JP2008514703A - 置換２ｈ−１，３−ベンゾオキサジン−４（３ｈ）−オン - Google Patents
置換２ｈ−１，３−ベンゾオキサジン−４（３ｈ）−オン Download PDFInfo
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- JP2008514703A JP2008514703A JP2007534673A JP2007534673A JP2008514703A JP 2008514703 A JP2008514703 A JP 2008514703A JP 2007534673 A JP2007534673 A JP 2007534673A JP 2007534673 A JP2007534673 A JP 2007534673A JP 2008514703 A JP2008514703 A JP 2008514703A
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- Prior art keywords
- alkyl
- group
- cycloalkyl
- compound
- alkoxy
- Prior art date
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- YBYIZRPBXCCDQW-UHFFFAOYSA-N 2,3-dihydro-1,3-benzoxazin-4-one Chemical class C1=CC=C2C(=O)NCOC2=C1 YBYIZRPBXCCDQW-UHFFFAOYSA-N 0.000 title 1
- 108010085249 Purinergic P2 Receptors Proteins 0.000 abstract description 16
- 208000007536 Thrombosis Diseases 0.000 abstract description 13
- 238000011282 treatment Methods 0.000 abstract description 12
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 6
- 230000002785 anti-thrombosis Effects 0.000 abstract description 6
- 239000003112 inhibitor Substances 0.000 abstract description 6
- 230000002265 prevention Effects 0.000 abstract description 6
- 230000000302 ischemic effect Effects 0.000 abstract description 5
- 230000001732 thrombotic effect Effects 0.000 abstract description 5
- 102000007466 Purinergic P2 Receptors Human genes 0.000 abstract 3
- PYPGAMUVJIIXGC-UHFFFAOYSA-N 2,3-dihydro-1,2-benzoxazin-4-one Chemical class C1=CC=C2C(=O)CNOC2=C1 PYPGAMUVJIIXGC-UHFFFAOYSA-N 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 98
- -1 triazolo [4,5-d] pyrimidine compound Chemical class 0.000 description 77
- 238000000034 method Methods 0.000 description 76
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 125000000217 alkyl group Chemical group 0.000 description 38
- 239000000243 solution Substances 0.000 description 27
- 239000000203 mixture Substances 0.000 description 24
- 229940100389 Sulfonylurea Drugs 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 22
- 239000008194 pharmaceutical composition Substances 0.000 description 22
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 22
- 238000010168 coupling process Methods 0.000 description 20
- 150000003839 salts Chemical class 0.000 description 20
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 230000008878 coupling Effects 0.000 description 18
- 238000005859 coupling reaction Methods 0.000 description 18
- 229910052739 hydrogen Inorganic materials 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 229910052799 carbon Inorganic materials 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 229930040373 Paraformaldehyde Natural products 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 229920002866 paraformaldehyde Polymers 0.000 description 14
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 13
- 102100037600 P2Y purinoceptor 1 Human genes 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229910052736 halogen Inorganic materials 0.000 description 12
- 150000002367 halogens Chemical class 0.000 description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 12
- 125000003545 alkoxy group Chemical group 0.000 description 11
- 125000003282 alkyl amino group Chemical group 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 238000007363 ring formation reaction Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- VTNGEMDEEHFJLF-UHFFFAOYSA-N 6-fluoro-7-(methylamino)-2,3-dihydro-1,3-benzoxazin-4-one Chemical compound O1CNC(=O)C2=C1C=C(NC)C(F)=C2 VTNGEMDEEHFJLF-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000027455 binding Effects 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000004007 reversed phase HPLC Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 9
