)C(OC)=C(OC)C=C3N=CN=2)=C1 OMDSXORUDUAWTD-UHFFFAOYSA-N 0.000 claims 1
- NZWRDZOEFIJLTE-UHFFFAOYSA-N 5-[(5,7-dimethoxyquinazolin-4-yl)amino]-2-fluoro-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)NC)=CC(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1OCC(F)(F)F NZWRDZOEFIJLTE-UHFFFAOYSA-N 0.000 claims 1
- GJZBPODRSHTVIA-UHFFFAOYSA-N 5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2-fluoro-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)NC)=CC(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1OCC(F)(F)F GJZBPODRSHTVIA-UHFFFAOYSA-N 0.000 claims 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 212
- 238000005481 NMR spectroscopy Methods 0.000 description 109
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000000203 mixture Substances 0.000 description 77
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
- 125000000217 alkyl group Chemical group 0.000 description 68
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 62
- 239000007787 solid Substances 0.000 description 56
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 48
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 43
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 42
- 229940124530 sulfonamide Drugs 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 35
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- 235000019439 ethyl acetate Nutrition 0.000 description 31
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 29
- YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- JVLFMTZUPSBCNJ-UHFFFAOYSA-N 3,5-difluoropyridin-2-amine Chemical compound NC1=NC=C(F)C=C1F JVLFMTZUPSBCNJ-UHFFFAOYSA-N 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- 150000003456 sulfonamides Chemical class 0.000 description 25
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical class N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 24
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 22
- 150000001555 benzenes Chemical class 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 239000007983 Tris buffer Substances 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- 238000011282 treatment Methods 0.000 description 20
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- LQVXSNNAFNGRAH-QHCPKHFHSA-N BMS-754807 Chemical compound C([C@@]1(C)C(=O)NC=2C=NC(F)=CC=2)CCN1C(=NN1C=CC=C11)N=C1NC(=NN1)C=C1C1CC1 LQVXSNNAFNGRAH-QHCPKHFHSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 125000001188 haloalkyl group Chemical group 0.000 description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- PRTLSVYSOPRSIX-UHFFFAOYSA-N 4-fluoro-n-methyl-3-nitrobenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(F)C([N+]([O-])=O)=C1 PRTLSVYSOPRSIX-UHFFFAOYSA-N 0.000 description 11
- USQCUKQZXOWUDF-YWZLYKJASA-N 6-chloro-n-[(3s)-1-[(2s)-1-(4-methyl-5-oxo-1,4-diazepan-1-yl)-1-oxopropan-2-yl]-2-oxopyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound O=C([C@@H](N1C([C@@H](NS(=O)(=O)C=2C=C3C=CC(Cl)=CC3=CC=2)CC1)=O)C)N1CCN(C)C(=O)CC1 USQCUKQZXOWUDF-YWZLYKJASA-N 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- 239000007832 Na2SO4 Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 9
- 208000006029 Cardiomegaly Diseases 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- 239000012453 solvate Substances 0.000 description 9
- CLATWDTWMVIPHK-UHFFFAOYSA-N 5-[2-[[3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzoyl]amino]ethylcarbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid Chemical compound CC1=CC=C(O)C=C1NC1=CC=NC(NC=2C=C(C=CC=2)C(=O)NCCNC(=O)C=2C=C(C(=CC=2)C2=C3C=CC(=O)C=C3OC3=CC(O)=CC=C32)C(O)=O)=N1 CLATWDTWMVIPHK-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 150000004677 hydrates Chemical class 0.000 description 7
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- UZMKAUCMFAEBKM-UHFFFAOYSA-N 2-methylbenzenesulfonamide toluene Chemical compound CC1=CC=CC=C1.CC1=CC=CC=C1S(N)(=O)=O UZMKAUCMFAEBKM-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- BPSUJSDZHLTNJR-UHFFFAOYSA-N sulfamide;hydrochloride Chemical compound Cl.NS(N)(=O)=O BPSUJSDZHLTNJR-UHFFFAOYSA-N 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- IEGGPINENROAPG-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-(1,1,1-trifluoropropan-2-yloxy)benzenesulfonamide;hydrochloride Chemical compound Cl.CNS(=O)(=O)C1=CC=C(OC(C)C(F)(F)F)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 IEGGPINENROAPG-UHFFFAOYSA-N 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 5
- 150000003246 quinazolines Chemical class 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- GQHWSLKNULCZGI-UHFFFAOYSA-N trifluoromethoxybenzene Chemical compound FC(F)(F)OC1=CC=CC=C1 GQHWSLKNULCZGI-UHFFFAOYSA-N 0.000 description 5
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 150000001350 alkyl halides Chemical class 0.000 description 4
- DKPBWQKQXNICDH-UHFFFAOYSA-N aniline;quinazoline Chemical compound NC1=CC=CC=C1.N1=CN=CC2=CC=CC=C21 DKPBWQKQXNICDH-UHFFFAOYSA-N 0.000 description 4
- 150000001448 anilines Chemical class 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 102000049185 human TNNI3K Human genes 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 230000010287 polarization Effects 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 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 4
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 3
