JP2010514751A - オレキシン受容体拮抗薬としての2−アザ−ビシクロ[3.1.0]ヘキサン誘導体 - Google Patents
オレキシン受容体拮抗薬としての2−アザ−ビシクロ[3.1.0]ヘキサン誘導体 Download PDFInfo
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- JP2010514751A JP2010514751A JP2009543566A JP2009543566A JP2010514751A JP 2010514751 A JP2010514751 A JP 2010514751A JP 2009543566 A JP2009543566 A JP 2009543566A JP 2009543566 A JP2009543566 A JP 2009543566A JP 2010514751 A JP2010514751 A JP 2010514751A
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- JP
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- Prior art keywords
- thiazole
- aza
- bicyclo
- methyl
- carboxylic acid
- Prior art date
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- WSSDGZWSPMAECX-UHFFFAOYSA-N 2-azabicyclo[3.1.0]hexane Chemical class C1CNC2CC21 WSSDGZWSPMAECX-UHFFFAOYSA-N 0.000 title abstract description 11
- 229940123730 Orexin receptor antagonist Drugs 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 94
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 8
- 239000000126 substance Substances 0.000 claims abstract description 5
- -1 2,3-dihydro-benzofuranyl- Chemical group 0.000 claims description 373
- 125000001424 substituent group Chemical group 0.000 claims description 152
- 125000000217 alkyl group Chemical group 0.000 claims description 108
- 125000000623 heterocyclic group Chemical group 0.000 claims description 80
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 73
- 229910052736 halogen Inorganic materials 0.000 claims description 68
- 150000002367 halogens Chemical class 0.000 claims description 68
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 64
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 238000004519 manufacturing process Methods 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 28
- 208000035475 disorder Diseases 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 208000002193 Pain Diseases 0.000 claims description 20
- 208000011580 syndromic disease Diseases 0.000 claims description 19
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- QRDZFPUVLYEQTA-UHFFFAOYSA-N quinoline-8-carboxylic acid Chemical compound C1=CN=C2C(C(=O)O)=CC=CC2=C1 QRDZFPUVLYEQTA-UHFFFAOYSA-N 0.000 claims description 17
- VSQMBZXCDDTZAF-UHFFFAOYSA-N 6-methylimidazo[2,1-b][1,3]thiazole-5-carboxylic acid Chemical compound S1C=CN2C(C(O)=O)=C(C)N=C21 VSQMBZXCDDTZAF-UHFFFAOYSA-N 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 14
- 230000036407 pain Effects 0.000 claims description 14
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- 238000011282 treatment Methods 0.000 claims description 14
- VCLSWKVAHAJSFL-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=CC=C2C(=O)O VCLSWKVAHAJSFL-UHFFFAOYSA-N 0.000 claims description 13
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 206010022437 insomnia Diseases 0.000 claims description 13
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
- 102000002512 Orexin Human genes 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 108060005714 orexin Proteins 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- CHDSHBWEGSCEDX-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1CCO2 CHDSHBWEGSCEDX-UHFFFAOYSA-N 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000000335 thiazolyl group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 8
- 230000004064 dysfunction Effects 0.000 claims description 8
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 claims description 8
- SMBZJSVIKJMSFP-UHFFFAOYSA-N trifluoromethyl hypofluorite Chemical compound FOC(F)(F)F SMBZJSVIKJMSFP-UHFFFAOYSA-N 0.000 claims description 8
- VPYXATIIMHQAPR-UHFFFAOYSA-N 1,2-benzoxazole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NOC2=C1 VPYXATIIMHQAPR-UHFFFAOYSA-N 0.000 claims description 7
- AVBKMSSLAIKOGM-UHFFFAOYSA-N 4-methoxyquinoline-2-carboxylic acid Chemical compound C1=CC=C2C(OC)=CC(C(O)=O)=NC2=C1 AVBKMSSLAIKOGM-UHFFFAOYSA-N 0.000 claims description 7
- 208000012902 Nervous system disease Diseases 0.000 claims description 7
- 208000025966 Neurological disease Diseases 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 208000010877 cognitive disease Diseases 0.000 claims description 7
- 230000003340 mental effect Effects 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- JHTQTAYWCUAENJ-UHFFFAOYSA-N 1,3-benzoxazole-7-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1OC=N2 JHTQTAYWCUAENJ-UHFFFAOYSA-N 0.000 claims description 6
- IJEUISLJVBUNRE-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C)=C1C(O)=O IJEUISLJVBUNRE-UHFFFAOYSA-N 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 6
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 6
- 206010047700 Vomiting Diseases 0.000 claims description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 6
- 235000021271 drinking Nutrition 0.000 claims description 6
- 230000035622 drinking Effects 0.000 claims description 6
- ZGIABSKPSCMXFD-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole-5-carboxylic acid Chemical compound S1C=CN2C(C(=O)O)=CN=C21 ZGIABSKPSCMXFD-UHFFFAOYSA-N 0.000 claims description 6
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 6
- 208000004296 neuralgia Diseases 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 208000019116 sleep disease Diseases 0.000 claims description 6
- 230000008673 vomiting Effects 0.000 claims description 6
- XYRXQPDMBJNYIU-UHFFFAOYSA-N 1,2-dimethylindole-3-carboxylic acid Chemical compound C1=CC=C2N(C)C(C)=C(C(O)=O)C2=C1 XYRXQPDMBJNYIU-UHFFFAOYSA-N 0.000 claims description 5