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 8
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 8
- WLMZTKAZJUWXCB-KQYNXXCUSA-N [(2r,3s,4r,5r)-5-(6-amino-2-methylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate Chemical compound C12=NC(SC)=NC(N)=C2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O WLMZTKAZJUWXCB-KQYNXXCUSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- NEOFAAAZQLBBKD-UHFFFAOYSA-N 3-(4-aminophenyl)-6-fluoro-7-(methylamino)-2h-1,3-benzoxazin-4-one Chemical compound O=C1C=2C=C(F)C(NC)=CC=2OCN1C1=CC=C(N)C=C1 NEOFAAAZQLBBKD-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- ZQSGTPNEPXTXCG-UHFFFAOYSA-N [F].CN Chemical group [F].CN ZQSGTPNEPXTXCG-UHFFFAOYSA-N 0.000 description 7
- 230000002776 aggregation Effects 0.000 description 7
- 238000004220 aggregation Methods 0.000 description 7
- 239000003146 anticoagulant agent Substances 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- TZBHPYXJOJGKDT-UHFFFAOYSA-N 1,3-oxazin-4-one Chemical compound O=C1C=COC=N1 TZBHPYXJOJGKDT-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- MZRHKDKHMUCYBN-UHFFFAOYSA-N 3-(6-aminopyridin-3-yl)-6-fluoro-7-(methylamino)-2h-1,3-benzoxazin-4-one Chemical compound O=C1C=2C=C(F)C(NC)=CC=2OCN1C1=CC=C(N)N=C1 MZRHKDKHMUCYBN-UHFFFAOYSA-N 0.000 description 5
- RKLQLYBJAZBSEU-UHFFFAOYSA-N 5-chlorothiophene-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC=C(Cl)S1 RKLQLYBJAZBSEU-UHFFFAOYSA-N 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- 210000004623 platelet-rich plasma Anatomy 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- ZICMXDTUWKRMPD-UHFFFAOYSA-N 3-(4-aminophenyl)-6-chloro-7-(methylamino)-2h-1,3-benzoxazin-4-one Chemical compound O=C1C=2C=C(Cl)C(NC)=CC=2OCN1C1=CC=C(N)C=C1 ZICMXDTUWKRMPD-UHFFFAOYSA-N 0.000 description 4
- KAKSTVYACPZRLL-UHFFFAOYSA-N 4,5-difluoro-2-hydroxy-n-[(4-methoxyphenyl)methyl]benzamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CC(F)=C(F)C=C1O KAKSTVYACPZRLL-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- 102000007347 Apyrase Human genes 0.000 description 4
- 108010007730 Apyrase Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 125000002393 azetidinyl group Chemical group 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 230000008034 disappearance Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- XALLJMFDLUYTTF-UHFFFAOYSA-N ethyl n-(5-chlorothiophen-2-yl)sulfonylcarbamate Chemical compound CCOC(=O)NS(=O)(=O)C1=CC=C(Cl)S1 XALLJMFDLUYTTF-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 229960000581 salicylamide Drugs 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 3
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 3
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 3
- QWNDEMKSHWFLRH-UHFFFAOYSA-N 3-(2-methoxyethoxy)-4-nitroaniline Chemical compound COCCOC1=CC(N)=CC=C1[N+]([O-])=O QWNDEMKSHWFLRH-UHFFFAOYSA-N 0.000 description 3
- SCTVEXUIFZIYSI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxy-n-(4-nitrophenyl)benzamide Chemical compound OC1=CC(F)=C(F)C=C1C(=O)NC1=CC=C([N+]([O-])=O)C=C1 SCTVEXUIFZIYSI-UHFFFAOYSA-N 0.000 description 3
- LQPQOESULBOBBB-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C=C1O LQPQOESULBOBBB-UHFFFAOYSA-N 0.000 description 3
- KIBQMIDIQJEPND-UHFFFAOYSA-N 4-[6-fluoro-7-(methylamino)-4-oxo-2h-1,3-benzoxazin-3-yl]benzoic acid Chemical compound O=C1C=2C=C(F)C(NC)=CC=2OCN1C1=CC=C(C(O)=O)C=C1 KIBQMIDIQJEPND-UHFFFAOYSA-N 0.000 description 3
