KR20070064356A - 치환된 2ｈ-1,3-벤족사진-4(3ｈ)온 - Google Patents
치환된 2ｈ-1,3-벤족사진-4(3ｈ)온 Download PDFInfo
- Publication number
- KR20070064356A KR20070064356A KR1020077009902A KR20077009902A KR20070064356A KR 20070064356 A KR20070064356 A KR 20070064356A KR 1020077009902 A KR1020077009902 A KR 1020077009902A KR 20077009902 A KR20077009902 A KR 20077009902A KR 20070064356 A KR20070064356 A KR 20070064356A
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- KR
- South Korea
- Prior art keywords
- alkyl
- group
- cycloalkyl
- compound
- alkoxy
- 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.)
- Ceased
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- 208000007536 Thrombosis Diseases 0.000 claims abstract description 16
- 208000028867 ischemia Diseases 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 132
- 125000000217 alkyl group Chemical group 0.000 claims description 103
- 238000000034 method Methods 0.000 claims description 86
- -1 cyano, hydroxy Chemical group 0.000 claims description 68
- 229910052799 carbon Inorganic materials 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 150000002367 halogens Chemical class 0.000 claims description 36
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 239000008194 pharmaceutical composition Substances 0.000 claims description 25
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 19
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 15
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- 239000003146 anticoagulant agent Substances 0.000 claims description 11
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 10
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 9
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 9
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 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 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
- 239000005557 antagonist Substances 0.000 claims description 6
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 5
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 125000005647 linker group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 206010002388 Angina unstable Diseases 0.000 claims description 4
- 208000007718 Stable Angina Diseases 0.000 claims description 4
- 208000032109 Transient ischaemic attack Diseases 0.000 claims description 4
- 208000007814 Unstable Angina Diseases 0.000 claims description 4
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 4
- 230000000702 anti-platelet effect Effects 0.000 claims description 4
- 229940127219 anticoagulant drug Drugs 0.000 claims description 4
- 238000011161 development Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 201000010875 transient cerebral ischemia Diseases 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
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 3
- 229960002897 heparin Drugs 0.000 claims description 3
- 229920000669 heparin Polymers 0.000 claims description 3
- 230000000302 ischemic effect Effects 0.000 claims description 3
- 229940118179 lovenox Drugs 0.000 claims description 3
- 229940122388 Thrombin inhibitor Drugs 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
- 230000036772 blood pressure Effects 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 238000007887 coronary angioplasty Methods 0.000 claims description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 210000005036 nerve Anatomy 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
- 230000002441 reversible effect Effects 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 229940076279 serotonin Drugs 0.000 claims description 2
- 239000003868 thrombin inhibitor Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 229940124597 therapeutic agent Drugs 0.000 claims 4
- 229940123987 Thromboxane A2 receptor antagonist Drugs 0.000 claims 1
- 230000007812 deficiency Effects 0.000 claims 1
- 230000003480 fibrinolytic effect Effects 0.000 claims 1
- 208000030175 lameness Diseases 0.000 claims 1
- 239000003769 thromboxane A2 receptor blocking agent Substances 0.000 claims 1
- 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
- 210000001772 blood platelet Anatomy 0.000 description 38
- 230000008569 process Effects 0.000 description 31
