JP2007507551A - ２，４−ジオキソ−３−キナゾリニルアリールスルホニル尿素 - Google Patents
２，４−ジオキソ−３−キナゾリニルアリールスルホニル尿素 Download PDFInfo
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- JP2007507551A JP2007507551A JP2006534290A JP2006534290A JP2007507551A JP 2007507551 A JP2007507551 A JP 2007507551A JP 2006534290 A JP2006534290 A JP 2006534290A JP 2006534290 A JP2006534290 A JP 2006534290A JP 2007507551 A JP2007507551 A JP 2007507551A
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- Prior art keywords
- alkyl
- group
- alkoxy
- cycloalkyl
- compound
- Prior art date
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- -1 2,4-Dioxo-3-quinazolinyl Chemical group 0.000 claims abstract description 81
- 238000011282 treatment Methods 0.000 claims abstract description 25
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims description 183
- 125000000217 alkyl group Chemical group 0.000 claims description 161
- 125000003545 alkoxy group Chemical group 0.000 claims description 84
- 238000000034 method Methods 0.000 claims description 74
- 229910052736 halogen Inorganic materials 0.000 claims description 68
- 150000002367 halogens Chemical class 0.000 claims description 68
- 229910052799 carbon Inorganic materials 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 125000001424 substituent group Chemical group 0.000 claims description 40
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 32
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 29
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 28
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 28
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 24
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 24
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 20
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 18
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 18
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 18
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 18
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 18
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 16
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 15
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 14
- 239000003146 anticoagulant agent Substances 0.000 claims description 14
- 125000005647 linker group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 11
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 9
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 9
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 9
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 9
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 9
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 9
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 9
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 9
- 229930192474 thiophene Natural products 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 7
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 230000000302 ischemic effect Effects 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 229940124597 therapeutic agent Drugs 0.000 claims description 6
- 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 claims description 5
- 239000005557 antagonist Substances 0.000 claims description 5
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 5
- 230000000702 anti-platelet effect Effects 0.000 claims description 5
- 229940127219 anticoagulant drug Drugs 0.000 claims description 5
- 125000002393 azetidinyl group Chemical group 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 206010002388 Angina unstable Diseases 0.000 claims description 4
- 208000007718 Stable Angina Diseases 0.000 claims description 4
- 208000007814 Unstable Angina Diseases 0.000 claims description 4
- 239000003527 fibrinolytic agent Substances 0.000 claims description 4
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 4
- 230000001732 thrombotic effect Effects 0.000 claims description 4
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 claims description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 229960002897 heparin Drugs 0.000 claims description 3