- WGWLJYPEKXJWMS-UHFFFAOYSA-N 6,7-difluoro-3-(4-nitrophenyl)-2h-1,3-benzoxazin-4-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1C(=O)C2=CC(F)=C(F)C=C2OC1 WGWLJYPEKXJWMS-UHFFFAOYSA-N 0.000 description 3
- AKPSCZYOCGQJGX-UHFFFAOYSA-N 6,7-difluoro-3-[(4-methoxyphenyl)methyl]-2h-1,3-benzoxazin-4-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=CC(F)=C(F)C=C2OC1 AKPSCZYOCGQJGX-UHFFFAOYSA-N 0.000 description 3
- OHUBMXJEUSKSQA-UHFFFAOYSA-N 6-chloro-7-(methylamino)-3-(4-nitrophenyl)-2h-1,3-benzoxazin-4-one Chemical compound O=C1C=2C=C(Cl)C(NC)=CC=2OCN1C1=CC=C([N+]([O-])=O)C=C1 OHUBMXJEUSKSQA-UHFFFAOYSA-N 0.000 description 3
- WVDWLWBKBDDJEK-UHFFFAOYSA-N 6-chloro-7-fluoro-3-(4-nitrophenyl)-2h-1,3-benzoxazin-4-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1C(=O)C2=CC(Cl)=C(F)C=C2OC1 WVDWLWBKBDDJEK-UHFFFAOYSA-N 0.000 description 3
- RERULFNMEFZESK-UHFFFAOYSA-N 6-fluoro-3-[(4-methoxyphenyl)methyl]-7-(methylamino)-2h-1,3-benzoxazin-4-one Chemical compound O=C1C=2C=C(F)C(NC)=CC=2OCN1CC1=CC=C(OC)C=C1 RERULFNMEFZESK-UHFFFAOYSA-N 0.000 description 3
- FQTUTIOVHZCFCK-UHFFFAOYSA-N 6-fluoro-7-(methylamino)-3-(4-nitrophenyl)-2h-1,3-benzoxazin-4-one Chemical compound O=C1C=2C=C(F)C(NC)=CC=2OCN1C1=CC=C([N+]([O-])=O)C=C1 FQTUTIOVHZCFCK-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 3
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 3
- 206010002388 Angina unstable Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 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 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 208000007718 Stable Angina Diseases 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 208000007814 Unstable Angina Diseases 0.000 description 3
- 229960001456 adenosine triphosphate Drugs 0.000 description 3
- 150000001448 anilines Chemical class 0.000 description 3
- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 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
- 238000001816 cooling Methods 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61456404P | 2004-09-29 | 2004-09-29 | |
| PCT/US2005/034246 WO2006039212A2 (en) | 2004-09-29 | 2005-09-26 | Substituted 2h-1,3-benzoxazin-4(3h)-ones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008514703A true JP2008514703A (ja) | 2008-05-08 |
| JP2008514703A5 JP2008514703A5 (enExample) | 2008-09-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007534673A Ceased JP2008514703A (ja) | 2004-09-29 | 2005-09-26 | 置換２ｈ−１，３−ベンゾオキサジン−４（３ｈ）−オン |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US7205296B2 (enExample) |
| EP (1) | EP1812429A4 (enExample) |
| JP (1) | JP2008514703A (enExample) |
| KR (1) | KR20070064356A (enExample) |
| CN (1) | CN101031565B (enExample) |
| AU (1) | AU2005292314B2 (enExample) |
| BR (1) | BRPI0516181A (enExample) |
| CA (1) | CA2581638A1 (enExample) |
| IL (1) | IL182180A0 (enExample) |
| MX (1) | MX2007003836A (enExample) |
| NZ (1) | NZ554211A (enExample) |
| WO (1) | WO2006039212A2 (enExample) |
| ZA (1) | ZA200702688B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015518863A (ja) * | 2012-05-22 | 2015-07-06 | ジェネンテック， インコーポレイテッド | Ｎ−置換ベンズアミドおよび疼痛の処置におけるそれらの使用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7834023B2 (en) | 2006-09-20 | 2010-11-16 | Portola Pharmaceuticals, Inc. | Substituted dihydroquinazolines as platelet ADP receptor inhibitors |
| US7740693B2 (en) * | 2007-10-01 | 2010-06-22 | Honeywell International Inc. | Organic fluorescent sulfonyl ureido benzoxazinone pigments |
