JP2008527042A - 進行性多病巣性白質脳障害の予防または治療に有用な、5−ht2aセロトニン受容体の調節因子としてのジアリールおよびアリールヘテロアリール尿素誘導体 - Google Patents
進行性多病巣性白質脳障害の予防または治療に有用な、5−ht2aセロトニン受容体の調節因子としてのジアリールおよびアリールヘテロアリール尿素誘導体 Download PDFInfo
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- JP2008527042A JP2008527042A JP2007552201A JP2007552201A JP2008527042A JP 2008527042 A JP2008527042 A JP 2008527042A JP 2007552201 A JP2007552201 A JP 2007552201A JP 2007552201 A JP2007552201 A JP 2007552201A JP 2008527042 A JP2008527042 A JP 2008527042A
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- phenyl
- methyl
- pyrazol
- urea
- chloro
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- 238000011282 treatment Methods 0.000 title claims abstract description 90
- 230000002265 prevention Effects 0.000 title claims abstract description 78
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 title claims abstract description 76
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 title abstract description 68
- 150000003672 ureas Chemical class 0.000 title abstract description 29
- 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 title abstract description 3
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 718
- 238000000034 method Methods 0.000 claims abstract description 164
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 68
- -1 C 1 to 6 alkylureyl Chemical group 0.000 claims description 221
- 125000000217 alkyl group Chemical group 0.000 claims description 155
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 118
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 115
- 229910052736 halogen Inorganic materials 0.000 claims description 112
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 110
- 150000002367 halogens Chemical class 0.000 claims description 108
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 96
- 125000003545 alkoxy group Chemical group 0.000 claims description 94
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 86
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 84
- 125000001424 substituent group Chemical group 0.000 claims description 70
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 66
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 65
- 125000002252 acyl group Chemical group 0.000 claims description 64
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 62
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 60
- 125000005392 carboxamide group Chemical class NC(=O)* 0.000 claims description 60
- 229910052799 carbon Inorganic materials 0.000 claims description 58
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 57
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 55
- 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 51
- 125000000623 heterocyclic group Chemical group 0.000 claims description 49
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 48
- 125000005432 dialkylcarboxamide group Chemical group 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 44
- 125000004423 acyloxy group Chemical group 0.000 claims description 43
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 39
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 37
- 125000001072 heteroaryl group Chemical group 0.000 claims description 37
- 238000002360 preparation method Methods 0.000 claims description 37
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 35
- 125000001246 bromo group Chemical group Br* 0.000 claims description 35
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 35
- 125000003282 alkyl amino group Chemical group 0.000 claims description 34
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 34
