JP4031363B2 - α−1A/Bアドレナリン作動性受容体拮抗薬としてのキナゾロン誘導体 - Google Patents
α−1A/Bアドレナリン作動性受容体拮抗薬としてのキナゾロン誘導体 Download PDFInfo
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- JP4031363B2 JP4031363B2 JP2002554677A JP2002554677A JP4031363B2 JP 4031363 B2 JP4031363 B2 JP 4031363B2 JP 2002554677 A JP2002554677 A JP 2002554677A JP 2002554677 A JP2002554677 A JP 2002554677A JP 4031363 B2 JP4031363 B2 JP 4031363B2
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- Prior art keywords
- dimethoxy
- dihydro
- quinazolin
- group
- lower 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.)
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- 239000000674 adrenergic antagonist Substances 0.000 title description 13
- 150000001875 compounds Chemical class 0.000 claims description 253
- -1 methylenedioxy Chemical group 0.000 claims description 120
- 125000000217 alkyl group Chemical group 0.000 claims description 99
- 125000003545 alkoxy group Chemical group 0.000 claims description 71
- 125000003118 aryl group Chemical group 0.000 claims description 66
- 239000000203 mixture Substances 0.000 claims description 66
- 229910052736 halogen Inorganic materials 0.000 claims description 53
- 239000001257 hydrogen Substances 0.000 claims description 53
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 150000002367 halogens Chemical class 0.000 claims description 52
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 50
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
- 125000001424 substituent group Chemical group 0.000 claims description 42
- 150000002431 hydrogen Chemical class 0.000 claims description 40
- 229910052757 nitrogen Chemical group 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- 208000024891 symptom Diseases 0.000 claims description 35
- 229910052799 carbon Inorganic materials 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 29
- 125000004414 alkyl thio group Chemical group 0.000 claims description 28
- 125000001188 haloalkyl group Chemical group 0.000 claims description 27
- 125000005842 heteroatom Chemical group 0.000 claims description 27
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 24
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 24
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 23
- 125000004429 atom Chemical group 0.000 claims description 23
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 20
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 20
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 20
- 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 20
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 20
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
- 125000003282 alkyl amino group Chemical group 0.000 claims description 19
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 19
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 18
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 17
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 15
- 239000000651 prodrug Substances 0.000 claims description 14
- 229940002612 prodrug Drugs 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 10
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 208000014001 urinary system disease Diseases 0.000 claims description 8