- BBNCAUCNCDIBQL-UHFFFAOYSA-N 2,4-difluoro-n-methyl-5-nitrobenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC([N+]([O-])=O)=C(F)C=C1F BBNCAUCNCDIBQL-UHFFFAOYSA-N 0.000 description 3
- RJEYXRJFAIYPDD-UHFFFAOYSA-N 2-fluoro-n-methyl-5-nitro-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC([N+]([O-])=O)=C(OCC(F)(F)F)C=C1F RJEYXRJFAIYPDD-UHFFFAOYSA-N 0.000 description 3
- ZFFUFWXJBDZZFV-UHFFFAOYSA-N 2-fluoro-n-methyl-5-nitrobenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC([N+]([O-])=O)=CC=C1F ZFFUFWXJBDZZFV-UHFFFAOYSA-N 0.000 description 3
- CUTDVRNTTBYVDZ-UHFFFAOYSA-N 3-[(6-methoxy-7-phenylmethoxyquinazolin-4-yl)amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC(OC)=C(OCC=4C=CC=CC=4)C=C3N=CN=2)=C1 CUTDVRNTTBYVDZ-UHFFFAOYSA-N 0.000 description 3
- HQCSMPOAVQPAQQ-UHFFFAOYSA-N 3-amino-4-chloro-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Cl)C(N)=C1 HQCSMPOAVQPAQQ-UHFFFAOYSA-N 0.000 description 3
- AWWJQWXSWOWSQP-UHFFFAOYSA-N 3-amino-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(N)=C1 AWWJQWXSWOWSQP-UHFFFAOYSA-N 0.000 description 3
- XQEDHQMPIHJWMV-UHFFFAOYSA-N 3-amino-n-methyl-4-[methyl(2,2,2-trifluoroethyl)amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)CC(F)(F)F)C(N)=C1 XQEDHQMPIHJWMV-UHFFFAOYSA-N 0.000 description 3
- BJJFJTDSMDVFIJ-UHFFFAOYSA-N 3-amino-n-methyl-4-methylsulfanylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(SC)C(N)=C1 BJJFJTDSMDVFIJ-UHFFFAOYSA-N 0.000 description 3
- AFDQDEYJUOLHMP-UHFFFAOYSA-N 3-amino-n-methyl-4-methylsulfonylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(S(C)(=O)=O)C(N)=C1 AFDQDEYJUOLHMP-UHFFFAOYSA-N 0.000 description 3
- XVQMWFGOFRXMHE-UHFFFAOYSA-N 3-amino-n-methyl-4-morpholin-4-ylbenzenesulfonamide Chemical compound NC1=CC(S(=O)(=O)NC)=CC=C1N1CCOCC1 XVQMWFGOFRXMHE-UHFFFAOYSA-N 0.000 description 3
- NFUZPVIWFUFFJA-UHFFFAOYSA-N 3-amino-n-methyl-4-propan-2-yloxybenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(C)C)C(N)=C1 NFUZPVIWFUFFJA-UHFFFAOYSA-N 0.000 description 3
- XZLYLEIECXYKNJ-UHFFFAOYSA-N 4,5,6-trimethoxy-1h-indole-2,3-dione Chemical compound COC1=C(OC)C(OC)=CC2=C1C(=O)C(=O)N2 XZLYLEIECXYKNJ-UHFFFAOYSA-N 0.000 description 3
- WFOSGTNBNISVKE-UHFFFAOYSA-N 4-(dimethylamino)-2-fluoro-n-methyl-5-nitrobenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC([N+]([O-])=O)=C(N(C)C)C=C1F WFOSGTNBNISVKE-UHFFFAOYSA-N 0.000 description 3
- LLLHRNQLGUOJHP-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C=C(OC)C(OC)=CC2=N1 LLLHRNQLGUOJHP-UHFFFAOYSA-N 0.000 description 3
- DEETUTHTBFVLAH-UHFFFAOYSA-N 4-chloro-6-ethoxy-7-methoxyquinazoline Chemical compound N1=CN=C2C=C(OC)C(OCC)=CC2=C1Cl DEETUTHTBFVLAH-UHFFFAOYSA-N 0.000 description 3
- UMNGEAKUUOJPAX-UHFFFAOYSA-N 4-chloro-n-methyl-3-nitrobenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 UMNGEAKUUOJPAX-UHFFFAOYSA-N 0.000 description 3
- DGQAPUDRPYXACW-UHFFFAOYSA-N 5-amino-2-fluoro-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC(N)=C(OCC(F)(F)F)C=C1F DGQAPUDRPYXACW-UHFFFAOYSA-N 0.000 description 3
- PFEAQGIRENOXFR-UHFFFAOYSA-N 5-amino-2-fluoro-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC(N)=CC=C1F PFEAQGIRENOXFR-UHFFFAOYSA-N 0.000 description 3
- BTBJBAAVDLVBFK-UHFFFAOYSA-N 5-amino-4-(dimethylamino)-2-fluoro-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC(N)=C(N(C)C)C=C1F BTBJBAAVDLVBFK-UHFFFAOYSA-N 0.000 description 3
- GQBCDMUMKMBTME-UHFFFAOYSA-N 6-amino-2,3,4-trimethoxybenzoic acid Chemical compound COC1=CC(N)=C(C(O)=O)C(OC)=C1OC GQBCDMUMKMBTME-UHFFFAOYSA-N 0.000 description 3
- LWYYBCHNCHYKFF-UHFFFAOYSA-N 6-ethoxy-7-methoxy-1h-quinazolin-4-one Chemical compound N1=CN=C2C=C(OC)C(OCC)=CC2=C1O LWYYBCHNCHYKFF-UHFFFAOYSA-N 0.000 description 3
- 239000005541 ACE inhibitor Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229940125364 angiotensin receptor blocker Drugs 0.000 description 3
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- UZPUUYBBKZVODX-UHFFFAOYSA-N benzyl N-[(4-fluoro-3-nitrophenyl)sulfonylmethyl]carbamate Chemical compound C1(=CC=CC=C1)COC(NCS(=O)(=O)C1=CC(=C(C=C1)F)[N+](=O)[O-])=O UZPUUYBBKZVODX-UHFFFAOYSA-N 0.000 description 3
- MGSRRJIXSRBPDW-UHFFFAOYSA-N benzyl n-methyl-n-[3-nitro-4-(2,2,2-trifluoroethylamino)phenyl]sulfonylcarbamate Chemical compound C=1C=C(NCC(F)(F)F)C([N+]([O-])=O)=CC=1S(=O)(=O)N(C)C(=O)OCC1=CC=CC=C1 MGSRRJIXSRBPDW-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- 125000001786 isothiazolyl group Chemical group 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- RMNSHLCXEJWRHQ-UHFFFAOYSA-N methyl 6-amino-2,3,4-trimethoxybenzoate Chemical compound COC(=O)C1=C(N)C=C(OC)C(OC)=C1OC RMNSHLCXEJWRHQ-UHFFFAOYSA-N 0.000 description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 230000000116 mitigating effect Effects 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 208000031225 myocardial ischemia Diseases 0.000 description 3
- AQSFJSXSHHVVPT-UHFFFAOYSA-N n-methyl-3-nitro-4-propan-2-yloxybenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC(C)C)C([N+]([O-])=O)=C1 AQSFJSXSHHVVPT-UHFFFAOYSA-N 0.000 description 3
- VZODTLCCJGMYTG-UHFFFAOYSA-N n-methyl-4-methylsulfanyl-3-nitrobenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(SC)C([N+]([O-])=O)=C1 VZODTLCCJGMYTG-UHFFFAOYSA-N 0.000 description 3
- QXIGNECYDYTSAF-UHFFFAOYSA-N n-methyl-4-methylsulfonyl-3-nitrobenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(S(C)(=O)=O)C([N+]([O-])=O)=C1 QXIGNECYDYTSAF-UHFFFAOYSA-N 0.000 description 3