- 239000000243 solution Substances 0.000 description 27
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 26
- 239000000203 mixture Substances 0.000 description 22
- 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
- 238000006243 chemical reaction Methods 0.000 description 18
- QHIIPTWSKPGKPZ-UHFFFAOYSA-N (2-carbonochloridoyl-4,5-difluorophenyl) acetate Chemical compound CC(=O)OC1=CC(F)=C(F)C=C1C(Cl)=O QHIIPTWSKPGKPZ-UHFFFAOYSA-N 0.000 description 17
- 230000027455 binding Effects 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 16
- YUEDYKGJCNMJDQ-UHFFFAOYSA-N sulfonylurea;urea Chemical compound NC(N)=O.NC(=O)N=S(=O)=O YUEDYKGJCNMJDQ-UHFFFAOYSA-N 0.000 description 15
- 0 CI1(*)=CSC(S(NC(NC(N=C2)=C*(*)C=C2N(C(*)(*)Oc(c2c3)c(*)c(N(*)*)c3F)C2=O)=O)#C)=CC1 Chemical compound CI1(*)=CSC(S(NC(NC(N=C2)=C*(*)C=C2N(C(*)(*)Oc(c2c3)c(*)c(N(*)*)c3F)C2=O)=O)#C)=CC1 0.000 description 14
- 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
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 14
- 229920002866 paraformaldehyde Polymers 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 102100037600 P2Y purinoceptor 1 Human genes 0.000 description 12
- 108010085249 Purinergic P2 Receptors Proteins 0.000 description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- 229910052731 fluorine Inorganic materials 0.000 description 10
- 239000011737 fluorine Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229940100389 Sulfonylurea Drugs 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000005755 formation reaction Methods 0.000 description 9
- 238000004007 reversed phase HPLC Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 9
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-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
- 230000001351 cycling effect Effects 0.000 description 8
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 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 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 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 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
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 230000002776 aggregation Effects 0.000 description 6
- 238000004220 aggregation Methods 0.000 description 6
- 150000001412 amines Chemical class 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
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- TZBHPYXJOJGKDT-UHFFFAOYSA-N 1,3-oxazin-4-one Chemical compound O=C1C=COC=N1 TZBHPYXJOJGKDT-UHFFFAOYSA-N 0.000 description 5
- 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 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
- 230000002785 anti-thrombosis Effects 0.000 description 5
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- 102000005962 receptors Human genes 0.000 description 5
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- 125000001424 substituent group Chemical group 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
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- 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 238000002399 angioplasty Methods 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
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- 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
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- OQKYGBNJIBWJQS-UHFFFAOYSA-N 1,3-benzoxazin-4-one Chemical compound C1=CC=C2C(=O)N=COC2=C1 OQKYGBNJIBWJQS-UHFFFAOYSA-N 0.000 description 3
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- 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
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- 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
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Classifications
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- 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
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- 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
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- 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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- 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)
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- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