- KGCAQIWQLMNEJR-UHFFFAOYSA-N 6,7-dimethoxy-2-[5-(morpholin-4-ylmethyl)-3,4-dihydro-1h-isoquinolin-2-yl]-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(CC1=CC=C2)CCC1=C2CN1CCOCC1 KGCAQIWQLMNEJR-UHFFFAOYSA-N 0.000 claims description 7
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 7
- ZZRHPMVACJGNBF-UHFFFAOYSA-N 3-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)-6,7-dimethoxy-4h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound COC1=C(OC)C=C2S(=O)(=O)NC(N3CCC=4C=C(C(=CC=4C3)OC)OC)=NC2=C1 ZZRHPMVACJGNBF-UHFFFAOYSA-N 0.000 claims description 6
- 208000026723 Urinary tract disease Diseases 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- MYYKTZCWELANAY-UHFFFAOYSA-N 2-(3,4-dihydro-1h-pyrido[4,3-b][1,6]naphthyridin-2-yl)-6,7-dimethoxy-1h-quinazolin-4-one Chemical compound C1=NC=C2C=C(CN(C=3NC=4C=C(C(=CC=4C(=O)N=3)OC)OC)CC3)C3=NC2=C1 MYYKTZCWELANAY-UHFFFAOYSA-N 0.000 claims description 5
- NWWDMEBFEXNAQY-UHFFFAOYSA-N 2-(3-cyclohexyl-3,5,6,7-tetrahydroimidazo[1,5-a]pyrazin-6-yl)-6,7-dimethoxy-3H-quinazolin-4-one Chemical compound COC1=C(C=C2C(=C1)C(=O)NC(=N2)C3CN4C(N=CC4=CN3)C5CCCCC5)OC NWWDMEBFEXNAQY-UHFFFAOYSA-N 0.000 claims description 5
- AYTNQBBFZGEZRO-UHFFFAOYSA-N 2-[1-(3-chlorophenyl)-6,7-dihydro-4h-imidazo[4,5-c]pyridin-5-yl]-6,7-dimethoxy-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1N=CN2C1=CC=CC(Cl)=C1 AYTNQBBFZGEZRO-UHFFFAOYSA-N 0.000 claims description 5
- XCHMRCYMRVDBSW-UHFFFAOYSA-N 2-[4-(benzylamino)-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-7-yl]-6,7-dimethoxy-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1N=CN=C2NCC1=CC=CC=C1 XCHMRCYMRVDBSW-UHFFFAOYSA-N 0.000 claims description 5
- BZSCPRDBSKPCNT-UHFFFAOYSA-N 6,7-dimethoxy-2-(1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl)-1h-quinazolin-4-one Chemical compound N1C2=CC=CC=C2C(CC2)=C1CN2C1=NC(C=C(C(=C2)OC)OC)=C2C(=O)N1 BZSCPRDBSKPCNT-UHFFFAOYSA-N 0.000 claims description 5
- NSMYFMQCZREYGB-UHFFFAOYSA-N 6,7-dimethoxy-2-(3-phenyl-3,5,6,7-tetrahydroimidazo[1,5-a]pyrazin-6-yl)-3H-quinazolin-4-one Chemical compound COC1=C(C=C2C(=C1)C(=O)NC(=N2)C3CN4C(N=CC4=CN3)C5=CC=CC=C5)OC NSMYFMQCZREYGB-UHFFFAOYSA-N 0.000 claims description 5
- UVPXAIPQNSGMNS-UHFFFAOYSA-N 6,7-dimethoxy-2-(5-morpholin-4-ylsulfonyl-3,4-dihydro-1h-isoquinolin-2-yl)-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1C=CC=C2S(=O)(=O)N1CCOCC1 UVPXAIPQNSGMNS-UHFFFAOYSA-N 0.000 claims description 5
- UAIZAGBMGMPSNL-UHFFFAOYSA-N 6,7-dimethoxy-2-(6-methoxy-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl)-1h-quinazolin-4-one Chemical compound COC1=C(OC)C=C2C(=O)NC(N3CC=4NC5=CC=C(C=C5C=4CC3)OC)=NC2=C1 UAIZAGBMGMPSNL-UHFFFAOYSA-N 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- CFKFKGSYZNAKOS-UHFFFAOYSA-N 2-(6,7-dimethoxy-4-oxo-1h-quinazolin-2-yl)-6,7-dimethoxy-3,4-dihydro-1h-isoquinoline-5-carbonitrile Chemical compound C1CC(C(=C(OC)C(OC)=C2)C#N)=C2CN1C1=NC(C=C(C(=C2)OC)OC)=C2C(=O)N1 CFKFKGSYZNAKOS-UHFFFAOYSA-N 0.000 claims description 4
- AFKCUFDGHUIKHL-UHFFFAOYSA-N 2-(6,7-dimethoxy-4-oxo-1h-quinazolin-2-yl)-n-(2-pyridin-2-ylethyl)-3,4-dihydro-1h-isoquinoline-7-sulfonamide Chemical compound N=1C(=O)C=2C=C(OC)C(OC)=CC=2NC=1N(CC1=C2)CCC1=CC=C2S(=O)(=O)NCCC1=CC=CC=N1 AFKCUFDGHUIKHL-UHFFFAOYSA-N 0.000 claims description 4