- ZDUSNUAEXDDJAQ-UHFFFAOYSA-N n-methyl-4-morpholin-4-yl-3-nitrobenzenesulfonamide Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)NC)=CC=C1N1CCOCC1 ZDUSNUAEXDDJAQ-UHFFFAOYSA-N 0.000 description 3
- 239000008184 oral solid dosage form Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 2
- ILWJAOPQHOZXAN-UHFFFAOYSA-N 1,3-dithianyl Chemical group [CH]1SCCCS1 ILWJAOPQHOZXAN-UHFFFAOYSA-N 0.000 description 2
- ARGPEMOBEZXYNR-UHFFFAOYSA-N 1-(trifluoromethoxy)-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)OC1=CC=CC=C1C(F)(F)F ARGPEMOBEZXYNR-UHFFFAOYSA-N 0.000 description 2
- RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 description 2
- XAZYVFJSHFBTTM-UHFFFAOYSA-N 2,4-difluoro-5-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC(S(Cl)(=O)=O)=C(F)C=C1F XAZYVFJSHFBTTM-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- XJBHIZXBVPGRHH-UHFFFAOYSA-N 2-fluoro-5-nitro-4-(2,2,2-trifluoroethoxy)benzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC(S(Cl)(=O)=O)=C(F)C=C1OCC(F)(F)F XJBHIZXBVPGRHH-UHFFFAOYSA-N 0.000 description 2
- VQHGELUKJYOETQ-UHFFFAOYSA-N 2-fluoro-5-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(F)C(S(Cl)(=O)=O)=C1 VQHGELUKJYOETQ-UHFFFAOYSA-N 0.000 description 2
- UZHBBILMZZCORA-UHFFFAOYSA-N 3,4-dihydro-2H-pyrrole toluene 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.CC1=CC=CC=C1.N1=CCCC1 UZHBBILMZZCORA-UHFFFAOYSA-N 0.000 description 2
- DRNFVVOPBSUMIR-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide;hydrochloride Chemical compound Cl.CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 DRNFVVOPBSUMIR-UHFFFAOYSA-N 0.000 description 2
- BBIXKPAPONZNKE-UHFFFAOYSA-N 3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-methylsulfonylbenzenesulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CNS(=O)(=O)C1=CC=C(S(C)(=O)=O)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 BBIXKPAPONZNKE-UHFFFAOYSA-N 0.000 description 2
- YKIVGQKMBXBJHS-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-n-methyl-4-(2,2,2-trifluoroethoxy)benzenesulfonamide;hydrochloride Chemical compound Cl.CNS(=O)(=O)C1=CC=C(OCC(F)(F)F)C(NC=2C3=CC(OC)=C(OC)C=C3N=CN=2)=C1 YKIVGQKMBXBJHS-UHFFFAOYSA-N 0.000 description 2
- WSLMCPFAPFZVIY-UHFFFAOYSA-N 3-amino-4-(dimethylamino)-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(N)=C1 WSLMCPFAPFZVIY-UHFFFAOYSA-N 0.000 description 2
- UXLLDUXIDDMANK-UHFFFAOYSA-N 3-amino-4-fluoro-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(F)C(N)=C1 UXLLDUXIDDMANK-UHFFFAOYSA-N 0.000 description 2
- JUDHRKDDXFHONV-UHFFFAOYSA-N 4,5-dichloro-6,7-dimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C(Cl)=C(OC)C(OC)=CC2=N1 JUDHRKDDXFHONV-UHFFFAOYSA-N 0.000 description 2
- INCGOLYDSSEPDS-UHFFFAOYSA-N 4-(dimethylamino)-n-methyl-3-(quinazolin-4-ylamino)benzenesulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC=CC=C3N=CN=2)=C1 INCGOLYDSSEPDS-UHFFFAOYSA-N 0.000 description 2
- XJCQYMYLFKKZLX-UHFFFAOYSA-N 4-chloro-5-ethoxy-7-methoxyquinazoline Chemical compound C1=NC(Cl)=C2C(OCC)=CC(OC)=CC2=N1 XJCQYMYLFKKZLX-UHFFFAOYSA-N 0.000 description 2
- GVRRXASZZAKBMN-UHFFFAOYSA-N 4-chloroquinazoline Chemical class C1=CC=C2C(Cl)=NC=NC2=C1 GVRRXASZZAKBMN-UHFFFAOYSA-N 0.000 description 2
- USOVRXNIZFSGEU-UHFFFAOYSA-N 4-fluoro-1-nitro-2-(2,2,2-trifluoroethoxy)benzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1OCC(F)(F)F USOVRXNIZFSGEU-UHFFFAOYSA-N 0.000 description 2
- RRONENSZKCGROA-UHFFFAOYSA-N 4-fluoro-3-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC(S(Cl)(=O)=O)=CC=C1F RRONENSZKCGROA-UHFFFAOYSA-N 0.000 description 2
- JLFAHVDBMXMNLK-UHFFFAOYSA-N 5,6,7-trimethoxy-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=C1C=C(OC)C(OC)=C2OC JLFAHVDBMXMNLK-UHFFFAOYSA-N 0.000 description 2
- LWFCXCUIINZJIQ-UHFFFAOYSA-N 5-ethoxy-7-methoxy-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=C1C=C(OC)C=C2OCC LWFCXCUIINZJIQ-UHFFFAOYSA-N 0.000 description 2
- 229940123338 Aldosterone synthase inhibitor Drugs 0.000 description 2
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 102100036725 Epithelial discoidin domain-containing receptor 1 Human genes 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 206010020880 Hypertrophy Diseases 0.000 description 2
- 108010007859 Lisinopril Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 description 2
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 2
- 241001024304 Mino Species 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- AEKNYBWUEYNWMJ-QWOOXDRHSA-N Pramiconazole Chemical compound O=C1N(C(C)C)CCN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(CO3)C=3C(=CC(F)=CC=3)F)=CC=2)C=C1 AEKNYBWUEYNWMJ-QWOOXDRHSA-N 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 240000006394 Sorghum bicolor Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229960004530 benazepril Drugs 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 229940097320 beta blocking agent Drugs 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000000480 calcium channel blocker Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 150000001975 deuterium Chemical group 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 2
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 230000001882 diuretic effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 210000005003 heart tissue Anatomy 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229960002394 lisinopril Drugs 0.000 description 2