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 33
- 125000004414 alkyl thio group Chemical group 0.000 claims description 32
- 239000003937 drug carrier Substances 0.000 claims description 31
- 125000005277 alkyl imino group Chemical group 0.000 claims description 27
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 27
- 125000000304 alkynyl group Chemical group 0.000 claims description 27
- 125000001188 haloalkyl group Chemical group 0.000 claims description 27
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 26
- 229940125425 inverse agonist Drugs 0.000 claims description 24
- 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 24
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 22
- 125000004749 (C1-C6) haloalkylsulfinyl group Chemical group 0.000 claims description 22
- 229940124530 sulfonamide Drugs 0.000 claims description 22
- 125000005363 dialkylsulfonamide group Chemical group 0.000 claims description 21
- 150000003456 sulfonamides Chemical class 0.000 claims description 21
- 125000004429 atom Chemical group 0.000 claims description 20
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 19
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 19
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 claims description 18
- 125000004440 haloalkylsulfinyl group Chemical group 0.000 claims description 18
- 125000001624 naphthyl group Chemical group 0.000 claims description 18
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 206010001513 AIDS related complex Diseases 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 238000002650 immunosuppressive therapy Methods 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
- 239000012453 solvate Substances 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 206010061598 Immunodeficiency Diseases 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 208000030507 AIDS Diseases 0.000 claims description 8
- 208000030289 Lymphoproliferative disease Diseases 0.000 claims description 8
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 7
- 201000001268 lymphoproliferative syndrome Diseases 0.000 claims description 7
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 6
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 239000004202 carbamide Substances 0.000 claims 6
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 5
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 2
- BQJBONTVMVGWPV-UHFFFAOYSA-N (2-hydroxyphenyl)urea Chemical compound NC(=O)NC1=CC=CC=C1O BQJBONTVMVGWPV-UHFFFAOYSA-N 0.000 claims 1
- LSSTXJCXCLJISH-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[3-(2-methylpyrazol-3-yl)-4-(trifluoromethoxy)phenyl]urea Chemical compound CN1N=CC=C1C1=CC(NC(=O)NC=2C(=CC(F)=CC=2)F)=CC=C1OC(F)(F)F LSSTXJCXCLJISH-UHFFFAOYSA-N 0.000 claims 1
- KSEJHUHTJQBSMA-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[4-[2-(dimethylamino)ethoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(F)C=C1F KSEJHUHTJQBSMA-UHFFFAOYSA-N 0.000 claims 1
- USCDCYATSWIFJG-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[4-[2-(dimethylamino)ethoxy]-3-(4-fluoro-2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2F)C)C(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(F)C=C1F USCDCYATSWIFJG-UHFFFAOYSA-N 0.000 claims 1
- CSHXEKZUWVQYQJ-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[4-[3-(dimethylamino)propoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=C(F)C=C1F CSHXEKZUWVQYQJ-UHFFFAOYSA-N 0.000 claims 1
- XTTKHALPTNRMOX-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[4-[3-(dimethylamino)propoxy]-3-(4-fluoro-2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2F)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=C(F)C=C1F XTTKHALPTNRMOX-UHFFFAOYSA-N 0.000 claims 1