| CA2853439A1 (en) | 2011-10-31 | 2013-05-10 | Xenon Pharmaceuticals Inc. | Benzenesulfonamide compounds and their use as therapeutic agents |
| CA2855019A1 (en) | 2011-10-31 | 2013-05-10 | Xenon Pharmaceuticals Inc. | Biaryl ether sulfonamides and their use as therapeutic agents |
| BR112015000187A2 (pt) | 2012-07-06 | 2017-06-27 | Genentech Inc | benzamidas substituídas com n e métodos de uso das mesmas |
| HK1213181A1 (zh) | 2012-09-27 | 2016-06-30 | Portola Pharmaceuticals, Inc. | 雙環氧雜內酰胺激酶抑制劑 |
| BR112015022488A2 (pt) | 2013-03-14 | 2017-07-18 | Genentech Inc | triazolopiridinas substituídas e métodos de uso das mesmas |
| EP2970156B1 (en) | 2013-03-15 | 2018-07-25 | Genentech, Inc. | Substituted benzoxazoles and methods of use thereof |
| JP6383418B2 (ja) | 2013-11-27 | 2018-08-29 | ジェネンテック， インコーポレイテッド | 置換ベンズアミド及びその使用方法 |
| EP3166939B1 (en) | 2014-07-07 | 2019-06-05 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| KR102523430B1 (ko) | 2014-08-04 | 2023-04-19 | 누에볼루션 에이/에스 | 염증성, 대사성, 종양성 및 자가면역성 질환의 치료에 유용한 피리미딘의 임의적 융합 헤테로시클릴-치환 유도체 |
| RS60906B1 (sr) | 2014-10-06 | 2020-11-30 | Vertex Pharma | Modulatori regulatora transmembranske provodljivosti za cističnu fibrozu |
| PT3578547T (pt) | 2015-02-16 | 2021-06-22 | The Provost Fellows Found Scholars And Other Members Of Board Of College Of Holy And Undivided Trini | Sulfonilureias e compostos relacionados e uso dos mesmos |
| CR20170591A (es) | 2015-05-22 | 2018-05-07 | Genentech Inc | Benzamidas sustituidas y métodos para utilizarlas |
| EP3341353A1 (en) | 2015-08-27 | 2018-07-04 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| PE20181003A1 (es) | 2015-09-28 | 2018-06-26 | Genentech Inc | Compuestos terapeuticos y sus metodos de uso |
| WO2017091592A1 (en) | 2015-11-25 | 2017-06-01 | Genentech, Inc. | Substituted benzamides useful as sodium channel blockers |
| EP3436432B1 (en) | 2016-03-30 | 2021-01-27 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
| PL3436446T3 (pl) | 2016-03-31 | 2023-09-11 | Vertex Pharmaceuticals Incorporated | Modulatory mukowiscydozowego przezbłonowego regulatora przewodnictwa |
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- 2005-09-26 MX MX2007003836A patent/MX2007003836A/es active IP Right Grant
- 2005-09-26 CN CN2005800328848A patent/CN101031565B/zh not_active Expired - Fee Related
- 2005-09-26 NZ NZ554211A patent/NZ554211A/en not_active IP Right Cessation
- 2005-09-26 KR KR1020077009902A patent/KR20070064356A/ko not_active Ceased
- 2005-09-26 US US11/236,051 patent/US7205296B2/en not_active Expired - Lifetime
- 2005-09-26 JP JP2007534673A patent/JP2008514703A/ja not_active Ceased
- 2005-09-26 WO PCT/US2005/034246 patent/WO2006039212A2/en not_active Ceased
- 2005-09-26 ZA ZA200702688A patent/ZA200702688B/en unknown
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| NZ554211A (en) | 2010-10-29 |
| MX2007003836A (es) | 2007-08-20 |
| BRPI0516181A (pt) | 2008-08-26 |
| ZA200702688B (en) | 2008-06-25 |
| WO2006039212A3 (en) | 2007-01-25 |
| AU2005292314A1 (en) | 2006-04-13 |
| US7205296B2 (en) | 2007-04-17 |
| CN101031565B (zh) | 2010-09-29 |
| US20060069093A1 (en) | 2006-03-30 |
| CN101031565A (zh) | 2007-09-05 |
| AU2005292314B2 (en) | 2011-11-03 |
| WO2006039212A2 (en) | 2006-04-13 |
| IL182180A0 (en) | 2007-07-24 |
| HK1111414A1 (en) | 2008-08-08 |
| CA2581638A1 (en) | 2006-04-13 |
| EP1812429A2 (en) | 2007-08-01 |
| KR20070064356A (ko) | 2007-06-20 |
| EP1812429A4 (en) | 2010-07-21 |
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