- CZRQXSDBMCMPNJ-ZUIPZQNBSA-N lisinopril dihydrate Chemical compound O.O.C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 CZRQXSDBMCMPNJ-ZUIPZQNBSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000005172 methylbenzenes Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 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 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000005968 oxazolinyl group Chemical group 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000002755 pyrazolinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 229960003401 ramipril Drugs 0.000 description 2
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 239000002461 renin inhibitor Substances 0.000 description 2
- 229940086526 renin-inhibitors Drugs 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000002769 thiazolinyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 125000004306 triazinyl group Chemical group 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 2
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 1
- CEMAWMOMDPGJMB-UHFFFAOYSA-N (+-)-Oxprenolol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1OCC=C CEMAWMOMDPGJMB-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- TXSINLUUGRGAJO-WCBMZHEXSA-N (2s)-2-[[(2s)-2-(1,3-benzodioxol-5-ylmethyl)-3-sulfanylpropanoyl]amino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](CS)CC1=CC=C2OCOC2=C1 TXSINLUUGRGAJO-WCBMZHEXSA-N 0.000 description 1
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 1
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
- VHGJDIMTOSCCOX-UHFFFAOYSA-N (5-hydroxy-7-methoxy-4-oxoquinazolin-3-yl)methyl 2,2-dimethylpropanoate Chemical compound N1=CN(COC(=O)C(C)(C)C)C(=O)C=2C1=CC(OC)=CC=2O VHGJDIMTOSCCOX-UHFFFAOYSA-N 0.000 description 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- KOHIRBRYDXPAMZ-YHBROIRLSA-N (S,R,R,R)-nebivolol Chemical compound C1CC2=CC(F)=CC=C2O[C@H]1[C@H](O)CNC[C@@H](O)[C@H]1OC2=CC=C(F)C=C2CC1 KOHIRBRYDXPAMZ-YHBROIRLSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- KFHQOZXAFUKFNB-UHFFFAOYSA-N 1,3-oxathiolanyl Chemical group [CH]1OCCS1 KFHQOZXAFUKFNB-UHFFFAOYSA-N 0.000 description 1
- QNGAMZHJFDJCSL-UHFFFAOYSA-N 1-ethoxy-7-methoxyquinazolin-4-one Chemical compound C(C)ON1C=NC(C2=CC=C(C=C12)OC)=O QNGAMZHJFDJCSL-UHFFFAOYSA-N 0.000 description 1
- JUVHOTUQNFWSOU-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene 4-fluoro-3-nitrobenzenesulfonyl chloride Chemical compound FC1=C(C=CC=C1)[N+](=O)[O-].FC1=C(C=C(C=C1)S(=O)(=O)Cl)[N+](=O)[O-] JUVHOTUQNFWSOU-UHFFFAOYSA-N 0.000 description 1
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical class OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- FBMYKMYQHCBIGU-UHFFFAOYSA-N 2-[2-hydroxy-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile Chemical compound C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1C#N FBMYKMYQHCBIGU-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- JMBYAWCJPNQXAA-UHFFFAOYSA-N 2-chloro-5-ethoxy-7-methoxyquinazoline Chemical compound ClC1=NC2=CC(=CC(=C2C=N1)OCC)OC JMBYAWCJPNQXAA-UHFFFAOYSA-N 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical class OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- BWYJJZBRYSADRP-UHFFFAOYSA-N 2-methoxyquinazoline Chemical compound C1=CC=CC2=NC(OC)=NC=C21 BWYJJZBRYSADRP-UHFFFAOYSA-N 0.000 description 1
- DJWRXYSXZYZTEP-UHFFFAOYSA-N 2-methylbenzenesulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1=CC=CC=C1S(N)(=O)=O DJWRXYSXZYZTEP-UHFFFAOYSA-N 0.000 description 1
- NMKSAYKQLCHXDK-UHFFFAOYSA-N 3,3-diphenyl-N-(1-phenylethyl)-1-propanamine Chemical compound C=1C=CC=CC=1C(C)NCCC(C=1C=CC=CC=1)C1=CC=CC=C1 NMKSAYKQLCHXDK-UHFFFAOYSA-N 0.000 description 1
- XEFRNCLPPFDWAC-UHFFFAOYSA-N 3,4,5-trimethoxyaniline Chemical compound COC1=CC(N)=CC(OC)=C1OC XEFRNCLPPFDWAC-UHFFFAOYSA-N 0.000 description 1
- MACJBQSESOYMOK-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinazolin-4-yl)amino]-4-(2,5-dimethylpyrrolidin-1-yl)-n-methylbenzenesulfonamide Chemical compound N=1C=NC2=CC(OC)=C(OC)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1C(C)CCC1C MACJBQSESOYMOK-UHFFFAOYSA-N 0.000 description 1
- MLFAJHNXGPPEPF-UHFFFAOYSA-N 3-[(6-chloroquinazolin-4-yl)amino]-4-(2,5-dimethylpyrrolidin-1-yl)-n-methylbenzenesulfonamide Chemical compound N=1C=NC2=CC=C(Cl)C=C2C=1NC1=CC(S(=O)(=O)NC)=CC=C1N1C(C)CCC1C MLFAJHNXGPPEPF-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NVZINPVISUVPHW-UHFFFAOYSA-N 3-methylbenzenesulfonamide Chemical compound CC1=CC=CC(S(N)(=O)=O)=C1 NVZINPVISUVPHW-UHFFFAOYSA-N 0.000 description 1
- CLPFFLWZZBQMAO-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1N2C=NC=C2CCC1 CLPFFLWZZBQMAO-UHFFFAOYSA-N 0.000 description 1
- RPBHXDRVEXZQBS-UHFFFAOYSA-N 4-(dimethylamino)-3-[[6-(dimethylamino)quinazolin-4-yl]amino]-n-methylbenzenesulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC(=CC=C3N=CN=2)N(C)C)=C1 RPBHXDRVEXZQBS-UHFFFAOYSA-N 0.000 description 1
- OEYOZBYTLZVZFT-UHFFFAOYSA-N 4-(dimethylamino)-n-methyl-3-[(6-nitroquinazolin-4-yl)amino]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC(=CC=C3N=CN=2)[N+]([O-])=O)=C1 OEYOZBYTLZVZFT-UHFFFAOYSA-N 0.000 description 1