- WDCATRUABRXGNV-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[4-methoxy-3-(1h-pyrazol-5-yl)phenyl]urea Chemical compound C1=C(C=2NN=CC=2)C(OC)=CC=C1NC(=O)NC1=CC=C(F)C=C1F WDCATRUABRXGNV-UHFFFAOYSA-N 0.000 claims 1
- AKRRFFJBSRFAKM-UHFFFAOYSA-N 1-(2-chlorophenyl)-3-[4-[3-(dimethylamino)propoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=CC=C1Cl AKRRFFJBSRFAKM-UHFFFAOYSA-N 0.000 claims 1
- IQZBUIXIRRPSOX-UHFFFAOYSA-N 1-(3,4-difluorophenyl)-3-[3-(4-fluoro-2-methylpyrazol-3-yl)-4-methoxyphenyl]urea Chemical compound C1=C(C=2N(N=CC=2F)C)C(OC)=CC=C1NC(=O)NC1=CC=C(F)C(F)=C1 IQZBUIXIRRPSOX-UHFFFAOYSA-N 0.000 claims 1
- JOKWIYRWUVIDFP-UHFFFAOYSA-N 1-(3,4-difluorophenyl)-3-[4-[3-(dimethylamino)propoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=C(F)C(F)=C1 JOKWIYRWUVIDFP-UHFFFAOYSA-N 0.000 claims 1
- WUHRMCLLWNDNNN-UHFFFAOYSA-N 1-(3,4-difluorophenyl)-3-[4-methoxy-3-(2-propan-2-ylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C(C)C)C(OC)=CC=C1NC(=O)NC1=CC=C(F)C(F)=C1 WUHRMCLLWNDNNN-UHFFFAOYSA-N 0.000 claims 1
- XJQOBPWUHSCEHB-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[3-(2-methylpyrazol-3-yl)-4-(trifluoromethoxy)phenyl]urea Chemical compound CC(=O)C1=CC=CC(NC(=O)NC=2C=C(C(OC(F)(F)F)=CC=2)C=2N(N=CC=2)C)=C1 XJQOBPWUHSCEHB-UHFFFAOYSA-N 0.000 claims 1
- RZKKRHPYWSDEPC-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[3-(4-bromo-2-methylpyrazol-3-yl)-4-methoxyphenyl]urea Chemical compound C1=C(C=2N(N=CC=2Br)C)C(OC)=CC=C1NC(=O)NC1=CC=CC(C(C)=O)=C1 RZKKRHPYWSDEPC-UHFFFAOYSA-N 0.000 claims 1
- MUVRETPWYFCQEO-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[3-(4-chloro-2-methylpyrazol-3-yl)-4-methoxyphenyl]urea Chemical compound C1=C(C=2N(N=CC=2Cl)C)C(OC)=CC=C1NC(=O)NC1=CC=CC(C(C)=O)=C1 MUVRETPWYFCQEO-UHFFFAOYSA-N 0.000 claims 1
- RQKPEVCOQPQZKJ-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[3-(4-fluoro-2-methylpyrazol-3-yl)-4-methoxyphenyl]urea Chemical compound C1=C(C=2N(N=CC=2F)C)C(OC)=CC=C1NC(=O)NC1=CC=CC(C(C)=O)=C1 RQKPEVCOQPQZKJ-UHFFFAOYSA-N 0.000 claims 1
- KYXMICVUYBQTKO-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[4-[2-(dimethylamino)ethoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCN(C)C)=CC=C1NC(=O)NC1=CC=CC(C(C)=O)=C1 KYXMICVUYBQTKO-UHFFFAOYSA-N 0.000 claims 1
- CBCPHCWQGAIWHN-UHFFFAOYSA-N 1-(3-chloro-4-fluorophenyl)-3-[3-(4-chloro-2-propan-2-ylpyrazol-3-yl)-4-methoxyphenyl]urea Chemical compound C1=C(C=2N(N=CC=2Cl)C(C)C)C(OC)=CC=C1NC(=O)NC1=CC=C(F)C(Cl)=C1 CBCPHCWQGAIWHN-UHFFFAOYSA-N 0.000 claims 1
- HDZVUUPSYJKDLQ-UHFFFAOYSA-N 1-(3-chloro-4-fluorophenyl)-3-[4-[3-(dimethylamino)propoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=C(F)C(Cl)=C1 HDZVUUPSYJKDLQ-UHFFFAOYSA-N 0.000 claims 1
- IYFWAPPLASCWAZ-UHFFFAOYSA-N 1-(3-chloro-4-fluorophenyl)-3-[4-methoxy-3-(2-propan-2-ylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C(C)C)C(OC)=CC=C1NC(=O)NC1=CC=C(F)C(Cl)=C1 IYFWAPPLASCWAZ-UHFFFAOYSA-N 0.000 claims 1
- DYJGPULWLQKPCM-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[3-(4-fluoro-2-methylpyrazol-3-yl)-4-methoxyphenyl]urea Chemical compound C1=C(C=2N(N=CC=2F)C)C(OC)=CC=C1NC(=O)NC1=CC=CC(Cl)=C1 DYJGPULWLQKPCM-UHFFFAOYSA-N 0.000 claims 1
- FUTGUWWRHLXGAA-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[4-[3-(dimethylamino)propoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=CC(Cl)=C1 FUTGUWWRHLXGAA-UHFFFAOYSA-N 0.000 claims 1
- BHXIJWIPHWPWMZ-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[4-methoxy-3-(2-propan-2-ylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C(C)C)C(OC)=CC=C1NC(=O)NC1=CC=CC(Cl)=C1 BHXIJWIPHWPWMZ-UHFFFAOYSA-N 0.000 claims 1