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| US8952169B2 (en) | 2012-05-22 | 2015-02-10 | Xenon Pharmaceuticals Inc. | N-substituted benzamides and methods of use thereof |
| CN104797555B (zh) | 2012-07-06 | 2017-12-22 | 基因泰克公司 | N‑取代的苯甲酰胺及其使用方法 |
| US9469654B2 (en) | 2012-09-27 | 2016-10-18 | Portola Pharmaceuticals, Inc. | Bicyclic oxa-lactam kinase inhibitors |
| HK1213476A1 (zh) | 2013-03-14 | 2016-07-08 | 基因泰克公司 | 取代的三唑並吡啶及其使用方法 |
| CA2898680A1 (en) | 2013-03-15 | 2014-09-18 | Genentech,Inc. | Substituted benzoxazoles and methods of use thereof |
| CA2931732A1 (en) | 2013-11-27 | 2015-06-04 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
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| IL313498A (en) | 2014-10-06 | 2024-08-01 | Vertex Pharma | Modulators of the cystic fibrosis transmembrane conductance regulator |
| AU2016222278B2 (en) | 2015-02-16 | 2020-07-09 | The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | Sulfonylureas and related compounds and use of same |
| PE20180575A1 (es) | 2015-05-22 | 2018-04-04 | Genentech Inc | Benzamidas sustituidas y metodos para utilizarlas |
| MA42683A (fr) | 2015-08-27 | 2018-07-04 | Genentech Inc | Composés thérapeutiques et leurs méthodes utilisation |
| BR112018006189A2 (pt) | 2015-09-28 | 2018-10-09 | Genentech Inc | compostos da fórmula, composição farmacêutica, métodos de tratamento de uma doença, de diminuição do fluxo de íons e de tratamento de prurido em um mamífero, método para tratamento de dores em um mamífero e uso de um composto |
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| HRP20211683T1 (hr) | 2016-09-30 | 2022-03-04 | Vertex Pharmaceuticals Incorporated | Modulator transmembranskog regulatora provodljivosti cistične fibroze, farmaceutski pripravci, postupci liječenja, i postupak za pripravu modulatora |
| WO2018072602A1 (en) | 2016-10-17 | 2018-04-26 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| MX2021013639A (es) | 2016-12-09 | 2022-09-30 | Vertex Pharma | Forma cristalina del compuesto 1, un modulador del regulador de conductancia transmembrana de fibrosis quística, procesos para su preparación, composiciones farmacéuticas del compuesto 1, y su uso en el tratamiento de fibrosis quística. |
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| AU2018279646B2 (en) | 2017-06-08 | 2023-04-06 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| LT3661925T (lt) | 2017-07-07 | 2022-03-10 | Inflazome Limited | Naujieji sulfonamido karboksamido junginiai |
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| TW201910317A (zh) | 2017-08-15 | 2019-03-16 | 愛爾蘭商英弗雷佐姆有限公司 | 新穎化合物 |
| US11926600B2 (en) | 2017-08-15 | 2024-03-12 | Inflazome Limited | Sulfonylureas and sulfonylthioureas as NLRP3 inhibitors |
| CA3071150A1 (en) | 2017-08-15 | 2019-02-21 | Inflazome Limited | Sulfonylureas and sulfonylthioureas as nlrp3 inhibitors |
| WO2019074979A1 (en) | 2017-10-09 | 2019-04-18 | Girafpharma, Llc | HETEROCYCLIC COMPOUNDS AND USES THEREOF |
| US10807994B2 (en) | 2017-10-09 | 2020-10-20 | Nuvation Bio Inc. | Heterocyclic compounds and uses thereof |
| WO2019079760A1 (en) | 2017-10-19 | 2019-04-25 | Vertex Pharmaceuticals Incorporated | CRYSTALLINE FORMS AND COMPOSITIONS OF CFTR MODULATORS |
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| RU2020115098A (ru) | 2017-11-09 | 2021-12-10 | Инфлазоум Лимитед | Соединения новых сульфонамидкарбоксамидов |
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| EP3759098A1 (en) | 2018-02-26 | 2021-01-06 | Genentech, Inc. | Pyridine-sulfonamide compounds and their use against pain and related conditions |
| EP3759077A1 (en) | 2018-03-02 | 2021-01-06 | Inflazome Limited | Novel compounds |
| US10947251B2 (en) | 2018-03-30 | 2021-03-16 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
| WO2019200246A1 (en) | 2018-04-13 | 2019-10-17 | Alexander Russell Abela | Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator |
| 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 |
| US20220168313A1 (en) * | 2019-04-09 | 2022-06-02 | Nuvation Bio Inc. | Heterocyclic compounds and uses thereof |
| KR20210150476A (ko) | 2019-04-09 | 2021-12-10 | 누베이션 바이오 인크. | 헤테로시클릭 화합물 및 그의 용도 |