- BHXVYTQDWMQVBI-UHFFFAOYSA-N 1h-indazole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NNC2=C1 BHXVYTQDWMQVBI-UHFFFAOYSA-N 0.000 claims description 5
- QRWZFUBHOQWUGH-UHFFFAOYSA-N 2,5-dimethylpyrazole-3-carboxylic acid Chemical compound CC=1C=C(C(O)=O)N(C)N=1 QRWZFUBHOQWUGH-UHFFFAOYSA-N 0.000 claims description 5
- OYOMMXTUBZYEGS-UHFFFAOYSA-N 3-methylimidazo[2,1-b][1,3]thiazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)N2C(C)=CSC2=N1 OYOMMXTUBZYEGS-UHFFFAOYSA-N 0.000 claims description 5
- 208000030814 Eating disease Diseases 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 5
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 235000014632 disordered eating Nutrition 0.000 claims description 5
- 235000005686 eating Nutrition 0.000 claims description 5
- 230000007937 eating Effects 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 229940001470 psychoactive drug Drugs 0.000 claims description 5
- 239000004089 psychotropic agent Substances 0.000 claims description 5
- SWVBPJMJJQONPB-UHFFFAOYSA-N pyrrolo[2,1-b][1,3]thiazole-7-carboxylic acid Chemical compound C1=CSC2=C(C(=O)O)C=CN21 SWVBPJMJJQONPB-UHFFFAOYSA-N 0.000 claims description 5
- ORSZGLLQNYSMNO-UHFFFAOYSA-N 1,3-benzothiazole-7-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1SC=N2 ORSZGLLQNYSMNO-UHFFFAOYSA-N 0.000 claims description 4
- DTJLXXLXQPOQBZ-UHFFFAOYSA-N 1-ethyl-3-methylpyrazole-4-carboxylic acid Chemical compound CCN1C=C(C(O)=O)C(C)=N1 DTJLXXLXQPOQBZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000850 2H-chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- QMVZMKJWEQFJDP-UHFFFAOYSA-N 2h-chromene-5-carboxylic acid Chemical compound O1CC=CC2=C1C=CC=C2C(=O)O QMVZMKJWEQFJDP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
- ZGWGSEUMABQEMD-UHFFFAOYSA-N 4-methyl-1,3-thiazole-5-carboxylic acid Chemical compound CC=1N=CSC=1C(O)=O ZGWGSEUMABQEMD-UHFFFAOYSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000000044 Amnesia Diseases 0.000 claims description 4
- 208000031091 Amnestic disease Diseases 0.000 claims description 4
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- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 208000012661 Dyskinesia Diseases 0.000 claims description 4
- 208000004454 Hyperalgesia Diseases 0.000 claims description 4
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- 208000005793 Restless legs syndrome Diseases 0.000 claims description 4
- 206010046543 Urinary incontinence Diseases 0.000 claims description 4
- 230000006986 amnesia Effects 0.000 claims description 4
- 230000037005 anaesthesia Effects 0.000 claims description 4
- 235000019789 appetite Nutrition 0.000 claims description 4
- 230000036528 appetite Effects 0.000 claims description 4
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 230000002267 hypothalamic effect Effects 0.000 claims description 4
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- XBFRQODQXBMILB-UHFFFAOYSA-N 1,3-benzothiazole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1N=CS2 XBFRQODQXBMILB-UHFFFAOYSA-N 0.000 claims description 3
- YDGHXEVBZZGFLL-KPFFTGBYSA-N 1-ethyl-n-[[(1s,3s,5s)-2-[5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3-methylpyrazole-4-carboxamide Chemical compound CC1=NN(CC)C=C1C(=O)NC[C@H]1N(C(=O)C2=C(SC(C)=N2)C=2C=C(F)C=CC=2)[C@H]2C[C@H]2C1 YDGHXEVBZZGFLL-KPFFTGBYSA-N 0.000 claims description 3
- ZVXXYWHMRDJFDL-HFTRVMKXSA-N 2,2-difluoro-n-[[(1s,3s,5s)-2-[5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1,3-benzodioxole-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OC(F)(F)OC=3C=CC=2)=C1C1=CC=CC(F)=C1 ZVXXYWHMRDJFDL-HFTRVMKXSA-N 0.000 claims description 3
- ISNGGIADAFLJMJ-NEWSRXKRSA-N 2-ethyl-n-[[(1s,3s,5s)-2-[5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-5-methylpyrazole-3-carboxamide Chemical compound CCN1N=C(C)C=C1C(=O)NC[C@H]1N(C(=O)C2=C(SC(C)=N2)C=2C=C(F)C=CC=2)[C@H]2C[C@H]2C1 ISNGGIADAFLJMJ-NEWSRXKRSA-N 0.000 claims description 3
- KDPOFQJHFWJFCB-UHFFFAOYSA-N 2-methyl-1,3-benzoxazole-7-carboxylic acid Chemical compound C1=CC(C(O)=O)=C2OC(C)=NC2=C1 KDPOFQJHFWJFCB-UHFFFAOYSA-N 0.000 claims description 3
- SQVZFICXVOEKNL-WVBUVRCRSA-N 5-fluoro-n-[[(1s,3s,5s)-2-[5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1h-indole-2-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2NC3=CC=C(F)C=C3C=2)=C1C1=CC=CC(F)=C1 SQVZFICXVOEKNL-WVBUVRCRSA-N 0.000 claims description 3
- BZHUUDQQILZKGO-JJXUHFIVSA-N 6-fluoro-n-[[(1s,3s,5s)-2-[5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-4h-1,3-benzodioxine-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OCOCC=3C=C(F)C=2)=C1C1=CC=CC(F)=C1 BZHUUDQQILZKGO-JJXUHFIVSA-N 0.000 claims description 3
- GVOZOHSZUJYIQL-UHFFFAOYSA-N 7-chloro-1-benzofuran-4-carboxylic acid Chemical compound OC(=O)C1=CC=C(Cl)C2=C1C=CO2 GVOZOHSZUJYIQL-UHFFFAOYSA-N 0.000 claims description 3
- KELIAGSOLXPTAY-UHFFFAOYSA-N 7-fluoro-1-benzofuran-4-carboxylic acid Chemical compound OC(=O)C1=CC=C(F)C2=C1C=CO2 KELIAGSOLXPTAY-UHFFFAOYSA-N 0.000 claims description 3
- OPXMVZLSLQAXPQ-MMOPVJDHSA-N 7-fluoro-n-[[(1s,3s,5s)-2-[5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1h-indole-2-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2NC3=C(F)C=CC=C3C=2)=C1C1=CC=CC(F)=C1 OPXMVZLSLQAXPQ-MMOPVJDHSA-N 0.000 claims description 3
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- 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 claims description 3