- 229920000669 heparin Polymers 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 201000010875 transient cerebral ischemia Diseases 0.000 claims description 3
- 206010022562 Intermittent claudication Diseases 0.000 claims description 2
- 206010038563 Reocclusion Diseases 0.000 claims description 2
- 206010050496 Reversible ischaemic neurological deficit Diseases 0.000 claims description 2
- 229940122388 Thrombin inhibitor Drugs 0.000 claims description 2
- 208000032109 Transient ischaemic attack Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 239000003529 anticholesteremic agent Substances 0.000 claims description 2
- 229940127226 anticholesterol agent Drugs 0.000 claims description 2
- 239000002220 antihypertensive agent Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000007887 coronary angioplasty Methods 0.000 claims description 2
- 229940072645 coumadin Drugs 0.000 claims description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 2
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 2
- 229940118179 lovenox Drugs 0.000 claims description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 2
- 239000002570 phosphodiesterase III inhibitor Substances 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 239000003868 thrombin inhibitor Substances 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims 7
- 125000004438 haloalkoxy group Chemical group 0.000 claims 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 claims 1
- 229940123987 Thromboxane A2 receptor antagonist Drugs 0.000 claims 1
- 239000003420 antiserotonin agent Substances 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 239000003769 thromboxane A2 receptor blocking agent Substances 0.000 claims 1
- 108010085249 Purinergic P2 Receptors Proteins 0.000 abstract description 14
- 208000010110 spontaneous platelet aggregation Diseases 0.000 abstract description 9
- 230000002785 anti-thrombosis Effects 0.000 abstract description 6
- 239000003112 inhibitor Substances 0.000 abstract description 5
- 230000002265 prevention Effects 0.000 abstract description 5
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 102000007466 Purinergic P2 Receptors Human genes 0.000 abstract 2
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
- 239000000047 product Substances 0.000 description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- 0 *C1CCC(CCC*(C*2)=CC3C2[C@@](*)*(C(CC2**=C4)C=CC2C4O)C(*)*CC3)CC1 Chemical compound *C1CCC(CCC*(C*2)=CC3C2[C@@](*)*(C(CC2**=C4)C=CC2C4O)C(*)*CC3)CC1 0.000 description 21
- 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
- 239000007787 solid Substances 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 102100037600 P2Y purinoceptor 1 Human genes 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 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
- 239000000872 buffer Substances 0.000 description 8
- 239000004202 carbamide Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000002776 aggregation Effects 0.000 description 7
- 238000004220 aggregation Methods 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical group C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- 239000012948 isocyanate Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 102000007347 Apyrase Human genes 0.000 description 5
- 108010007730 Apyrase Proteins 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
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- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 5
- 125000003107 substituted aryl group Chemical group 0.000 description 5
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical group OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 5
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 4
- NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-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
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
