JP5836963B2 - キナゾリン化合物 - Google Patents
キナゾリン化合物 Download PDFInfo
- Publication number
- JP5836963B2 JP5836963B2 JP2012537925A JP2012537925A JP5836963B2 JP 5836963 B2 JP5836963 B2 JP 5836963B2 JP 2012537925 A JP2012537925 A JP 2012537925A JP 2012537925 A JP2012537925 A JP 2012537925A JP 5836963 B2 JP5836963 B2 JP 5836963B2
- Authority
- JP
- Japan
- 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.)
- Expired - Fee Related
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- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 155
- -1 nitro, amino Chemical group 0.000 claims description 133
- 150000001875 compounds Chemical class 0.000 claims description 115
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 97
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 89
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 57
- 229910052736 halogen Inorganic materials 0.000 claims description 54
- 150000002367 halogens Chemical class 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 50
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 26
- 206010019280 Heart failures Diseases 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 22
- 229910052717 sulfur Chemical group 0.000 claims description 22
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 21
- 125000003282 alkyl amino group Chemical group 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 125000005842 heteroatom 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
- 239000007983 Tris buffer Substances 0.000 claims description 15
- 239000001301 oxygen Chemical group 0.000 claims description 15
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 14
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 239000011593 sulfur Chemical group 0.000 claims description 13
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 12
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
- 101000662993 Homo sapiens Serine/threonine-protein kinase TNNI3K Proteins 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 9
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000001412 tetrahydropyranyl 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
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 7
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 6
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 6
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 6
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 6
- 125000006771 (C1-C6) haloalkylthio group Chemical group 0.000 claims description 6
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 5
- 125000006648 (C1-C8) haloalkyl group Chemical group 0.000 claims description 5
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 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
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 5
- 125000005843 halogen 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 4
- 102100037670 Serine/threonine-protein kinase TNNI3K Human genes 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 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 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 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
- 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 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
- 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
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 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
- 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
- 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 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
- 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
- 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 claims description 2
- 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 description 2
- 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 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
- 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 description 2
- 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 description 2
- 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 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
- 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
- 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 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
- 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
- AWOZBPUJLRHKQY-UHFFFAOYSA-N 4-chloro-3-[(5,7-dimethoxyquinazolin-4-yl)amino]-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Cl)C(NC=2C3=C(OC)C=C(OC)C=C3N=CN=2)=C1 AWOZBPUJLRHKQY-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
- LCFPGSGLOPXSJD-UHFFFAOYSA-N 5-[(6,7-dimethoxyquinazolin-4-yl)amino]-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)=C1 LCFPGSGLOPXSJD-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
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 1
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- 239000000203 mixture Substances 0.000 description 75
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- 239000007787 solid Substances 0.000 description 57
- 238000000034 method Methods 0.000 description 41
- 239000000243 solution Substances 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
- 238000004519 manufacturing process Methods 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 125000001072 heteroaryl group Chemical group 0.000 description 14
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 13
- 229940108485 tenormin Drugs 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 239000012267 brine Substances 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 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 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
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- 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
- 229960002256 spironolactone Drugs 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
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003460 sulfonic acids 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
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 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
- 229940095064 tartrate Drugs 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940083085 thiazide derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 210000001519 tissue Anatomy 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
- 229960004699 valsartan Drugs 0.000 description 1
- SJSNUMAYCRRIOM-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=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229940063670 visken Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
- 239000011701 zinc Substances 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 (3)
| Publication Number | Publication Date |
|---|---|
| JP2013510155A JP2013510155A (ja) | 2013-03-21 |
| JP2013510155A5 JP2013510155A5 (https=) | 2013-12-19 |
| JP5836963B2 true JP5836963B2 (ja) | 2015-12-24 |
Family
ID=43970282
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012537925A Expired - Fee Related JP5836963B2 (ja) | 2009-11-03 | 2010-11-01 | キナゾリン化合物 |
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 |
| CA2779989A1 (en) | 2011-05-12 |
| 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 |
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