- FGCNGGNPMHRAGA-UZEJHQAJSA-N n-[[(1s,3s,5s)-2-[2-(2-fluorophenyl)benzoyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1-benzofuran-4-carboxamide Chemical compound FC1=CC=CC=C1C1=CC=CC=C1C(=O)N1[C@H](CNC(=O)C=2C=3C=COC=3C=CC=2)C[C@@H]2C[C@@H]21 FGCNGGNPMHRAGA-UZEJHQAJSA-N 0.000 claims description 3
- UHINWWWQPPBTFJ-AOUJKTHWSA-N n-[[(1s,3s,5s)-2-[2-(3-chlorophenyl)benzoyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1-benzofuran-4-carboxamide Chemical compound ClC1=CC=CC(C=2C(=CC=CC=2)C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3C=COC=3C=CC=2)=C1 UHINWWWQPPBTFJ-AOUJKTHWSA-N 0.000 claims description 3
- PYBMNLHPXNANJX-PVAVHDDUSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1,3,5-trimethylpyrazole-4-carboxamide Chemical compound CC1=NN(C)C(C)=C1C(=O)NC[C@H]1N(C(=O)C2=C(SC(N)=N2)C=2C=C(F)C=CC=2)[C@H]2C[C@H]2C1 PYBMNLHPXNANJX-PVAVHDDUSA-N 0.000 claims description 3
- ZRNCUSLODZTAGF-KMFMINBZSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1,3-benzodioxole-4-carboxamide Chemical compound S1C(N)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OCOC=3C=CC=2)=C1C1=CC=CC(F)=C1 ZRNCUSLODZTAGF-KMFMINBZSA-N 0.000 claims description 3
- FBKAZYQXMOLMMU-HFTRVMKXSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1-ethyl-3-methylpyrazole-4-carboxamide Chemical compound CC1=NN(CC)C=C1C(=O)NC[C@H]1N(C(=O)C2=C(SC(N)=N2)C=2C=C(F)C=CC=2)[C@H]2C[C@H]2C1 FBKAZYQXMOLMMU-HFTRVMKXSA-N 0.000 claims description 3
- UDPYNUNNSFKAGE-KUDFPVQQSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1-methylindole-3-carboxamide Chemical compound N1([C@H]2C[C@H]2C[C@H]1CNC(=O)C1=CN(C2=CC=CC=C21)C)C(=O)C=1N=C(N)SC=1C1=CC=CC(F)=C1 UDPYNUNNSFKAGE-KUDFPVQQSA-N 0.000 claims description 3
- FSJQWDJNMKMWGA-HFTRVMKXSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound S1C(N)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OCCOC=3C=CC=2)=C1C1=CC=CC(F)=C1 FSJQWDJNMKMWGA-HFTRVMKXSA-N 0.000 claims description 3
- CJTMBFBFOHCHNN-ALKREAHSSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(N)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=CC(F)=C1 CJTMBFBFOHCHNN-ALKREAHSSA-N 0.000 claims description 3
- SXOUZMVBNPCWIL-KBMXLJTQSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,5-dimethyl-1,3-oxazole-4-carboxamide Chemical compound O1C(C)=NC(C(=O)NC[C@H]2N([C@H]3C[C@H]3C2)C(=O)C2=C(SC(N)=N2)C=2C=C(F)C=CC=2)=C1C SXOUZMVBNPCWIL-KBMXLJTQSA-N 0.000 claims description 3
- FFWZFLVTHJRBRH-PVAVHDDUSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2-ethyl-5-methylpyrazole-3-carboxamide Chemical compound CCN1N=C(C)C=C1C(=O)NC[C@H]1N(C(=O)C2=C(SC(N)=N2)C=2C=C(F)C=CC=2)[C@H]2C[C@H]2C1 FFWZFLVTHJRBRH-PVAVHDDUSA-N 0.000 claims description 3
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- RIVJJZYVIMDNKH-INWMFGNUSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,2-difluoro-1,3-benzodioxole-4-carboxamide Chemical compound S1C(N)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OC(F)(F)OC=3C=CC=2)=C1C1=CC=CC(F)=C1 RIVJJZYVIMDNKH-INWMFGNUSA-N 0.000 claims description 2
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- IHBNXFCVHGTHKD-KBMXLJTQSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,5-dimethylpyrazole-3-carboxamide Chemical compound CN1N=C(C)C=C1C(=O)NC[C@H]1N(C(=O)C2=C(SC(N)=N2)C=2C=C(F)C=CC=2)[C@H]2C[C@H]2C1 IHBNXFCVHGTHKD-KBMXLJTQSA-N 0.000 claims description 2
- GWZRHORPTRIYPH-KBMXLJTQSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2-methylimidazo[2,1-b][1,3]thiazole-5-carboxamide Chemical compound N1([C@H]2C[C@H]2C[C@H]1CNC(=O)C=1N2C=C(SC2=NC=1)C)C(=O)C=1N=C(N)SC=1C1=CC=CC(F)=C1 GWZRHORPTRIYPH-KBMXLJTQSA-N 0.000 claims description 2
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- ZCPJOEXFIVNBSM-KBMXLJTQSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3-methylimidazo[2,1-b][1,3]thiazole-2-carboxamide Chemical compound N1([C@H]2C[C@H]2C[C@H]1CNC(=O)C1=C(N2C=CN=C2S1)C)C(=O)C=1N=C(N)SC=1C1=CC=CC(F)=C1 ZCPJOEXFIVNBSM-KBMXLJTQSA-N 0.000 claims description 2
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- YGIUUAOPOXXRJV-KPFFTGBYSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]isoquinoline-1-carboxamide Chemical compound S1C(N)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=CC=CC=C3C=CN=2)=C1C1=CC=CC(F)=C1 YGIUUAOPOXXRJV-KPFFTGBYSA-N 0.000 claims description 2
- FQQGWKSSBLQNSB-MMOPVJDHSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]isoquinoline-5-carboxamide Chemical compound S1C(N)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=CC=NC=C3C=CC=2)=C1C1=CC=CC(F)=C1 FQQGWKSSBLQNSB-MMOPVJDHSA-N 0.000 claims description 2
- GYNSFMRWLPIVJD-KUDFPVQQSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-4-carboxamide Chemical compound S1C(N)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=CC=CC=C3N=CC=2)=C1C1=CC=CC(F)=C1 GYNSFMRWLPIVJD-KUDFPVQQSA-N 0.000 claims description 2
- JKHPJPIOIGQUSW-KUDFPVQQSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-5-carboxamide Chemical compound S1C(N)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=CC=CN=C3C=CC=2)=C1C1=CC=CC(F)=C1 JKHPJPIOIGQUSW-KUDFPVQQSA-N 0.000 claims description 2
- ICZOTUOVKVXDJS-KPFFTGBYSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-8-carboxamide Chemical compound S1C(N)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=NC=CC=C3C=CC=2)=C1C1=CC=CC(F)=C1 ICZOTUOVKVXDJS-KPFFTGBYSA-N 0.000 claims description 2
- BJUAUMKZWDEZAL-UWVAXJGDSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1-benzofuran-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N)S2)C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3C=COC=3C=CC=2)=C1 BJUAUMKZWDEZAL-UWVAXJGDSA-N 0.000 claims description 2