- ZCIGOOKMMMEXLR-UHFFFAOYSA-N 1-(4-bromophenyl)-3-[3-(4-chloro-2-methylpyrazol-3-yl)-4-methoxyphenyl]urea Chemical compound C1=C(C=2N(N=CC=2Cl)C)C(OC)=CC=C1NC(=O)NC1=CC=C(Br)C=C1 ZCIGOOKMMMEXLR-UHFFFAOYSA-N 0.000 claims 1
- HWPJTGZJBXZFTG-UHFFFAOYSA-N 1-(4-bromophenyl)-3-[3-(4-fluoro-2-methylpyrazol-3-yl)-4-methoxyphenyl]urea Chemical compound C1=C(C=2N(N=CC=2F)C)C(OC)=CC=C1NC(=O)NC1=CC=C(Br)C=C1 HWPJTGZJBXZFTG-UHFFFAOYSA-N 0.000 claims 1
- CFZOQPPLVOSFRY-UHFFFAOYSA-N 1-(4-chloro-2-hydroxyphenyl)-3-[3-(4-chloro-2-methylpyrazol-3-yl)-4-[2-(dimethylamino)ethoxy]phenyl]urea Chemical compound C1=C(C=2N(N=CC=2Cl)C)C(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C=C1O CFZOQPPLVOSFRY-UHFFFAOYSA-N 0.000 claims 1
- AAIDILCUIHXJCF-UHFFFAOYSA-N 1-(4-chloro-2-hydroxyphenyl)-3-[4-[2-(dimethylamino)ethoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C=C1O AAIDILCUIHXJCF-UHFFFAOYSA-N 0.000 claims 1
- MUAIQGSPYXXUFM-UHFFFAOYSA-N 1-(4-chloro-2-hydroxyphenyl)-3-[4-[2-(dimethylamino)ethoxy]-3-(4-fluoro-2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2F)C)C(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C=C1O MUAIQGSPYXXUFM-UHFFFAOYSA-N 0.000 claims 1
- KZGMQZNUVWHEBH-UHFFFAOYSA-N 1-(4-chloro-2-hydroxyphenyl)-3-[4-[3-(dimethylamino)propoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C=C1O KZGMQZNUVWHEBH-UHFFFAOYSA-N 0.000 claims 1
- VYLXIDYOEOCWPM-UHFFFAOYSA-N 1-(4-chloro-2-hydroxyphenyl)-3-[4-[3-(dimethylamino)propoxy]-3-(4-fluoro-2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2F)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C=C1O VYLXIDYOEOCWPM-UHFFFAOYSA-N 0.000 claims 1
- QKIPQEPOINCSRI-UHFFFAOYSA-N 1-(4-chloro-3-hydroxyphenyl)-3-[3-(4-chloro-2-methylpyrazol-3-yl)-4-[2-(dimethylamino)ethoxy]phenyl]urea Chemical compound C1=C(C=2N(N=CC=2Cl)C)C(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C(O)=C1 QKIPQEPOINCSRI-UHFFFAOYSA-N 0.000 claims 1
- LQRDYQRJKRTUNV-UHFFFAOYSA-N 1-(4-chloro-3-hydroxyphenyl)-3-[3-(4-chloro-2-methylpyrazol-3-yl)-4-[3-(dimethylamino)propoxy]phenyl]urea Chemical compound C1=C(C=2N(N=CC=2Cl)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C(O)=C1 LQRDYQRJKRTUNV-UHFFFAOYSA-N 0.000 claims 1
- KFRQVCIHYIBIDP-UHFFFAOYSA-N 1-(4-chloro-3-hydroxyphenyl)-3-[4-[2-(dimethylamino)ethoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C(O)=C1 KFRQVCIHYIBIDP-UHFFFAOYSA-N 0.000 claims 1
- SDGMUFKTBUMBSQ-UHFFFAOYSA-N 1-(4-chloro-3-hydroxyphenyl)-3-[4-[2-(dimethylamino)ethoxy]-3-(4-fluoro-2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2F)C)C(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C(O)=C1 SDGMUFKTBUMBSQ-UHFFFAOYSA-N 0.000 claims 1
- HMXOLNVQWNOHGP-UHFFFAOYSA-N 1-(4-chloro-3-hydroxyphenyl)-3-[4-[3-(dimethylamino)propoxy]-3-(2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C(O)=C1 HMXOLNVQWNOHGP-UHFFFAOYSA-N 0.000 claims 1
- AJCHXXIUIJVVTL-UHFFFAOYSA-N 1-(4-chloro-3-hydroxyphenyl)-3-[4-[3-(dimethylamino)propoxy]-3-(4-fluoro-2-methylpyrazol-3-yl)phenyl]urea Chemical compound C1=C(C=2N(N=CC=2F)C)C(OCCCN(C)C)=CC=C1NC(=O)NC1=CC=C(Cl)C(O)=C1 AJCHXXIUIJVVTL-UHFFFAOYSA-N 0.000 claims 1
- PRXZJWYJIDOHSL-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[3-(2-methylpyrazol-3-yl)-4-(trifluoromethoxy)phenyl]urea Chemical compound CN1N=CC=C1C1=CC(NC(=O)NC=2C=CC(Cl)=CC=2)=CC=C1OC(F)(F)F PRXZJWYJIDOHSL-UHFFFAOYSA-N 0.000 claims 1
- UDHJBPYYBAFWGS-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[3-(4-chloro-2-propan-2-ylpyrazol-3-yl)-4-methoxyphenyl]urea Chemical compound C1=C(C=2N(N=CC=2Cl)C(C)C)C(OC)=CC=C1NC(=O)NC1=CC=C(Cl)C=C1 UDHJBPYYBAFWGS-UHFFFAOYSA-N 0.000 claims 1