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- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
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- 238000004128 high performance liquid chromatography Methods 0.000 description 4
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- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- STJREYBUZMZWAI-UHFFFAOYSA-N methyl 4-[(2-methylpropan-2-yl)oxycarbonylamino]-2-nitrobenzoate Chemical compound COC(=O)C1=CC=C(NC(=O)OC(C)(C)C)C=C1[N+]([O-])=O STJREYBUZMZWAI-UHFFFAOYSA-N 0.000 description 4
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- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical class CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 3
- XIWRCSVXKPGGAJ-UHFFFAOYSA-N 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-(4-chlorophenyl)urea Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC1=CC=C(Cl)C=C1 XIWRCSVXKPGGAJ-UHFFFAOYSA-N 0.000 description 3
- GFNKTLQTQSALEJ-UHFFFAOYSA-N 1-isocyanato-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(N=C=O)C=C1 GFNKTLQTQSALEJ-UHFFFAOYSA-N 0.000 description 3
- KTFDYVNEGTXQCV-UHFFFAOYSA-N 2-Thiophenesulfonamide Chemical class NS(=O)(=O)C1=CC=CS1 KTFDYVNEGTXQCV-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
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- Hydrogenated Pyridines (AREA)
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- Non-Alcoholic Beverages (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US50856403P | 2003-10-03 | 2003-10-03 | |
| PCT/US2004/032921 WO2005032488A2 (en) | 2003-10-03 | 2004-09-29 | 2,4-dioxo-3-quinazolinylaryl sulfonylureas |
Publications (2)
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| JP2007507551A true JP2007507551A (ja) | 2007-03-29 |
| JP2007507551A5 JP2007507551A5 (enExample) | 2007-11-08 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008514703A (ja) * | 2004-09-29 | 2008-05-08 | ポートラ ファーマシューティカルズ， インコーポレイテッド | 置換２ｈ−１，３−ベンゾオキサジン−４（３ｈ）−オン |
| JP2012515224A (ja) * | 2009-01-19 | 2012-07-05 | アボット・ラボラトリーズ | 癌並びに免疫及び自己免疫疾患の治療用アポトーシス誘導剤 |
| 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 |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2390520C2 (ru) * | 2003-12-22 | 2010-05-27 | Адзиномото Ко., Инк. | Новые производные фенилаланина |
| AU2006311795B2 (en) * | 2005-11-03 | 2013-01-17 | Portola Pharmaceuticals, Inc. | [4-(6-halo-7-substituted-2,4-dioxo-1,4-dihydro-2h-quinazolin-3-yl)-phenyl]-5-chloro-thiophen-2-yl-sulfonylureas and forms and methods related thereto |
| US7834023B2 (en) * | 2006-09-20 | 2010-11-16 | Portola Pharmaceuticals, Inc. | Substituted dihydroquinazolines as platelet ADP receptor inhibitors |
| CA2682207A1 (en) | 2007-04-05 | 2008-10-16 | Cv Therapeutics, Inc. | Quinazolinone derivatives as aldh-2 inhibitors |
| WO2008133155A1 (ja) | 2007-04-19 | 2008-11-06 | Astellas Pharma Inc. | 二環式ヘテロ環化合物 |
| KR20100020455A (ko) * | 2007-05-02 | 2010-02-22 | 포톨라 파마슈티컬스, 인코포레이티드 | 상이한 결정질 형태의 [4-(6-플루오로-7-메틸아미노-2,4-디옥소-1,4-디히드로-2ｈ-퀴나졸린-3-일)-페닐]-5-클로로-티오펜-2-일-술포닐우레아염, 및 이의 제약 조성물 |
| CN101654441B (zh) * | 2008-08-19 | 2012-10-03 | 信谊药厂 | 抗凝化合物、组合物及其用途 |
| CN102282129A (zh) | 2009-01-19 | 2011-12-14 | 雅培制药有限公司 | 用于治疗癌症和免疫和自身免疫疾病的细胞程序死亡诱导药剂 |
| KR20140091022A (ko) | 2011-10-31 | 2014-07-18 | 제논 파마슈티칼스 인크. | 벤젠술폰아미드 화합물 및 치료제로서의 그의 용도 |
| JP6014155B2 (ja) | 2011-10-31 | 2016-10-25 | ゼノン・ファーマシューティカルズ・インコーポレイテッドＸｅｎｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃ． | ビアリールエーテルスルホンアミドおよび治療剤としてのそれらの使用 |
| WO2014008458A2 (en) | 2012-07-06 | 2014-01-09 | Genentech, Inc. | N-substituted benzamides and methods of use thereof |
| MX2015011436A (es) | 2013-03-14 | 2016-06-06 | Genentech Inc | Triazolopiridinas sustituidas y metodos para usarlas. |
| MX2015010775A (es) | 2013-03-15 | 2016-04-25 | Genentech Inc | Benzoxazoles sustituidos y metodos para usarlos. |
| CN105793238B (zh) | 2013-11-27 | 2019-12-24 | 基因泰克公司 | 经取代的苯甲酰胺及其使用方法 |
| EP3166939B1 (en) | 2014-07-07 | 2019-06-05 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| CN113582889B (zh) | 2015-02-16 | 2024-09-20 | 昆士兰大学 | 磺酰脲和相关化合物及其用途 |