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- JRPGUYFEQYSWLH-AOIWGVFYSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N)S2)C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OCCOC=3C=CC=2)=C1 JRPGUYFEQYSWLH-AOIWGVFYSA-N 0.000 claims description 2
- NDWOXJJCWNRPHY-UWVAXJGDSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N)S2)C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCOC=3C=CC=2)=C1 NDWOXJJCWNRPHY-UWVAXJGDSA-N 0.000 claims description 2
- LIELRRIIARUVHU-HBFSDRIKSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-7-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N)S2)C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OCCC=3C=CC=2)=C1 LIELRRIIARUVHU-HBFSDRIKSA-N 0.000 claims description 2
- QRJBVPFDEZXYFL-PMPSAXMXSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydrothieno[3,4-b][1,4]dioxine-5-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N)S2)C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C2=C3OCCOC3=CS2)=C1 QRJBVPFDEZXYFL-PMPSAXMXSA-N 0.000 claims description 2
- CMNKWJKYFWEVJN-AOIWGVFYSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3,4-dihydro-2h-1,4-benzoxazine-5-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N)S2)C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3NCCOC=3C=CC=2)=C1 CMNKWJKYFWEVJN-AOIWGVFYSA-N 0.000 claims description 2
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- SMSKKKDQSPQPBB-HKBOAZHASA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3-ethynylbenzamide Chemical compound CC1=CC=CC(C2=C(N=C(N)S2)C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=C(C=CC=2)C#C)=C1 SMSKKKDQSPQPBB-HKBOAZHASA-N 0.000 claims description 2
- SFSKTVHOJFMXIW-HBFSDRIKSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3-methylsulfanylbenzamide Chemical compound CSC1=CC=CC(C(=O)NC[C@H]2N([C@H]3C[C@H]3C2)C(=O)C2=C(SC(N)=N2)C=2C=C(C)C=CC=2)=C1 SFSKTVHOJFMXIW-HBFSDRIKSA-N 0.000 claims description 2
- DWTJVHUMWXCHJZ-IKGGRYGDSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-6-methylimidazo[2,1-b][1,3]thiazole-5-carboxamide Chemical compound N1([C@H]2C[C@H]2C[C@H]1CNC(=O)C=1N2C=CSC2=NC=1C)C(=O)C=1N=C(N)SC=1C1=CC=CC(C)=C1 DWTJVHUMWXCHJZ-IKGGRYGDSA-N 0.000 claims description 2
- YLKCKZJWYQIFJX-DYXWJJEUSA-N n-[[(1s,3s,5s)-2-[2-amino-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-8-carboxamide Chemical compound CC1=CC=CC(C2=C(N=C(N)S2)C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=NC=CC=C3C=CC=2)=C1 YLKCKZJWYQIFJX-DYXWJJEUSA-N 0.000 claims description 2
- DGPQYYMFHNHJFI-JLHGSKIFSA-N n-[[(1s,3s,5s)-2-[2-cyclopropyl-5-(2-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound FC1=CC=CC=C1C1=C(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCOC=3C=CC=2)N=C(C2CC2)S1 DGPQYYMFHNHJFI-JLHGSKIFSA-N 0.000 claims description 2
- HLQLEGQHWVBEPG-LZNRXBQRSA-N n-[[(1s,3s,5s)-2-[2-cyclopropyl-5-(4-fluorophenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound C1=CC(F)=CC=C1C1=C(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCOC=3C=CC=2)N=C(C2CC2)S1 HLQLEGQHWVBEPG-LZNRXBQRSA-N 0.000 claims description 2
- YLLSWNPZCFUPRS-LZNRXBQRSA-N n-[[(1s,3s,5s)-2-[2-cyclopropyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound FC(F)(F)C1=CC=CC(C2=C(N=C(S2)C2CC2)C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCOC=3C=CC=2)=C1 YLLSWNPZCFUPRS-LZNRXBQRSA-N 0.000 claims description 2
- VJJRTFROQVBXHH-DXIQSLLYSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3C=COC=3C=CC=2)=C1C1=CC=CC(C)=C1 VJJRTFROQVBXHH-DXIQSLLYSA-N 0.000 claims description 2
- OLFCCRPHCVZQSG-DYXWJJEUSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OCCOC=3C=CC=2)=C1C1=CC=CC(C)=C1 OLFCCRPHCVZQSG-DYXWJJEUSA-N 0.000 claims description 2
- KCOANUKFVBJCKP-DXIQSLLYSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=CC(C)=C1 KCOANUKFVBJCKP-DXIQSLLYSA-N 0.000 claims description 2
- ZUGBKCDIFFBUIC-SQNIBIBYSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydrothieno[3,4-b][1,4]dioxine-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C2=C3OCCOC3=CS2)=C1C1=CC=CC(C)=C1 ZUGBKCDIFFBUIC-SQNIBIBYSA-N 0.000 claims description 2
- PEALOQZNTJHOHY-DYXWJJEUSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3,4-dihydro-2h-1,4-benzoxazine-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3NCCOC=3C=CC=2)=C1C1=CC=CC(C)=C1 PEALOQZNTJHOHY-DYXWJJEUSA-N 0.000 claims description 2
- PBTITHPDWJGISI-QTEQDKRBSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3,4-dihydro-2h-chromene-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCCOC=3C=CC=2)=C1C1=CC=CC(C)=C1 PBTITHPDWJGISI-QTEQDKRBSA-N 0.000 claims description 2
- GCMSAOJERLBESS-GIWBLDEGSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3,4-dihydro-2h-chromene-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OCCCC=3C=CC=2)=C1C1=CC=CC(C)=C1 GCMSAOJERLBESS-GIWBLDEGSA-N 0.000 claims description 2
- SINYBNKIDPMQMD-GIVPXCGWSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H]1C[C@@H]2C[C@@H]2N1C(=O)C=1N=C(SC=1C=1C=C(C)C=CC=1)C)NC(=O)C1=CC=CC(C(F)(F)F)=C1 SINYBNKIDPMQMD-GIVPXCGWSA-N 0.000 claims description 2
- ATVUJFCDAHNQKA-IKGGRYGDSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-6-(trifluoromethyl)imidazo[2,1-b][1,3]thiazole-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2N3C=CSC3=NC=2C(F)(F)F)=C1C1=CC=CC(C)=C1 ATVUJFCDAHNQKA-IKGGRYGDSA-N 0.000 claims description 2