| WO2020210377A1 (en) * | 2019-04-09 | 2020-10-15 | Nuvation Bio Inc. | Heterocyclic compounds and uses thereof |
| NZ789439A (en) * | 2019-12-10 | 2025-07-25 | Shanghai Zhimeng Biopharma Inc | Compound having neuroprotective effect, preparation method therefor and use thereof |
| US11685727B2 (en) | 2019-12-20 | 2023-06-27 | Nuevolution A/S | Compounds active towards nuclear receptors |
| JP2021098692A (ja) | 2019-12-20 | 2021-07-01 | ヌエヴォリューション・アクティーゼルスカブＮｕｅｖｏｌｕｔｉｏｎ Ａ／Ｓ | 核内受容体に対して活性の化合物 |
| JP7713954B2 (ja) | 2020-03-31 | 2025-07-28 | ヌエヴォリューション・アクティーゼルスカブ | 核内受容体に対して活性な化合物 |
| MX2022012260A (es) | 2020-03-31 | 2022-11-30 | Nuevolution As | Compuestos activos frente a receptores nucleares. |
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| FI101150B (fi) | 1991-09-09 | 1998-04-30 | Sankyo Co | Menetelmä lääkeaineina käyttökelpoisten tetrahydrotienopyridiinin johd annaisten valmistamiseksi |
| FR2702477B1 (fr) * | 1993-03-08 | 1995-04-28 | Synthelabo | Dérivés de benzoxazine, leur préparation et leur application en thérapeutique. |
| JP3814742B2 (ja) * | 1996-10-18 | 2006-08-30 | イハラケミカル工業株式会社 | ４−フルオロサリチル酸類 |
| SE9702774D0 (sv) | 1997-07-22 | 1997-07-22 | Astra Pharma Prod | Novel compounds |
| JP2002509152A (ja) | 1998-01-15 | 2002-03-26 | シーオーアール セラピューティクス インコーポレイテッド | 血小板ａｄｐ受容体阻害剤 |
| JP4588877B2 (ja) | 1998-06-17 | 2010-12-01 | ブリストル−マイヤーズ スクイブ カンパニー | Ａｄｐ−受容体抗血小板物質と抗高血圧薬の組合せ投与による脳梗塞の予防 |
| US6509348B1 (en) | 1998-11-03 | 2003-01-21 | Bristol-Myers Squibb Company | Combination of an ADP-receptor blocking antiplatelet drug and a thromboxane A2 receptor antagonist and a method for inhibiting thrombus formation employing such combination |
| DE60114994T2 (de) * | 2000-02-04 | 2006-08-03 | Portola Pharmaceuticals, Inc., South San Francisco | Blutplättchen-adp-rezeptor-inhibitoren |
| US6906063B2 (en) * | 2000-02-04 | 2005-06-14 | Portola Pharmaceuticals, Inc. | Platelet ADP receptor inhibitors |
| US7405051B2 (en) | 2000-11-01 | 2008-07-29 | Astellas Pharma Inc. | Method of screening antiplatelet agents |
| US6861424B2 (en) | 2001-06-06 | 2005-03-01 | Schering Aktiengesellschaft | Platelet adenosine diphosphate receptor antagonists |
| JPWO2004052871A1 (ja) * | 2002-12-06 | 2006-04-13 | 東レ株式会社 | ベンゾモルホリン誘導体 |
| JP4879745B2 (ja) * | 2003-10-03 | 2012-02-22 | 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 | 置換イソキノリノン |
| PL1668002T3 (pl) * | 2003-10-03 | 2010-02-26 | Portola Pharm Inc | 2,4-diokso-3-chinazolinyloarylowe pochodne sulfonylomocznika |
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- 2005-09-26 KR KR1020077009902A patent/KR20070064356A/ko not_active Ceased
- 2005-09-26 NZ NZ554211A patent/NZ554211A/en not_active IP Right Cessation
- 2005-09-26 WO PCT/US2005/034246 patent/WO2006039212A2/en not_active Ceased
- 2005-09-26 BR BRPI0516181-9A patent/BRPI0516181A/pt not_active IP Right Cessation
- 2005-09-26 CA CA002581638A patent/CA2581638A1/en not_active Abandoned
- 2005-09-26 EP EP05798632A patent/EP1812429A4/en not_active Withdrawn
- 2005-09-26 CN CN2005800328848A patent/CN101031565B/zh not_active Expired - Fee Related
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- 2005-09-26 JP JP2007534673A patent/JP2008514703A/ja not_active Ceased
- 2005-09-26 US US11/236,051 patent/US7205296B2/en not_active Expired - Lifetime
- 2005-09-26 ZA ZA200702688A patent/ZA200702688B/en unknown
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2007
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Also Published As
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| BRPI0516181A (pt) | 2008-08-26 |
| EP1812429A4 (en) | 2010-07-21 |
| WO2006039212A3 (en) | 2007-01-25 |
| US7205296B2 (en) | 2007-04-17 |
| AU2005292314A1 (en) | 2006-04-13 |
| ZA200702688B (en) | 2008-06-25 |
| CN101031565B (zh) | 2010-09-29 |
| CA2581638A1 (en) | 2006-04-13 |
| NZ554211A (en) | 2010-10-29 |
| AU2005292314B2 (en) | 2011-11-03 |
| EP1812429A2 (en) | 2007-08-01 |
| IL182180A0 (en) | 2007-07-24 |
| MX2007003836A (es) | 2007-08-20 |
| WO2006039212A2 (en) | 2006-04-13 |
| US20060069093A1 (en) | 2006-03-30 |
| HK1111414A1 (en) | 2008-08-08 |
| CN101031565A (zh) | 2007-09-05 |
| JP2008514703A (ja) | 2008-05-08 |
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