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| HRP20060100T3 (en) | 2003-07-22 | 2007-03-31 | Arena Pharmaceuticals Inc | Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related thereto |
| CN1926114B (zh) * | 2004-03-23 | 2011-08-24 | 艾尼纳制药公司 | 用于制备经取代n-芳基-n′-′3-(1h-吡唑-5-基)苯基脲及其中间体的方法 |
| SA05260357B1 (ar) | 2004-11-19 | 2008-09-08 | ارينا فارماسيتو تيكالز ، أنك | مشتقات 3_فينيل_بيرازول كمعدلات لمستقبل سيروتينين 5_ht2a مفيدة في علاج الاضطرابات المتعلقه به |
| JP2008523071A (ja) | 2004-12-07 | 2008-07-03 | ルーカス ファーマシューティカルズ, インコーポレイテッド | Mapキナーゼの尿素インヒビター |
| CA2621152A1 (en) * | 2005-09-29 | 2007-04-12 | Arena Pharmaceuticals, Inc. | Pharmaceutical compositions of a 5-ht2a serotonin receptor modulator useful for the treatment of disorders related thereto |
| CA2646076C (en) | 2006-05-18 | 2015-06-30 | Arena Pharmaceuticals, Inc. | Ethers, secondary amines and derivatives thereof as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto |
| WO2007136689A2 (en) | 2006-05-18 | 2007-11-29 | Arena Pharmaceuticals, Inc. | Crystalline forms and processes for the preparation of phenyl-pyrazoles useful as modulators of the 5-ht2a serotonin receptor |
| USRE45336E1 (en) | 2006-05-18 | 2015-01-13 | Arena Pharmaceuticals, Inc. | Primary amines and derivatives thereof as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto |
| TWI415845B (zh) | 2006-10-03 | 2013-11-21 | Arena Pharm Inc | 用於治療與5-ht2a血清素受體相關聯病症之作為5-ht2a血清素受體之調節劑的吡唑衍生物 |
| EP2190844B3 (en) | 2007-08-15 | 2013-07-17 | Arena Pharmaceuticals, Inc. | Imidazo[1,2-a]pyridine derivatives as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto |
| WO2009123714A2 (en) * | 2008-04-02 | 2009-10-08 | Arena Pharmaceuticals, Inc. | Processes for the preparation of pyrazole derivatives useful as modulators of the 5-ht2a serotonin receptor |
| WO2010019930A1 (en) * | 2008-08-15 | 2010-02-18 | Locus Pharmaceuticals, Inc. | Urea derivatives as inhibitors of map kinases |
| TR201805216T4 (en) | 2008-10-28 | 2018-06-21 | Arena Pharm Inc | COMPOSITIONS OF A USEFUL 5-HT2A SEROTONINE RECEPTOR MODULATOR FOR THE TREATMENT OF RELATED DISORDERS |
| WO2010062321A1 (en) | 2008-10-28 | 2010-06-03 | Arena Pharmaceuticals, Inc. | Processes useful for the preparation of 1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea and crystalline forms related thereto |
| WO2011075596A1 (en) | 2009-12-18 | 2011-06-23 | Arena Pharmaceuticals, Inc. | Crystalline forms of certain 3-phenyl-pyrazole derivatives as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto |
| US8461179B1 (en) | 2012-06-07 | 2013-06-11 | Deciphera Pharmaceuticals, Llc | Dihydronaphthyridines and related compounds useful as kinase inhibitors for the treatment of proliferative diseases |
| JP2018516992A (ja) | 2015-06-12 | 2018-06-28 | アクソファント サイエンシーズ ゲーエムベーハーAxovant Sciences Gmbh | レム睡眠行動障害の予防および処置のために有用なジアリールおよびアリールヘテロアリール尿素誘導体 |
| WO2017011767A2 (en) | 2015-07-15 | 2017-01-19 | Axovant Sciences Ltd. | Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of hallucinations associated with a neurodegenerative disease |
| JP7523351B2 (ja) | 2018-01-31 | 2024-07-26 | デシフェラ・ファーマシューティカルズ,エルエルシー | 肥満細胞症の治療のための併用療法 |
| JP2021512105A (ja) | 2018-01-31 | 2021-05-13 | デシフェラ・ファーマシューティカルズ,エルエルシー | 消化管間質腫瘍の治療のための併用療法 |
| NZ784949A (en) | 2019-08-12 | 2025-09-26 | Deciphera Pharmaceuticals Llc | Ripretinib for treating gastrointestinal stromal tumors |
| TWI878335B (zh) | 2019-08-12 | 2025-04-01 | 美商迪賽孚爾製藥有限公司 | 治療胃腸道基質瘤方法 |