- XGFIHOJEQCXAQE-UHFFFAOYSA-N 4-(dimethylamino)-n-methyl-3-[[7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino]benzenesulfonamide;hydrochloride Chemical compound Cl.CNS(=O)(=O)C1=CC=C(N(C)C)C(NC=2C3=CC=C(OCCCN4CCOCC4)C=C3N=CN=2)=C1 XGFIHOJEQCXAQE-UHFFFAOYSA-N 0.000 description 1
- SEWNAJIUKSTYOP-UHFFFAOYSA-N 4-chloro-3-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC(S(Cl)(=O)=O)=CC=C1Cl SEWNAJIUKSTYOP-UHFFFAOYSA-N 0.000 description 1
- MUIRIRMDOFREES-UHFFFAOYSA-N 4-chloro-5,6,7-trimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C(OC)=C(OC)C(OC)=CC2=N1 MUIRIRMDOFREES-UHFFFAOYSA-N 0.000 description 1
- BTGIKZVZNHHDAU-UHFFFAOYSA-N 4-chloro-5,7-dimethoxyquinazoline Chemical compound ClC1=NC=NC2=CC(OC)=CC(OC)=C21 BTGIKZVZNHHDAU-UHFFFAOYSA-N 0.000 description 1
- LBGIYCBNJBHZSZ-UHFFFAOYSA-N 4-chloro-6-methoxy-7-phenylmethoxyquinazoline Chemical compound COC1=CC2=C(Cl)N=CN=C2C=C1OCC1=CC=CC=C1 LBGIYCBNJBHZSZ-UHFFFAOYSA-N 0.000 description 1
- YNIDWSPWODDHRB-UHFFFAOYSA-N 4-methylbenzenesulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1.CC1=CC=C(S(N)(=O)=O)C=C1 YNIDWSPWODDHRB-UHFFFAOYSA-N 0.000 description 1
- SUFLIOBGIKOXTI-UHFFFAOYSA-N 5-chloro-6,7-dimethoxy-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=C1C=C(OC)C(OC)=C2Cl SUFLIOBGIKOXTI-UHFFFAOYSA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- OKZIRNNFVQCDSA-UHFFFAOYSA-N 6-hydroxy-7-methoxy-1h-quinazolin-4-one Chemical compound C1=NC(O)=C2C=C(O)C(OC)=CC2=N1 OKZIRNNFVQCDSA-UHFFFAOYSA-N 0.000 description 1
- 125000006164 6-membered heteroaryl group Chemical group 0.000 description 1
- 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 1
- FHHHOYXPRDYHEZ-COXVUDFISA-N Alacepril Chemical compound CC(=O)SC[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FHHHOYXPRDYHEZ-COXVUDFISA-N 0.000 description 1
- JBMKAUGHUNFTOL-UHFFFAOYSA-N Aldoclor Chemical class C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O JBMKAUGHUNFTOL-UHFFFAOYSA-N 0.000 description 1
- UXOWGYHJODZGMF-QORCZRPOSA-N Aliskiren Chemical group COCCCOC1=CC(C[C@@H](C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=CC=C1OC UXOWGYHJODZGMF-QORCZRPOSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004382 Amylase Substances 0.000 description 1
- 102000013142 Amylases Human genes 0.000 description 1
- 108010065511 Amylases Proteins 0.000 description 1
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000002080 C09CA02 - Eprosartan Substances 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002081 C09CA05 - Tasosartan Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- SWLTWLLKBZBXQI-UHFFFAOYSA-N COC1=C2C(N=CNC2=CC(=C1OC)OC)=O.ClC1=NC=NC2=CC(=C(C(=C12)OC)OC)OC Chemical compound COC1=C2C(N=CNC2=CC(=C1OC)OC)=O.ClC1=NC=NC2=CC(=C(C(=C12)OC)OC)OC SWLTWLLKBZBXQI-UHFFFAOYSA-N 0.000 description 1
- JPNQAUAAVMWNHK-UHFFFAOYSA-N COC1=CC=C2C=NC=NC2=C1.BrC(C)C Chemical compound COC1=CC=C2C=NC=NC2=C1.BrC(C)C JPNQAUAAVMWNHK-UHFFFAOYSA-N 0.000 description 1
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- JOATXPAWOHTVSZ-UHFFFAOYSA-N Celiprolol Chemical compound CCN(CC)C(=O)NC1=CC=C(OCC(O)CNC(C)(C)C)C(C(C)=O)=C1 JOATXPAWOHTVSZ-UHFFFAOYSA-N 0.000 description 1
- IFYLTXNCFVRALQ-OALUTQOASA-N Ceronapril Chemical compound O([C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)P(O)(=O)CCCCC1=CC=CC=C1 IFYLTXNCFVRALQ-OALUTQOASA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010052337 Diastolic dysfunction Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 239000001692 EU approved anti-caking agent Substances 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 108010066671 Enalaprilat Proteins 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- XQLWNAFCTODIRK-UHFFFAOYSA-N Gallopamil Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC(OC)=C(OC)C(OC)=C1 XQLWNAFCTODIRK-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- WDZVGELJXXEGPV-YIXHJXPBSA-N Guanabenz Chemical compound NC(N)=N\N=C\C1=C(Cl)C=CC=C1Cl WDZVGELJXXEGPV-YIXHJXPBSA-N 0.000 description 1
- INJOMKTZOLKMBF-UHFFFAOYSA-N Guanfacine Chemical compound NC(=N)NC(=O)CC1=C(Cl)C=CC=C1Cl INJOMKTZOLKMBF-UHFFFAOYSA-N 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- CESYKOGBSMNBPD-UHFFFAOYSA-N Methyclothiazide Chemical compound ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CCl)NC2=C1 CESYKOGBSMNBPD-UHFFFAOYSA-N 0.000 description 1
- HBNPJJILLOYFJU-VMPREFPWSA-N Mibefradil Chemical compound C1CC2=CC(F)=CC=C2[C@H](C(C)C)[C@@]1(OC(=O)COC)CCN(C)CCCC1=NC2=CC=CC=C2N1 HBNPJJILLOYFJU-VMPREFPWSA-N 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical class COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
- 239000005480 Olmesartan Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- IFFPICMESYHZPQ-UHFFFAOYSA-N Prenylamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)CCNC(C)CC1=CC=CC=C1 IFFPICMESYHZPQ-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 101710178685 Serine/threonine-protein kinase TNNI3K Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 206010071436 Systolic dysfunction Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ZROUQTNYPCANTN-UHFFFAOYSA-N Tiapamil Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC1(C=2C=C(OC)C(OC)=CC=2)S(=O)(=O)CCCS1(=O)=O ZROUQTNYPCANTN-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 102000013394 Troponin I Human genes 0.000 description 1
- 108010065729 Troponin I Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960002122 acebutolol Drugs 0.000 description 1
- GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical compound CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229950007884 alacepril Drugs 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229960004601 aliskiren Drugs 0.000 description 1
- 229940061720 alpha hydroxy acid Drugs 0.000 description 1
- 150000001280 alpha hydroxy acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 1
- 229960002576 amiloride Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 235000019418 amylase Nutrition 0.000 description 1
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- PHFDAOXXIZOUIX-UHFFFAOYSA-N anipamil Chemical compound C=1C=CC(OC)=CC=1C(CCCCCCCCCCCC)(C#N)CCCN(C)CCC1=CC=CC(OC)=C1 PHFDAOXXIZOUIX-UHFFFAOYSA-N 0.000 description 1
- 229950011530 anipamil Drugs 0.000 description 1
- RLUXVCZBKDVAFS-UHFFFAOYSA-N anisole;methanol Chemical compound OC.COC1=CC=CC=C1 RLUXVCZBKDVAFS-UHFFFAOYSA-N 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- LZLOFGMGFADIKQ-UHFFFAOYSA-N benzene;1,4-dioxane Chemical compound C1COCCO1.C1=CC=CC=C1 LZLOFGMGFADIKQ-UHFFFAOYSA-N 0.000 description 1
- WDMKMBJXZCMVQS-UHFFFAOYSA-N benzene;2,2,2-trifluoroacetic acid Chemical compound C1=CC=CC=C1.OC(=O)C(F)(F)F WDMKMBJXZCMVQS-UHFFFAOYSA-N 0.000 description 1
- WCDLYIMICFUTPX-UHFFFAOYSA-N benzenesulfonamide methoxyethane Chemical compound C1(=CC=CC=C1)S(=O)(=O)N.COCC WCDLYIMICFUTPX-UHFFFAOYSA-N 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- KKBIUAUSZKGNOA-HNAYVOBHSA-N benzyl (2s)-2-[[(2s)-2-(acetylsulfanylmethyl)-3-(1,3-benzodioxol-5-yl)propanoyl]amino]propanoate Chemical compound O=C([C@@H](NC(=O)[C@@H](CSC(C)=O)CC=1C=C2OCOC2=CC=1)C)OCC1=CC=CC=C1 KKBIUAUSZKGNOA-HNAYVOBHSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- MFEBBYPCFNOSQB-UHFFFAOYSA-N benzyl n-methyl-n-[4-[methyl(2,2,2-trifluoroethyl)amino]-3-nitrophenyl]sulfonylcarbamate Chemical compound C1=C([N+]([O-])=O)C(N(CC(F)(F)F)C)=CC=C1S(=O)(=O)N(C)C(=O)OCC1=CC=CC=C1 MFEBBYPCFNOSQB-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229960004324 betaxolol Drugs 0.000 description 1
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 229960002781 bisoprolol Drugs 0.000 description 1
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229950005341 bucindolol Drugs 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001723 carbon free-radicals Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 229960001222 carteolol Drugs 0.000 description 1
- LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 1
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 1
- 229960004195 carvedilol Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229960002320 celiprolol Drugs 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
- 229950005749 ceronapril Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960002155 chlorothiazide Drugs 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 229960005025 cilazapril Drugs 0.000 description 1
- HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000009091 contractile dysfunction Effects 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000005534 decanoate group Chemical class 0.000 description 1
- 229960005227 delapril Drugs 0.000 description 1
- WOUOLAUOZXOLJQ-MBSDFSHPSA-N delapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N(CC(O)=O)C1CC2=CC=CC=C2C1)CC1=CC=CC=C1 WOUOLAUOZXOLJQ-MBSDFSHPSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- BAVYZALUXZFZLV-MICDWDOJSA-N deuteriomethanamine Chemical class [2H]CN BAVYZALUXZFZLV-MICDWDOJSA-N 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 229960002680 enalaprilat Drugs 0.000 description 1
- MZYVOFLIPYDBGD-MLZQUWKJSA-N enalaprilat dihydrate Chemical compound O.O.C([C@H](N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 MZYVOFLIPYDBGD-MLZQUWKJSA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229960001208 eplerenone Drugs 0.000 description 1
- JUKPWJGBANNWMW-VWBFHTRKSA-N eplerenone Chemical compound C([C@@H]1[C@]2(C)C[C@H]3O[C@]33[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)C(=O)OC)C[C@@]21CCC(=O)O1 JUKPWJGBANNWMW-VWBFHTRKSA-N 0.000 description 1
- OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 description 1
- 229960004563 eprosartan Drugs 0.000 description 1
- 229960003745 esmolol Drugs 0.000 description 1
- AQNDDEOPVVGCPG-UHFFFAOYSA-N esmolol Chemical compound COC(=O)CCC1=CC=C(OCC(O)CNC(C)C)C=C1 AQNDDEOPVVGCPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 229960000255 exemestane Drugs 0.000 description 1
- 229950011548 fadrozole Drugs 0.000 description 1
- 229950005203 fasidotril Drugs 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 229960002602 fendiline Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- SMANXXCATUTDDT-QPJJXVBHSA-N flunarizine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCN(C\C=C\C=2C=CC=CC=2)CC1 SMANXXCATUTDDT-QPJJXVBHSA-N 0.000 description 1
- 229960000326 flunarizine Drugs 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 229960002490 fosinopril Drugs 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229960000457 gallopamil Drugs 0.000 description 1
- 238000001030 gas--liquid chromatography Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 229960004553 guanabenz Drugs 0.000 description 1