- YQDLDJGYDZSKNF-GIWBLDEGSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]isoquinoline-1-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=CC=CC=C3C=CN=2)=C1C1=CC=CC(C)=C1 YQDLDJGYDZSKNF-GIWBLDEGSA-N 0.000 claims description 2
- TUYNRWXGOHLKKD-DPLHUUCSSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-2-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2N=C3C=CC=CC3=CC=2)=C1C1=CC=CC(C)=C1 TUYNRWXGOHLKKD-DPLHUUCSSA-N 0.000 claims description 2
- HKBPOHZBBPDWEE-GIWBLDEGSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=NC=CC=C3C=CC=2)=C1C1=CC=CC(C)=C1 HKBPOHZBBPDWEE-GIWBLDEGSA-N 0.000 claims description 2
- CDJYZBZDMPVNPM-XFQAVAEZSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-[2-(trifluoromethyl)phenyl]-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3C=COC=3C=CC=2)=C1C1=CC=CC=C1C(F)(F)F CDJYZBZDMPVNPM-XFQAVAEZSA-N 0.000 claims description 2
- LRBPYXXOWQPIQY-CBQOVEMMSA-N n-[[(1s,3s,5s)-2-[2-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=NC=CC=C3C=CC=2)=C1C1=CC=CC(C(F)(F)F)=C1 LRBPYXXOWQPIQY-CBQOVEMMSA-N 0.000 claims description 2
- KJGPKBFNTWFXIY-WWMYMODYSA-N n-[[(1s,3s,5s)-2-[5-(2,3-dichlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=NC=CC=C3C=CC=2)=C1C1=CC=CC(Cl)=C1Cl KJGPKBFNTWFXIY-WWMYMODYSA-N 0.000 claims description 2
- GFZBQTVLLBULSP-DPLHUUCSSA-N n-[[(1s,3s,5s)-2-[5-(2,3-dimethylphenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=NC=CC=C3C=CC=2)=C1C1=CC=CC(C)=C1C GFZBQTVLLBULSP-DPLHUUCSSA-N 0.000 claims description 2
- RRLLDPBLZSIRIN-GJYPPUQNSA-N n-[[(1s,3s,5s)-2-[5-(3,4-dichlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2N3C=CC=CC3=NC=2)=C1C1=CC=C(Cl)C(Cl)=C1 RRLLDPBLZSIRIN-GJYPPUQNSA-N 0.000 claims description 2
- IRKPOWMQKJCWJT-FGSXEWAUSA-N n-[[(1s,3s,5s)-2-[5-(3,4-dichlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=NC=CC=C3C=CC=2)=C1C1=CC=C(Cl)C(Cl)=C1 IRKPOWMQKJCWJT-FGSXEWAUSA-N 0.000 claims description 2
- RZISYTTYCMGRIV-XFQAVAEZSA-N n-[[(1s,3s,5s)-2-[5-(3,4-difluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=C(F)C(F)=C1 RZISYTTYCMGRIV-XFQAVAEZSA-N 0.000 claims description 2
- AZDXLOMUOCNXEW-FGSXEWAUSA-N n-[[(1s,3s,5s)-2-[5-(3,4-difluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=NC=CC=C3C=CC=2)=C1C1=CC=C(F)C(F)=C1 AZDXLOMUOCNXEW-FGSXEWAUSA-N 0.000 claims description 2
- GUKRKVDEZFQTSH-QTEQDKRBSA-N n-[[(1s,3s,5s)-2-[5-(3,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=C(C)C(C)=C1 GUKRKVDEZFQTSH-QTEQDKRBSA-N 0.000 claims description 2
- KZQZKNMOTAMKQF-HKBOAZHASA-N n-[[(1s,3s,5s)-2-[5-(3,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2N3C=CC=CC3=NC=2)=C1C1=CC=C(C)C(C)=C1 KZQZKNMOTAMKQF-HKBOAZHASA-N 0.000 claims description 2
- QCPQDWCUHPQQOM-GPXNEJASSA-N n-[[(1s,3s,5s)-2-[5-(3,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=NC=CC=C3C=CC=2)=C1C1=CC=C(C)C(C)=C1 QCPQDWCUHPQQOM-GPXNEJASSA-N 0.000 claims description 2
- YDFURXOYOVOKJD-SFLYRZDNSA-N n-[[(1s,3s,5s)-2-[5-(3,5-dimethylphenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]quinoline-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=NC=CC=C3C=CC=2)=C1C1=CC(C)=CC(C)=C1 YDFURXOYOVOKJD-SFLYRZDNSA-N 0.000 claims description 2
- FEPGFYIHJOPNSL-XFQAVAEZSA-N n-[[(1s,3s,5s)-2-[5-(3-bromo-4-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=C(F)C(Br)=C1 FEPGFYIHJOPNSL-XFQAVAEZSA-N 0.000 claims description 2
- JOHGJYPTRQGDGY-GJYPPUQNSA-N n-[[(1s,3s,5s)-2-[5-(3-bromo-4-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2N3C=CC=CC3=NC=2)=C1C1=CC=C(F)C(Br)=C1 JOHGJYPTRQGDGY-GJYPPUQNSA-N 0.000 claims description 2
- ZUEMLXNMUXNLOR-NEWSRXKRSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-ethoxy-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound S1C(OCC)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2N3C=CC=CC3=NC=2)=C1C1=CC=CC(Cl)=C1 ZUEMLXNMUXNLOR-NEWSRXKRSA-N 0.000 claims description 2
- XUHKGEPMDCAIRN-AYBZRNKSSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1,2-benzoxazole-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=CC=CC=C3ON=2)=C1C1=CC=CC(Cl)=C1 XUHKGEPMDCAIRN-AYBZRNKSSA-N 0.000 claims description 2
- KULMNBBOQJYNOV-RFWXGWTQSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1,2-dimethylindole-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=CC=CC=C3N(C)C=2C)=C1C1=CC=CC(Cl)=C1 KULMNBBOQJYNOV-RFWXGWTQSA-N 0.000 claims description 2
- MZVIWUMTFZWTSC-KPFFTGBYSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1-ethyl-3-methylpyrazole-4-carboxamide Chemical compound CC1=NN(CC)C=C1C(=O)NC[C@H]1N(C(=O)C2=C(SC(C)=N2)C=2C=C(Cl)C=CC=2)[C@H]2C[C@H]2C1 MZVIWUMTFZWTSC-KPFFTGBYSA-N 0.000 claims description 2
- DLOVGCVIGXHUNF-SYNHAJSKSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1h-indazole-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=CC=CC=C3NN=2)=C1C1=CC=CC(Cl)=C1 DLOVGCVIGXHUNF-SYNHAJSKSA-N 0.000 claims description 2
- YIXBQPFPRXJUDG-NRJQMVOHSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-1h-indole-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C3=CC=CC=C3NC=2)=C1C1=CC=CC(Cl)=C1 YIXBQPFPRXJUDG-NRJQMVOHSA-N 0.000 claims description 2
- ZHSWDDMSCPEKSE-KPFFTGBYSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OCCOC=3C=CC=2)=C1C1=CC=CC(Cl)=C1 ZHSWDDMSCPEKSE-KPFFTGBYSA-N 0.000 claims description 2
- PJJFOLAESAPRLI-MMOPVJDHSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydro-1-benzofuran-4-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3CCOC=3C=CC=2)=C1C1=CC=CC(Cl)=C1 PJJFOLAESAPRLI-MMOPVJDHSA-N 0.000 claims description 2