| NZ789199A (en) | 2019-12-30 | 2025-07-25 | Deciphera Pharmaceuticals Llc | Compositions of 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea |
| AU2020419197B2 (en) | 2019-12-30 | 2023-08-31 | Deciphera Pharmaceuticals, Llc | Amorphous kinase inhibitor formulations and methods of use thereof |
| CN113855784B (zh) * | 2021-09-26 | 2025-04-15 | 深圳辰扬生物科技有限公司 | 多肽的抗抑郁、抗焦虑用途及复合体 |
| US11779572B1 (en) | 2022-09-02 | 2023-10-10 | Deciphera Pharmaceuticals, Llc | Methods of treating gastrointestinal stromal tumors |
| CN120359211A (zh) | 2022-12-08 | 2025-07-22 | 盐野义制药株式会社 | 具有血清素受体结合活性的含氮杂环和碳环衍生物 |
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| US4099012A (en) * | 1975-08-28 | 1978-07-04 | Ciba-Geigy Corporation | 2-pyrazolyl-benzophenones |
| DE2928485A1 (de) * | 1979-07-14 | 1981-01-29 | Bayer Ag | Verwendung von harnstoffderivaten als arzneimittel bei der behandlung von fettstoffwechselstoerungen |
| US4985352A (en) * | 1988-02-29 | 1991-01-15 | The Trustees Of Columbia University In The City Of New York | DNA encoding serotonin 1C (5HT1c) receptor, isolated 5HT1c receptor, mammalian cells expressing same and uses thereof |
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| US5128351A (en) * | 1990-05-04 | 1992-07-07 | American Cyanamid Company | Bis-aryl amide and urea antagonists of platelet activating factor |
| US5077409A (en) * | 1990-05-04 | 1991-12-31 | American Cyanamid Company | Method of preparing bis-aryl amide and urea antagonists of platelet activating factor |
| FR2682379B1 (fr) * | 1991-10-09 | 1994-02-11 | Rhone Poulenc Agrochimie | Nouveaux phenylpyrazoles fongicides. |
| FR2690440B1 (fr) * | 1992-04-27 | 1995-05-19 | Rhone Poulenc Agrochimie | Arylpyrazoles fongicides. |
| EP0714389B1 (en) * | 1993-08-20 | 1998-06-17 | Smithkline Beecham Plc | Amide and urea derivatives as 5ht1d receptor antagonists |
| CZ294097B6 (cs) * | 1995-02-02 | 2004-10-13 | Smithklineábeechamáplc | Indolový derivátŹ způsob jeho přípravy a farmaceutická kompozice s jeho obsahem |
| JPH11503110A (ja) * | 1995-02-17 | 1999-03-23 | スミスクライン・ビーチャム・コーポレイション | Il−8受容体拮抗剤 |
| US6054472A (en) * | 1996-04-23 | 2000-04-25 | Vertex Pharmaceuticals, Incorporated | Inhibitors of IMPDH enzyme |
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| US6541209B1 (en) * | 1997-04-14 | 2003-04-01 | Arena Pharmaceuticals, Inc. | Non-endogenous, constitutively activated human serotonin receptors and small molecule modulators thereof |
| CA2303848C (en) * | 1997-10-31 | 2008-09-30 | Rhone-Poulenc Rorer Limited | Substituted anilides |
| US7517880B2 (en) * | 1997-12-22 | 2009-04-14 | Bayer Pharmaceuticals Corporation | Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas |
| JP2003514763A (ja) * | 1998-04-14 | 2003-04-22 | アリーナ・フアーマシユーチカルズ・インコーポレーテツド | 非内在性の構成的に活性化されるヒトセロトニンレセプターおよびその小分子調節物質 |
| US6140509A (en) * | 1998-06-26 | 2000-10-31 | Arena Pharmaceuticals, Inc. | Non-endogenous, constitutively activated human serotonin receptors and small molecule modulators thereof |
| GB9816263D0 (en) * | 1998-07-24 | 1998-09-23 | Merck Sharp & Dohme | Therapeutic agents |
| CN1263733C (zh) * | 1998-10-22 | 2006-07-12 | 神经研究公司 | 取代苯基衍生物,它们的制备和用途 |
| US6150393A (en) * | 1998-12-18 | 2000-11-21 | Arena Pharmaceuticals, Inc. | Small molecule modulators of non-endogenous, constitutively activated human serotonin receptors |
| FR2810979B1 (fr) * | 2000-06-29 | 2002-08-23 | Adir | Nouveaux derives de diphenyluree, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
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| AU2006206687A1 (en) | 2006-07-27 |
| EP1843762A1 (en) | 2007-10-17 |
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