- 229960002048 guanfacine Drugs 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- KKLGDUSGQMHBPB-UHFFFAOYSA-N hex-2-ynedioic acid Chemical class OC(=O)CCC#CC(O)=O KKLGDUSGQMHBPB-UHFFFAOYSA-N 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 229940120120 innopran Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 229960004427 isradipine Drugs 0.000 description 1
- 229960001632 labetalol Drugs 0.000 description 1
- GKQPCPXONLDCMU-CCEZHUSRSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C GKQPCPXONLDCMU-CCEZHUSRSA-N 0.000 description 1
- 229960004340 lacidipine Drugs 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940041476 lactose 100 mg Drugs 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 229960004438 mibefradil Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- 230000037257 muscle growth Effects 0.000 description 1
- LRYFQZBTUIVNRC-UHFFFAOYSA-N n-methyl-n-(2,2,2-trifluoroethyl)aniline Chemical compound FC(F)(F)CN(C)C1=CC=CC=C1 LRYFQZBTUIVNRC-UHFFFAOYSA-N 0.000 description 1
- 229960004255 nadolol Drugs 0.000 description 1
- VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 229960000619 nebivolol Drugs 0.000 description 1
- 230000002644 neurohormonal effect Effects 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- VZWXXKDFACOXNT-UHFFFAOYSA-N niludipine Chemical compound CCCOCCOC(=O)C1=C(C)NC(C)=C(C(=O)OCCOCCC)C1C1=CC=CC([N+]([O-])=O)=C1 VZWXXKDFACOXNT-UHFFFAOYSA-N 0.000 description 1
- 229950000109 niludipine Drugs 0.000 description 1
- 229960005366 nilvadipine Drugs 0.000 description 1
- 229960000227 nisoldipine Drugs 0.000 description 1
- 229960005425 nitrendipine Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000005181 nitrobenzenes Chemical class 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 125000002347 octyl 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])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229960005117 olmesartan Drugs 0.000 description 1
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 1
- LVRLSYPNFFBYCZ-VGWMRTNUSA-N omapatrilat Chemical compound C([C@H](S)C(=O)N[C@H]1CCS[C@H]2CCC[C@H](N2C1=O)C(=O)O)C1=CC=CC=C1 LVRLSYPNFFBYCZ-VGWMRTNUSA-N 0.000 description 1
- 229950000973 omapatrilat Drugs 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960004570 oxprenolol Drugs 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229960002035 penbutolol Drugs 0.000 description 1
- KQXKVJAGOJTNJS-HNNXBMFYSA-N penbutolol Chemical compound CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1 KQXKVJAGOJTNJS-HNNXBMFYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229960002582 perindopril Drugs 0.000 description 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
- 230000036513 peripheral conductance Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 229960001989 prenylamine Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 230000036593 pulmonary vascular resistance Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- FLSLEGPOVLMJMN-YSSFQJQWSA-N quinaprilat Chemical compound C([C@H](N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)C(O)=O)CC1=CC=CC=C1 FLSLEGPOVLMJMN-YSSFQJQWSA-N 0.000 description 1
- 229960001007 quinaprilat Drugs 0.000 description 1
- VBUBADWLHFZFDK-UHFFFAOYSA-N quinazoline;hydrochloride Chemical compound Cl.N1=CN=CC2=CC=CC=C21 VBUBADWLHFZFDK-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- KEDYTOTWMPBSLG-HILJTLORSA-N ramiprilat Chemical compound C([C@H](N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)C(O)=O)CC1=CC=CC=C1 KEDYTOTWMPBSLG-HILJTLORSA-N 0.000 description 1
- 229960002231 ramiprilat Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 210000002235 sarcomere Anatomy 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229960002370 sotalol Drugs 0.000 description 1
- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 229960002909 spirapril Drugs 0.000 description 1
- HRWCVUIFMSZDJS-SZMVWBNQSA-N spirapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCS2)C(O)=O)CC1=CC=CC=C1 HRWCVUIFMSZDJS-SZMVWBNQSA-N 0.000 description 1
- 108700035424 spirapril Proteins 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 229960000651 tasosartan Drugs 0.000 description 1
- ADXGNEYLLLSOAR-UHFFFAOYSA-N tasosartan Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ADXGNEYLLLSOAR-UHFFFAOYSA-N 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- 229960004084 temocapril Drugs 0.000 description 1
- FIQOFIRCTOWDOW-BJLQDIEVSA-N temocapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C[C@H](SC1)C=1SC=CC=1)=O)CC1=CC=CC=C1 FIQOFIRCTOWDOW-BJLQDIEVSA-N 0.000 description 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229950003137 tiapamil Drugs 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960002051 trandolapril Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- BAVYZALUXZFZLV-FIBGUPNXSA-N trideuteriomethanamine Chemical compound [2H]C([2H])([2H])N BAVYZALUXZFZLV-FIBGUPNXSA-N 0.000 description 1
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- ACWBQPMHZXGDFX-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
- 229960002769 zofenopril Drugs 0.000 description 1
- IAIDUHCBNLFXEF-MNEFBYGVSA-N zofenopril Chemical compound C([C@@H](C)C(=O)N1[C@@H](C[C@@H](C1)SC=1C=CC=CC=1)C(O)=O)SC(=O)C1=CC=CC=C1 IAIDUHCBNLFXEF-MNEFBYGVSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
-
- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25764609P | 2009-11-03 | 2009-11-03 | |
| US61/257,646 | 2009-11-03 | ||