- NUVNTYDEDKGAPU-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)-6,7-dihydro-4h-imidazo[4,5-c]pyridin-5-yl]-6,7-dimethoxy-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1N=CN2C1=CC=C(Cl)C=C1 NUVNTYDEDKGAPU-UHFFFAOYSA-N 0.000 claims description 4
- QLTVPNPZNQEUJY-UHFFFAOYSA-N 2-[5-(1h-imidazol-2-yl)-3,4-dihydro-1h-isoquinolin-2-yl]-6,7-dimethoxy-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1C=CC=C2C1=NC=CN1 QLTVPNPZNQEUJY-UHFFFAOYSA-N 0.000 claims description 4
- FSAGFYQBPWGVMA-UHFFFAOYSA-N 2-[5-(4,5-dihydro-1h-imidazol-2-ylamino)-3,4-dihydro-1h-isoquinolin-2-yl]-6,7-dimethoxy-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1C=CC=C2NC1=NCCN1 FSAGFYQBPWGVMA-UHFFFAOYSA-N 0.000 claims description 4
- NCHIHXQFKMPELD-UHFFFAOYSA-N 6,7-dimethoxy-2-(1-naphthalen-2-yl-6,7-dihydro-4h-imidazo[4,5-c]pyridin-5-yl)-1h-quinazolin-4-one Chemical compound C1=CC=CC2=CC(N3C=NC4=C3CCN(C4)C3=NC=4C=C(C(=CC=4C(=O)N3)OC)OC)=CC=C21 NCHIHXQFKMPELD-UHFFFAOYSA-N 0.000 claims description 4
- ZXJDRUCKZNIUDB-UHFFFAOYSA-N 6,7-dimethoxy-2-(1-phenyl-6,7-dihydro-4h-imidazo[4,5-c]pyridin-5-yl)-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1N=CN2C1=CC=CC=C1 ZXJDRUCKZNIUDB-UHFFFAOYSA-N 0.000 claims description 4
- XUGNZQMRYTVJRN-UHFFFAOYSA-N 6,7-dimethoxy-2-(4-morpholin-4-yl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-7-yl)-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1N=CN=C2N1CCOCC1 XUGNZQMRYTVJRN-UHFFFAOYSA-N 0.000 claims description 4
- BKTPWLOJLYJMJI-UHFFFAOYSA-N 6,7-dimethoxy-2-(4-piperidin-1-yl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-7-yl)-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1N=CN=C2N1CCCCC1 BKTPWLOJLYJMJI-UHFFFAOYSA-N 0.000 claims description 4
- JQOSCBFBHIQXRR-UHFFFAOYSA-N 6,7-dimethoxy-2-(5-pyridin-4-yl-3,4-dihydro-1h-isoquinolin-2-yl)-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1C=CC=C2C1=CC=NC=C1 JQOSCBFBHIQXRR-UHFFFAOYSA-N 0.000 claims description 4
- ZSKWVHWKJVIBTJ-UHFFFAOYSA-N 6,7-dimethoxy-2-(5-pyrimidin-5-yl-3,4-dihydro-1h-isoquinolin-2-yl)-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1C=CC=C2C1=CN=CN=C1 ZSKWVHWKJVIBTJ-UHFFFAOYSA-N 0.000 claims description 4
- NONNATLFKKPMCH-UHFFFAOYSA-N 6,7-dimethoxy-2-(5-pyrrolidin-1-yl-3,4-dihydro-1h-isoquinolin-2-yl)-1h-quinazolin-4-one Chemical compound N1C(=O)C=2C=C(OC)C(OC)=CC=2N=C1N(C1)CCC2=C1C=CC=C2N1CCCC1 NONNATLFKKPMCH-UHFFFAOYSA-N 0.000 claims description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- 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
- C07D405/14—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 three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
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- Rheumatology (AREA)
- Neurosurgery (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
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| US32526701P | 2001-09-27 | 2001-09-27 | |
| PCT/EP2001/014885 WO2002053558A1 (en) | 2001-01-02 | 2001-12-17 | Quinazolone derivatives as alpha 1a/b adrenergic receptor antagonists |
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| JP2004519454A JP2004519454A (ja) | 2004-07-02 |
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| GB0225908D0 (en) * | 2002-11-06 | 2002-12-11 | Pfizer Ltd | Treatment of female sexual dysfunction |