- ZWCAZXXGONPGFK-PVAVHDDUSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,3-dihydrothieno[3,4-b][1,4]dioxine-5-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C2=C3OCCOC3=CS2)=C1C1=CC=CC(Cl)=C1 ZWCAZXXGONPGFK-PVAVHDDUSA-N 0.000 claims description 2
- YPFFTZMAJGPYGI-NJAFHUGGSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2,5-dimethylpyrazole-3-carboxamide Chemical compound CN1N=C(C)C=C1C(=O)NC[C@H]1N(C(=O)C2=C(SC(C)=N2)C=2C=C(Cl)C=CC=2)[C@H]2C[C@H]2C1 YPFFTZMAJGPYGI-NJAFHUGGSA-N 0.000 claims description 2
- KBSSVCYUMROVTM-NEWSRXKRSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-2-ethyl-5-methylpyrazole-3-carboxamide Chemical compound CCN1N=C(C)C=C1C(=O)NC[C@H]1N(C(=O)C2=C(SC(C)=N2)C=2C=C(Cl)C=CC=2)[C@H]2C[C@H]2C1 KBSSVCYUMROVTM-NEWSRXKRSA-N 0.000 claims description 2
- WWIBMKSHGULDKS-UXPWSPDFSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3-(trifluoromethyl)benzamide Chemical compound C([C@@H]1C[C@@H]2C[C@@H]2N1C(=O)C=1N=C(SC=1C=1C=C(Cl)C=CC=1)C)NC(=O)C1=CC=CC(C(F)(F)F)=C1 WWIBMKSHGULDKS-UXPWSPDFSA-N 0.000 claims description 2
- CCEVMRIFKIBBST-LMNJBCLMSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC=CC(C(=O)NC[C@H]2N([C@H]3C[C@H]3C2)C(=O)C2=C(SC(C)=N2)C=2C=C(Cl)C=CC=2)=C1 CCEVMRIFKIBBST-LMNJBCLMSA-N 0.000 claims description 2
- WVEYOGBDDMVQGW-NJAFHUGGSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-3-methylimidazo[2,1-b][1,3]thiazole-2-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C2=C(N3C=CN=C3S2)C)=C1C1=CC=CC(Cl)=C1 WVEYOGBDDMVQGW-NJAFHUGGSA-N 0.000 claims description 2
- AQHMWVQEGIXGRB-AGHHOFFYSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-5-fluoro-1-methylindole-2-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2N(C3=CC=C(F)C=C3C=2)C)=C1C1=CC=CC(Cl)=C1 AQHMWVQEGIXGRB-AGHHOFFYSA-N 0.000 claims description 2
- ABAFUSICQAJYHX-JJXUHFIVSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]-6-fluoro-4h-1,3-benzodioxine-8-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2C=3OCOCC=3C=C(F)C=2)=C1C1=CC=CC(Cl)=C1 ABAFUSICQAJYHX-JJXUHFIVSA-N 0.000 claims description 2
- AMRUTJGNGLZLAU-NEWSRXKRSA-N n-[[(1s,3s,5s)-2-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-2-azabicyclo[3.1.0]hexan-3-yl]methyl]imidazo[1,2-a]pyridine-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@@H](C[C@@H]3C[C@@H]32)CNC(=O)C=2N3C=CC=CC3=NC=2)=C1C1=CC=CC(Cl)=C1 AMRUTJGNGLZLAU-NEWSRXKRSA-N 0.000 claims description 2
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- PIURXAHSTOGOSU-UHFFFAOYSA-N ethyl imidazo[2,1-b][1,3]thiazole-6-carboxylate Chemical class C1=CSC2=NC(C(=O)OCC)=CN21 PIURXAHSTOGOSU-UHFFFAOYSA-N 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
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- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
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- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 125000004245 indazol-3-yl group Chemical group [H]N1N=C(*)C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000004254 isoquinolin-1-yl group Chemical group [H]C1=C([H])C2=C([H])C([H])=C([H])C([H])=C2C(*)=N1 0.000 description 1
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- 150000003951 lactams Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- OVWYEQOVUDKZNU-UHFFFAOYSA-N m-tolualdehyde Chemical compound CC1=CC=CC(C=O)=C1 OVWYEQOVUDKZNU-UHFFFAOYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
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- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- ZLZDIOLXIRKDMS-UHFFFAOYSA-N methanesulfonyl chloride methyl 5-[3-(methanesulfonamido)phenyl]-2-methyl-1,3-thiazole-4-carboxylate Chemical compound CS(=O)(=O)Cl.COC(=O)C=1N=C(SC1C1=CC(=CC=C1)NS(=O)(=O)C)C ZLZDIOLXIRKDMS-UHFFFAOYSA-N 0.000 description 1
- SVEZOHPWBLWBNO-UHFFFAOYSA-N methyl 1,3-benzothiazole-7-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1SC=N2 SVEZOHPWBLWBNO-UHFFFAOYSA-N 0.000 description 1
- TYUGYIMCRDPMPJ-UHFFFAOYSA-N methyl 2-amino-4-methyl-1,3-thiazole-5-carboxylate Chemical compound COC(=O)C=1SC(N)=NC=1C TYUGYIMCRDPMPJ-UHFFFAOYSA-N 0.000 description 1
- BHNURCLYJAQCOH-UHFFFAOYSA-N methyl 2-amino-5-(2-fluorophenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(N)SC(C=2C(=CC=CC=2)F)=C1C(=O)OC BHNURCLYJAQCOH-UHFFFAOYSA-N 0.000 description 1
- OQEQWDUKFQICQE-UHFFFAOYSA-N methyl 2-amino-5-(3-methoxyphenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(N)SC(C=2C=C(OC)C=CC=2)=C1C(=O)OC OQEQWDUKFQICQE-UHFFFAOYSA-N 0.000 description 1
- QTTYJRKPJUWDJF-UHFFFAOYSA-N methyl 2-amino-5-(4-fluorophenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(N)SC(C=2C=CC(F)=CC=2)=C1C(=O)OC QTTYJRKPJUWDJF-UHFFFAOYSA-N 0.000 description 1
- IFNKCMBUNJNHBP-UHFFFAOYSA-N methyl 2-amino-5-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylate Chemical compound N1=C(N)SC(C=2C=C(C=CC=2)C(F)(F)F)=C1C(=O)OC IFNKCMBUNJNHBP-UHFFFAOYSA-N 0.000 description 1
- TYCWJCTWFOCHEU-UHFFFAOYSA-N methyl 2-bromo-5-(3-fluorophenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(Br)SC(C=2C=C(F)C=CC=2)=C1C(=O)OC TYCWJCTWFOCHEU-UHFFFAOYSA-N 0.000 description 1
- UHCWHVMDQRKHGH-UHFFFAOYSA-N methyl 2-cyclopropyl-5-(2-fluorophenyl)-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C=1N=C(C2CC2)SC=1C1=CC=CC=C1F UHCWHVMDQRKHGH-UHFFFAOYSA-N 0.000 description 1
- IRHJCXQOKSJQHA-UHFFFAOYSA-N methyl 2-cyclopropyl-5-(3-fluoro-4-methylphenyl)-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C=1N=C(C2CC2)SC=1C1=CC=C(C)C(F)=C1 IRHJCXQOKSJQHA-UHFFFAOYSA-N 0.000 description 1