| US10179767B2 (en) | 2015-05-22 | 2019-01-15 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
| MA42683A (fr) | 2015-08-27 | 2018-07-04 | Genentech Inc | Composés thérapeutiques et leurs méthodes utilisation |
| SG10202007787RA (en) | 2015-09-28 | 2020-09-29 | Genentech Inc | Therapeutic compounds and methods of use thereof |
| JP2018535234A (ja) | 2015-11-25 | 2018-11-29 | ジェネンテック， インコーポレイテッド | ナトリウムチャネル遮断薬として有用な置換ベンズアミド |
| EP3854782A1 (en) | 2016-03-30 | 2021-07-28 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
| KR20190078587A (ko) | 2016-10-17 | 2019-07-04 | 제넨테크, 인크. | 치료 화합물 및 그의 사용 방법 |
| CN110546148A (zh) | 2017-03-24 | 2019-12-06 | 基因泰克公司 | 作为钠通道抑制剂的4-哌啶-n-(嘧啶-4-基)色满-7-磺酰胺衍生物 |
| WO2019008025A1 (en) | 2017-07-07 | 2019-01-10 | Inflazome Limited | NOVEL CARBOXAMIDE SULFONAMIDE COMPOUNDS |
| WO2019034693A1 (en) | 2017-08-15 | 2019-02-21 | Inflazome Limited | SULFONYLURATES AND SULFONYLTHIOURES AS INHIBITORS OF NLRP3 |
| WO2019034692A1 (en) | 2017-08-15 | 2019-02-21 | Inflazome Limited | SULFONYLURATES AND SULFONYLTHIOURES AS INHIBITORS OF NLRP3 |
| BR112020003014A2 (pt) | 2017-08-15 | 2020-07-28 | Inflazome Limited | sulfonilureias e sulfoniltioureias como inibidores de vnlrp3 |
| US12221434B2 (en) | 2017-11-09 | 2025-02-11 | Inflazome Limited | Sulfonamide carboxamide compounds |
| CA3078195A1 (en) | 2017-11-09 | 2019-05-16 | Inflazome Limited | Novel sulfonamide carboxamide compounds |
| US11028075B2 (en) | 2018-02-26 | 2021-06-08 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| WO2019166619A1 (en) | 2018-03-02 | 2019-09-06 | Inflazome Limited | Novel compounds |
| US10947251B2 (en) | 2018-03-30 | 2021-03-16 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| TW202003490A (zh) | 2018-05-22 | 2020-01-16 | 瑞士商赫孚孟拉羅股份公司 | 治療性化合物及其使用方法 |
| CN113164481B (zh) | 2018-12-06 | 2024-08-30 | 第一三共株式会社 | 环烷-1,3-二胺衍生物 |
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| JP2003522177A (ja) * | 2000-02-04 | 2003-07-22 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | 血小板ａｄｐレセプターインヒビター |
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| SE9702774D0 (sv) | 1997-07-22 | 1997-07-22 | Astra Pharma Prod | Novel compounds |
| EP1047699A1 (en) | 1998-01-15 | 2000-11-02 | Cor Therapeutics, Inc. | Platelet adp receptor inhibitors |
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2004
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- 2004-09-29 EP EP04789522A patent/EP1668002B1/en not_active Expired - Lifetime
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003522177A (ja) * | 2000-02-04 | 2003-07-22 | ミレニアム・ファーマシューティカルズ・インコーポレイテッド | 血小板ａｄｐレセプターインヒビター |
| WO2003011872A1 (en) * | 2001-08-02 | 2003-02-13 | Millennium Pharmaceuticals, Inc. | Platelet adp receptor inhibitors |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008514703A (ja) * | 2004-09-29 | 2008-05-08 | ポートラ ファーマシューティカルズ， インコーポレイテッド | 置換２ｈ−１，３−ベンゾオキサジン−４（３ｈ）−オン |
| JP2012515224A (ja) * | 2009-01-19 | 2012-07-05 | アボット・ラボラトリーズ | 癌並びに免疫及び自己免疫疾患の治療用アポトーシス誘導剤 |
| 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 |
Also Published As
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| CN1863798A (zh) | 2006-11-15 |
| PT1668002E (pt) | 2009-11-25 |
| WO2005032488A3 (en) | 2005-05-12 |
| HK1093973A1 (en) | 2007-03-16 |
| WO2005032488A2 (en) | 2005-04-14 |
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| US20050107357A1 (en) | 2005-05-19 |
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| MXPA06003618A (es) | 2006-08-11 |
| EP1668002B1 (en) | 2009-11-11 |
| PL1668002T3 (pl) | 2010-02-26 |
| AU2004278030B2 (en) | 2010-07-01 |
| DE602004024093D1 (de) | 2009-12-24 |
| US7109332B2 (en) | 2006-09-19 |
| AU2004278030C1 (en) | 2010-12-02 |
| KR20060113700A (ko) | 2006-11-02 |
| EP1668002A2 (en) | 2006-06-14 |
| CN1863798B (zh) | 2011-08-31 |
| IL174446A (en) | 2012-02-29 |
| IL174446A0 (en) | 2006-08-01 |
| AU2004278030A1 (en) | 2005-04-14 |
| ATE448222T1 (de) | 2009-11-15 |
| ES2334795T3 (es) | 2010-03-16 |
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