| PCT/US2010/054927 WO2011056740A1 (en) | 2009-11-03 | 2010-11-01 | Quinazoline compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2779989A1 true CA2779989A1 (en) | 2011-05-12 |
Family
ID=43970282
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2779989A Abandoned CA2779989A1 (en) | 2009-11-03 | 2010-11-01 | Quinazoline compounds |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8859571B2 (https=) |
| EP (1) | EP2501233B1 (https=) |
| JP (1) | JP5836963B2 (https=) |
| KR (1) | KR101736521B1 (https=) |
| CN (1) | CN102711474B (https=) |
| AU (1) | AU2010315361B2 (https=) |
| BR (1) | BR112012010524A2 (https=) |
| CA (1) | CA2779989A1 (https=) |
| EA (1) | EA021439B1 (https=) |
| ES (1) | ES2523465T3 (https=) |
| IL (1) | IL219504A (https=) |
| MX (1) | MX2012005155A (https=) |
| WO (1) | WO2011056740A1 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5603883B2 (ja) * | 2009-02-17 | 2014-10-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｂ−Ｒａｆキナーゼを阻害するためのピリミドピリミジン誘導体 |
| CN103159685A (zh) * | 2013-04-11 | 2013-06-19 | 苏州立新制药有限公司 | 4-氯-6，7-二(2-甲氧基乙氧基)喹唑啉的制备方法 |
| JP6527513B2 (ja) * | 2013-11-20 | 2019-06-05 | シグナルケム・ライフサイエンシーズ・コーポレイションＳｉｇｎａｌｃｈｅｍ Ｌｉｆｅｓｃｉｅｎｃｅｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｔａｍファミリーキナーゼ阻害剤としてのキナゾリン誘導体 |
| CN105849044B (zh) | 2013-12-26 | 2018-10-26 | 埃克森美孚研究工程公司 | Zsm-48晶体的合成 |
| CN111868039A (zh) * | 2017-09-26 | 2020-10-30 | 加利福尼亚大学董事会 | 用于治疗癌症的组合物和方法 |
| JP7785663B2 (ja) | 2019-09-16 | 2025-12-15 | ノバルティス アーゲー | 二機能性分解誘導薬及びそれらの使用方法 |
| WO2023049312A1 (en) | 2021-09-23 | 2023-03-30 | Erasca, Inc. | Egfr inhibitor polymorph forms |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9508565D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
| PT2213661E (pt) | 2003-09-26 | 2011-12-15 | Exelixis Inc | Moduladores de c-met e métodos de uso |
| CN103626742B (zh) * | 2005-11-01 | 2017-04-26 | 塔格根公司 | 激酶的联-芳基间-嘧啶抑制剂 |
-
2010
- 2010-11-01 AU AU2010315361A patent/AU2010315361B2/en not_active Ceased
- 2010-11-01 JP JP2012537925A patent/JP5836963B2/ja not_active Expired - Fee Related
- 2010-11-01 ES ES10828947.1T patent/ES2523465T3/es active Active
- 2010-11-01 KR KR1020127014231A patent/KR101736521B1/ko not_active Expired - Fee Related
- 2010-11-01 CN CN201080060451.4A patent/CN102711474B/zh not_active Expired - Fee Related
- 2010-11-01 EA EA201290243A patent/EA021439B1/ru not_active IP Right Cessation
- 2010-11-01 CA CA2779989A patent/CA2779989A1/en not_active Abandoned
- 2010-11-01 BR BR112012010524A patent/BR112012010524A2/pt not_active IP Right Cessation
- 2010-11-01 EP EP10828947.1A patent/EP2501233B1/en active Active
- 2010-11-01 US US13/505,324 patent/US8859571B2/en not_active Expired - Fee Related
- 2010-11-01 MX MX2012005155A patent/MX2012005155A/es active IP Right Grant
- 2010-11-01 WO PCT/US2010/054927 patent/WO2011056740A1/en not_active Ceased
-
2012
- 2012-04-30 IL IL219504A patent/IL219504A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| ES2523465T3 (es) | 2014-11-26 |
| US8859571B2 (en) | 2014-10-14 |
| JP2013510155A (ja) | 2013-03-21 |
| JP5836963B2 (ja) | 2015-12-24 |
| US20120220588A1 (en) | 2012-08-30 |
| EP2501233A1 (en) | 2012-09-26 |
| EA201290243A1 (ru) | 2012-12-28 |
| KR101736521B1 (ko) | 2017-05-16 |
| CN102711474A (zh) | 2012-10-03 |
| IL219504A (en) | 2016-09-29 |
| BR112012010524A2 (pt) | 2017-12-12 |
| KR20120112441A (ko) | 2012-10-11 |
| EP2501233B1 (en) | 2014-09-24 |
| WO2011056740A1 (en) | 2011-05-12 |
| MX2012005155A (es) | 2012-08-31 |
| CN102711474B (zh) | 2014-09-10 |
| AU2010315361A1 (en) | 2012-05-24 |
| AU2010315361B2 (en) | 2014-06-12 |
| EA021439B1 (ru) | 2015-06-30 |
| IL219504A0 (en) | 2012-06-28 |
| EP2501233A4 (en) | 2013-06-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2011205485B2 (en) | Compounds and methods | |
| ES2579830T3 (es) | Derivados de diaminopirimidina y procedimientos para la preparación de los mismos | |
| JP6117816B2 (ja) | Ｌｒｒｋ２モジュレーターとしてのアミノピリミジン誘導体 | |
| JP6180426B2 (ja) | パーキンソン病の処置のためのキナーゼｌｒｒｋ２モジュレーターとしての２−（フェニル又はピリド−３−イル）アミノピリミジン誘導体 | |
| AU2022217353B2 (en) | Pyridopyrimidinone derivative, preparation method therefor, and use thereof | |
| AU2010315361B2 (en) | Quinazoline compounds | |
| GB2281072A (en) | Angiotensin II receptor blocking imidazoline derivatives | |
| RS57332B1 (sr) | Heterociklični amidi kao inhibitori kinaze | |
| AU2005286592A1 (en) | Novel pyrimidine compounds, process for their preparation and compositions containing them | |
| ES2936481T3 (es) | 1H-Indazol-carboxamidas como inhibidores de la proteína cinasa 1 que interactúa con el receptor (RIPK1) | |
| KR101920472B1 (ko) | 오렉신 수용체 길항제로서의 피페리딘 유도체 | |
| WO2011056739A1 (en) | Compounds and methods | |
| CA3201054A1 (en) | Novel compounds as androgen receptor and phosphodiesterase dual inhibitor | |
| US20120157482A1 (en) | Compounds and methods | |
| DK2832728T3 (en) | TRIAZINONE CONNECTION AND TYPE OF T-CALCIUM CHANNEL INHIBITORS | |
| ES2665995T3 (es) | Imidazoles sustituidos como bloqueadores de canales de calcio de tipo N | |
| WO2011088031A1 (en) | Compounds and methods | |
| HK1195058A (en) | Aminopyrimidine derivatives as lrrk2 modulators | |
| HK1195301A (en) | Aminopyrimidine derivatives as lrrk2 modulators | |
| HK1195301B (en) | Aminopyrimidine derivatives as lrrk2 modulators |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20150916 |
|
| FZDE | Discontinued |
Effective date: 20190517 |