| WO2005005397A1 (en) * | 2003-07-02 | 2005-01-20 | F. Hoffmann-La Roche Ag | 5-substituted quinazolinone derivatives |
| JP2009513502A (ja) * | 2003-07-02 | 2009-04-02 | エフ.ホフマン−ラ ロシュ アーゲー | アリールアミン置換キナゾリノン化合物 |
| TW200530235A (en) | 2003-12-24 | 2005-09-16 | Renovis Inc | Bicycloheteroarylamine compounds as ion channel ligands and uses thereof |
| US7793137B2 (en) | 2004-10-07 | 2010-09-07 | Cisco Technology, Inc. | Redundant power and data in a wired data telecommunincations network |
| FR2870846B1 (fr) | 2004-05-25 | 2006-08-04 | Sanofi Synthelabo | Derives de tetrahydroisoquinolylsulfonamides, leur preparation et leur utilisation en therapeutique |
| US20060128710A1 (en) * | 2004-12-09 | 2006-06-15 | Chih-Hung Lee | Antagonists to the vanilloid receptor subtype 1 (VR1) and uses thereof |
| US7297700B2 (en) | 2005-03-24 | 2007-11-20 | Renovis, Inc. | Bicycloheteroaryl compounds as P2X7 modulators and uses thereof |
| WO2006119504A2 (en) | 2005-05-04 | 2006-11-09 | Renovis, Inc. | Fused heterocyclic compounds, and compositions and uses thereof |
| US7709468B2 (en) | 2005-09-02 | 2010-05-04 | Abbott Laboratories | Imidazo based heterocycles |
| EP1956001A4 (en) * | 2005-11-24 | 2012-12-26 | Kissei Pharmaceutical | PHARMACEUTICAL PRODUCT FOR USE IN THE TREATMENT OF URETEROLITHIASE |
| CA2682162C (en) | 2007-04-02 | 2016-05-10 | Renovis, Inc. | Pyrid-2-yl fused heterocyclic compounds, and compositions and uses thereof |
| PL2139334T3 (pl) | 2007-04-17 | 2013-11-29 | Evotec Ag | Skondensowane związki heterocykliczne 2-cyjanofenylu i ich kompozycje i zastosowania |
| US8859538B2 (en) | 2007-06-21 | 2014-10-14 | Cara Therapeutics, Inc. | Uses of substituted imidazoheterocycles |
| EA201000046A1 (ru) | 2007-06-21 | 2011-02-28 | Кара Терапеутикс, Инк. | Замещенные имидазогетероциклы |
| CN101417999A (zh) * | 2007-10-25 | 2009-04-29 | 上海恒瑞医药有限公司 | 哌嗪类衍生物,其制备方法及其在医药上的应用 |
| JO3156B1 (ar) | 2009-07-09 | 2017-09-20 | Novartis Ag | ايميدازولات مدمجة والتركيبات التي تشملها لعلاج الأمراض الطفيلية على مثال الملاريا |
| WO2015018797A2 (en) * | 2013-08-05 | 2015-02-12 | Haplogen Gmbh | Antiviral compounds |
| GB201321748D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| SG11201604878XA (en) * | 2013-12-20 | 2016-07-28 | Esteve Labor Dr | Fused imidazolyl derivatives, their preparation and use as medicaments |
| AU2017266911B2 (en) | 2016-05-18 | 2021-09-02 | Array Biopharma, Inc. | KRas G12C inhibitors |
| CN107434786B (zh) * | 2016-05-27 | 2025-11-18 | 广东东阳光药业股份有限公司 | 苯并咪唑化合物及其制备方法 |
| TWI791515B (zh) | 2017-04-24 | 2023-02-11 | 瑞士商諾華公司 | 治療療法 |
| SI3710439T1 (sl) | 2017-11-15 | 2023-06-30 | Mirati Therapeutics, Inc., | Zaviralci mutacije kras g12c |
| US10647715B2 (en) | 2017-11-15 | 2020-05-12 | Mirati Therapeutics, Inc. | KRas G12C inhibitors |
| WO2019217307A1 (en) | 2018-05-07 | 2019-11-14 | Mirati Therapeutics, Inc. | Kras g12c inhibitors |
| EP3849538A4 (en) | 2018-09-10 | 2022-06-29 | Mirati Therapeutics, Inc. | Combination therapies |
| EP3849536A4 (en) | 2018-09-10 | 2022-06-29 | Mirati Therapeutics, Inc. | Combination therapies |
| HRP20250059T1 (hr) | 2018-09-10 | 2025-03-28 | Mirati Therapeutics, Inc. | Kombinirane terapije |