- QXDOBOMRMWVERX-UHFFFAOYSA-N methyl 2-cyclopropyl-5-(3-fluorophenyl)-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C=1N=C(C2CC2)SC=1C1=CC=CC(F)=C1 QXDOBOMRMWVERX-UHFFFAOYSA-N 0.000 description 1
- WWDKPPVDASUYOI-UHFFFAOYSA-N methyl 2-cyclopropyl-5-(4-fluorophenyl)-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C=1N=C(C2CC2)SC=1C1=CC=C(F)C=C1 WWDKPPVDASUYOI-UHFFFAOYSA-N 0.000 description 1
- SCUFYJALVFXFKM-UHFFFAOYSA-N methyl 2-cyclopropyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C=1N=C(C2CC2)SC=1C1=CC=CC(C(F)(F)F)=C1 SCUFYJALVFXFKM-UHFFFAOYSA-N 0.000 description 1
- AHBMPSQXPJICGL-UHFFFAOYSA-N methyl 2-methyl-5-[2-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C(=CC=CC=2)C(F)(F)F)=C1C(=O)OC AHBMPSQXPJICGL-UHFFFAOYSA-N 0.000 description 1
- XHEHMQNIGVXSSJ-UHFFFAOYSA-N methyl 2-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(C=CC=2)C(F)(F)F)=C1C(=O)OC XHEHMQNIGVXSSJ-UHFFFAOYSA-N 0.000 description 1
- GJRZVUXHSOWMTR-UHFFFAOYSA-N methyl 2H-1,4-benzoxazine-8-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1OCC=N2 GJRZVUXHSOWMTR-UHFFFAOYSA-N 0.000 description 1
- CWLJGXDLLCZZQZ-UHFFFAOYSA-N methyl 3-(3-bromo-4-fluorophenyl)-3-chloro-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(F)C(Br)=C1 CWLJGXDLLCZZQZ-UHFFFAOYSA-N 0.000 description 1
- UARSGBLPDNBQBR-UHFFFAOYSA-N methyl 3-chloro-2-oxo-3-[2-(trifluoromethyl)phenyl]propanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC=C1C(F)(F)F UARSGBLPDNBQBR-UHFFFAOYSA-N 0.000 description 1
- WMRURPZIMIFESM-UHFFFAOYSA-N methyl 3-chloro-3-(2-chloro-6-fluorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=C(F)C=CC=C1Cl WMRURPZIMIFESM-UHFFFAOYSA-N 0.000 description 1
- RWQXMFKYDFWJOF-UHFFFAOYSA-N methyl 3-chloro-3-(2-fluorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC=C1F RWQXMFKYDFWJOF-UHFFFAOYSA-N 0.000 description 1
- XXFGUFDHHNGPOQ-UHFFFAOYSA-N methyl 3-chloro-3-(3-fluoro-2-methylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC(F)=C1C XXFGUFDHHNGPOQ-UHFFFAOYSA-N 0.000 description 1
- GUOODCPHIJPXSD-UHFFFAOYSA-N methyl 3-chloro-3-(3-fluoro-4-methylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(C)C(F)=C1 GUOODCPHIJPXSD-UHFFFAOYSA-N 0.000 description 1
- CQJMTOZIDLSULV-UHFFFAOYSA-N methyl 3-chloro-3-(3-methoxyphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC(OC)=C1 CQJMTOZIDLSULV-UHFFFAOYSA-N 0.000 description 1
- QFZGJNRSDDUIIV-UHFFFAOYSA-N methyl 3-chloro-3-(3-nitrophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC([N+]([O-])=O)=C1 QFZGJNRSDDUIIV-UHFFFAOYSA-N 0.000 description 1
- MBNOEXGGOGKJNK-UHFFFAOYSA-N methyl 3-chloro-3-[3-fluoro-5-(trifluoromethyl)phenyl]-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC(F)=CC(C(F)(F)F)=C1 MBNOEXGGOGKJNK-UHFFFAOYSA-N 0.000 description 1
- GICYBPVXQLNXKH-UHFFFAOYSA-N methyl 3-oxo-4h-1,4-benzoxazine-5-carboxylate Chemical compound O1CC(=O)NC2=C1C=CC=C2C(=O)OC GICYBPVXQLNXKH-UHFFFAOYSA-N 0.000 description 1
- NIWLJRLGYZNNLM-UHFFFAOYSA-N methyl 3-oxo-4h-1,4-benzoxazine-8-carboxylate Chemical compound N1C(=O)COC2=C1C=CC=C2C(=O)OC NIWLJRLGYZNNLM-UHFFFAOYSA-N 0.000 description 1
- CSDLSCJJZZCOGL-UHFFFAOYSA-N methyl 4-methyl-2,3-dihydro-1,4-benzoxazine-8-carboxylate Chemical compound CN1CCOC2=C1C=CC=C2C(=O)OC CSDLSCJJZZCOGL-UHFFFAOYSA-N 0.000 description 1
- GILBTDVSPJAUDI-UHFFFAOYSA-N methyl 5-(2-fluorophenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(C=2C(=CC=CC=2)F)=C1C(=O)OC GILBTDVSPJAUDI-UHFFFAOYSA-N 0.000 description 1
- QDYMCURTXYHMOS-UHFFFAOYSA-N methyl 5-(3-aminophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(N)C=CC=2)=C1C(=O)OC QDYMCURTXYHMOS-UHFFFAOYSA-N 0.000 description 1
- DCDLZQJGQQFERM-UHFFFAOYSA-N methyl 5-(3-chlorophenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(C=2C=C(Cl)C=CC=2)=C1C(=O)OC DCDLZQJGQQFERM-UHFFFAOYSA-N 0.000 description 1
- GYBAYCMOZIBEDF-UHFFFAOYSA-N methyl 5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(Cl)C=CC=2)=C1C(=O)OC GYBAYCMOZIBEDF-UHFFFAOYSA-N 0.000 description 1
- OKOFEGOEEOZLSK-UHFFFAOYSA-N methyl 5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(F)C=CC=2)=C1C(=O)OC OKOFEGOEEOZLSK-UHFFFAOYSA-N 0.000 description 1
- YPMUOZNQKCAQJC-UHFFFAOYSA-N methyl 5-(3-methoxyphenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(C=2C=C(OC)C=CC=2)=C1C(=O)OC YPMUOZNQKCAQJC-UHFFFAOYSA-N 0.000 description 1
- KKTDZGNAPDYLEC-UHFFFAOYSA-N methyl 5-(3-methylphenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(C=2C=C(C)C=CC=2)=C1C(=O)OC KKTDZGNAPDYLEC-UHFFFAOYSA-N 0.000 description 1
- UIIASGDNJSVHCX-UHFFFAOYSA-N methyl 5-(4-bromophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=CC(Br)=CC=2)=C1C(=O)OC UIIASGDNJSVHCX-UHFFFAOYSA-N 0.000 description 1
- JYGKTWUGNIYBKS-UHFFFAOYSA-N methyl 5-(4-fluorophenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(C=2C=CC(F)=CC=2)=C1C(=O)OC JYGKTWUGNIYBKS-UHFFFAOYSA-N 0.000 description 1
- MILNSAORCXGXKI-UHFFFAOYSA-N methyl 5-(4-fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=CC(F)=CC=2)=C1C(=O)OC MILNSAORCXGXKI-UHFFFAOYSA-N 0.000 description 1
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- 125000002098 pyridazinyl group Chemical group 0.000 description 1
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- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000012201 sexual and gender identity disease Diseases 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
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- 229960005322 streptomycin Drugs 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