| EA202190630A1 (ru) | 2018-12-05 | 2021-10-11 | Мирати Терапьютикс, Инк. | Способы комбинированной терапии |
| WO2020146613A1 (en) | 2019-01-10 | 2020-07-16 | Mirati Therapeutics, Inc. | Kras g12c inhibitors |
| KR20210146288A (ko) * | 2019-03-01 | 2021-12-03 | 레볼루션 메디슨즈, 인크. | 이환식 헤테로사이클릴 화합물 및 이의 용도 |
| JP7622043B2 (ja) | 2019-08-29 | 2025-01-27 | ミラティ セラピューティクス, インコーポレイテッド | Kras g12d阻害剤 |
| CA3152025A1 (en) | 2019-09-24 | 2021-04-01 | David BRIERE | Combination therapies |
| CN110950886A (zh) * | 2019-12-13 | 2020-04-03 | 苏州莱克施德药业有限公司 | 一种合成1-甲基-咪唑-2-甲酸甲酯衍生物的方法 |
| EP4076418A4 (en) | 2019-12-20 | 2024-01-24 | Mirati Therapeutics, Inc. | Sos1 inhibitors |
| JP2023540809A (ja) | 2020-09-11 | 2023-09-26 | ミラティ セラピューティクス, インコーポレイテッド | Kras g12c阻害剤の結晶形態 |
| IL303446A (en) | 2020-12-15 | 2023-08-01 | Mirati Therapeutics Inc | Azaquinazoline compounds as PAN-KRas inhibitors |
| WO2022133038A1 (en) | 2020-12-16 | 2022-06-23 | Mirati Therapeutics, Inc. | Tetrahydropyridopyrimidine pan-kras inhibitors |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1062357A (en) * | 1965-03-23 | 1967-03-22 | Pfizer & Co C | Quinazolone derivatives |
| US4044136A (en) * | 1972-09-09 | 1977-08-23 | Pfizer Inc. | Aminoquinazoline therapeutic agents |
| DE2757925A1 (de) * | 1977-12-24 | 1979-06-28 | Bayer Ag | Diazacyclo-1.2.4-benzothiadizine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| NZ325248A (en) * | 1995-12-23 | 1999-09-29 | Pfizer Res & Dev | Quinoline and quinazoline compounds useful in therapy |
| GB9700504D0 (en) * | 1997-01-11 | 1997-02-26 | Pfizer Ltd | Pharmaceutical compounds |
| WO2000055143A1 (en) * | 1999-03-17 | 2000-09-21 | F. Hoffmann-La Roche Ag | Oxazolone derivatives and their use as alpha-1 adrenoreceptor modulators |
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2001
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- 2001-12-17 WO PCT/EP2001/014885 patent/WO2002053558A1/en not_active Ceased
- 2001-12-17 ES ES01985417T patent/ES2241891T3/es not_active Expired - Lifetime
- 2001-12-17 KR KR1020037008921A patent/KR100554813B1/ko not_active Expired - Fee Related
- 2001-12-17 BR BR0116662-0A patent/BR0116662A/pt not_active IP Right Cessation
- 2001-12-17 AT AT01985417T patent/ATE295362T1/de not_active IP Right Cessation
- 2001-12-27 PE PE2001001308A patent/PE20020735A1/es not_active Application Discontinuation
- 2001-12-27 PA PA20018536001A patent/PA8536001A1/es unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| PA8536001A1 (es) | 2002-08-29 |
| KR100554813B1 (ko) | 2006-02-22 |
| ATE295362T1 (de) | 2005-05-15 |
| ZA200305038B (en) | 2004-09-27 |
| CN1484640A (zh) | 2004-03-24 |
| DE60110844T2 (de) | 2006-01-12 |
| CA2432578A1 (en) | 2002-07-11 |
| KR20030063490A (ko) | 2003-07-28 |
| DE60110844D1 (de) | 2005-06-16 |
| CN1237060C (zh) | 2006-01-18 |
| EP1363899B1 (en) | 2005-05-11 |
| MXPA03005854A (es) | 2003-09-10 |
| ES2241891T3 (es) | 2005-11-01 |
| AR035775A1 (es) | 2004-07-14 |
| JP2004519454A (ja) | 2004-07-02 |
| PE20020735A1 (es) | 2002-08-21 |
| UY27109A1 (es) | 2002-07-31 |
| BR0116662A (pt) | 2003-09-23 |
| EP1363899A1 (en) | 2003-11-26 |
| CA2432578C (en) | 2008-04-01 |
| WO2002053558A1 (en) | 2002-07-11 |
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