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- PCUVUHWTECINHT-BZSDZJHCSA-N tert-butyl (1S,3S,5S)-3-[(benzylamino)methyl]-2-azabicyclo[3.1.0]hexane-2-carboxylate phenylmethanamine Chemical compound C(C1=CC=CC=C1)N.C(C)(C)(C)OC(=O)N1[C@H]2C[C@H]2C[C@H]1CNCC1=CC=CC=C1 PCUVUHWTECINHT-BZSDZJHCSA-N 0.000 description 1
- DBOGUJDUACLSTB-VGMNWLOBSA-N tert-butyl (1s,3s,5s)-3-(hydroxymethyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate Chemical compound C1[C@@H](CO)N(C(=O)OC(C)(C)C)[C@H]2C[C@H]21 DBOGUJDUACLSTB-VGMNWLOBSA-N 0.000 description 1
- IPKQFAUFTBIMCK-IPYPFGDCSA-N tert-butyl (1s,3s,5s)-3-[(2,3-dihydro-1,4-benzodioxine-5-carbonylamino)methyl]-2-azabicyclo[3.1.0]hexane-2-carboxylate Chemical compound O1CCOC2=C1C=CC=C2C(=O)NC[C@@H]1C[C@@H]2C[C@@H]2N1C(=O)OC(C)(C)C IPKQFAUFTBIMCK-IPYPFGDCSA-N 0.000 description 1
- XAQMRBFMFFXEHT-WOPDTQHZSA-N tert-butyl (1s,3s,5s)-3-[(2,3-dihydrothieno[3,4-b][1,4]dioxine-5-carbonylamino)methyl]-2-azabicyclo[3.1.0]hexane-2-carboxylate Chemical compound S1C=C2OCCOC2=C1C(=O)NC[C@@H]1C[C@@H]2C[C@@H]2N1C(=O)OC(C)(C)C XAQMRBFMFFXEHT-WOPDTQHZSA-N 0.000 description 1
- DJYUDBBOZJFIHH-RDBSUJKOSA-N tert-butyl (1s,3s,5s)-3-[(imidazo[1,2-a]pyridine-3-carbonylamino)methyl]-2-azabicyclo[3.1.0]hexane-2-carboxylate Chemical compound C1=CC=CN2C(C(=O)NC[C@@H]3C[C@@H]4C[C@@H]4N3C(=O)OC(C)(C)C)=CN=C21 DJYUDBBOZJFIHH-RDBSUJKOSA-N 0.000 description 1
- KQWFECFQTWBGHN-AGIUHOORSA-N tert-butyl (1s,3s,5s)-3-[[(3,5-dimethyl-1,2-oxazole-4-carbonyl)amino]methyl]-2-azabicyclo[3.1.0]hexane-2-carboxylate Chemical compound CC1=NOC(C)=C1C(=O)NC[C@H]1N(C(=O)OC(C)(C)C)[C@H]2C[C@H]2C1 KQWFECFQTWBGHN-AGIUHOORSA-N 0.000 description 1
- GAJQYRGVSYRTJO-SNPRPXQTSA-N tert-butyl (1s,3s,5s)-3-[[(3-bromobenzoyl)amino]methyl]-2-azabicyclo[3.1.0]hexane-2-carboxylate Chemical compound C([C@@H]1C[C@@H]2C[C@@H]2N1C(=O)OC(C)(C)C)NC(=O)C1=CC=CC(Br)=C1 GAJQYRGVSYRTJO-SNPRPXQTSA-N 0.000 description 1
- SMDRERSSXIKZGF-USWWRNFRSA-N tert-butyl (1s,3s,5s)-3-[[(5-bromopyrimidin-2-yl)amino]methyl]-2-azabicyclo[3.1.0]hexane-2-carboxylate Chemical compound C([C@@H]1C[C@@H]2C[C@@H]2N1C(=O)OC(C)(C)C)NC1=NC=C(Br)C=N1 SMDRERSSXIKZGF-USWWRNFRSA-N 0.000 description 1
- MUIWYHBTQWVQKB-AGIUHOORSA-N tert-butyl (1s,3s,5s)-3-[[(6-methylimidazo[2,1-b][1,3]thiazole-5-carbonyl)amino]methyl]-2-azabicyclo[3.1.0]hexane-2-carboxylate Chemical compound C1[C@@H]2C[C@@H]2N(C(=O)OC(C)(C)C)[C@@H]1CNC(=O)C1=C(C)N=C2N1C=CS2 MUIWYHBTQWVQKB-AGIUHOORSA-N 0.000 description 1
- ZBNRVIGHEROTFW-UHFFFAOYSA-N tert-butyl 3-(aminomethyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate Chemical compound C1C(CN)N(C(=O)OC(C)(C)C)C2CC21 ZBNRVIGHEROTFW-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
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- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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Classifications
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Applications Claiming Priority (2)
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| PCT/IB2007/055326 WO2008081399A2 (en) | 2006-12-28 | 2007-12-28 | 2-aza-bicyclo[3.1.0]hexane derivatives as orexin receptor antagonists |
Publications (2)
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| JP2010514751A true JP2010514751A (ja) | 2010-05-06 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003051368A1 (en) * | 2001-12-19 | 2003-06-26 | Smithkline Beecham Plc | N-aroyl cyclic amine derivatives as orexin receptor antagonists |
| JP2004503537A (ja) * | 2000-06-16 | 2004-02-05 | スミスクライン ビーチャム パブリック リミテッド カンパニー | オレキシン受容体アンタゴニストとして使用するためのピペリジン |
| WO2004041791A1 (en) * | 2002-11-06 | 2004-05-21 | Glaxo Group Limited | N-aryl acetyl cyclic amine derivatives as orexin antagonists |
| WO2004041816A1 (en) * | 2002-11-06 | 2004-05-21 | Glaxo Group Limited | Azacyclic compounds as orexin receptor antagonist |
| WO2004085403A1 (en) * | 2003-03-26 | 2004-10-07 | Actelion Pharmaceuticals Ltd | Tetrahydroisoquinolyl acetamide derivatives for use as orexin receptor antagonists |
| JP2004533440A (ja) * | 2001-05-05 | 2004-11-04 | スミスクライン ビーチャム パブリック リミテッド カンパニー | N−アロイルサイクリックアミン |
| JP2004534026A (ja) * | 2001-05-05 | 2004-11-11 | スミスクライン ビーチャム パブリック リミテッド カンパニー | オレキシン受容体アンタゴニストとしてのn−アロイルサイクリックアミン誘導体 |
| WO2004096780A1 (en) * | 2003-04-28 | 2004-11-11 | Actelion Pharmaceuticals Ltd | Quinoxalinone-3- one derivatives as orexin receptor antagonists |
| JP2005501027A (ja) * | 2001-06-28 | 2005-01-13 | スミスクライン ビーチャム パブリック リミテッド カンパニー | オレキシン受容体アンタゴニストとしてのn−アロイル環状アミン誘導体 |
| JP2005501026A (ja) * | 2001-06-28 | 2005-01-13 | スミスクライン ビーチャム パブリック リミテッド カンパニー | 化合物 |
| JP2005505603A (ja) * | 2001-10-11 | 2005-02-24 | スミスクライン ビーチャム パブリック リミテッド カンパニー | オレキシン受容体アンタゴニストとしてのn−アロイルピペラジン誘導体 |
| JP2005513011A (ja) * | 2001-11-10 | 2005-05-12 | スミスクライン ビーチャム パブリック リミテッド カンパニー | ピペラジンビス−アミド誘導体およびオレキシン受容体のアンタゴニストとしてのその使用 |
| WO2005118548A1 (en) * | 2004-03-01 | 2005-12-15 | Actelion Pharmaceuticals Ltd | Substituted 1,2,3,4-tetrahydroisoquinoline derivatives |
| JP2006504695A (ja) * | 2002-09-18 | 2006-02-09 | グラクソ グループ リミテッド | オレキシン受容体アンタゴニストとしてのn−アロイル環状アミン |
| JP2010504957A (ja) * | 2006-09-29 | 2010-02-18 | アクテリオン ファーマシューティカルズ リミテッド | 3−アザ−ビシクロ[3.1.0]ヘキサン誘導体 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH621126A5 (enExample) | 1974-02-07 | 1981-01-15 | Plantex Ltd | |
| WO1995029922A1 (en) | 1994-04-29 | 1995-11-09 | Pharmacia & Upjohn Company | Methanol derivatives for treatment of retroviral infections especially hiv infections |
| JP2004533989A (ja) | 2000-11-20 | 2004-11-11 | サイオス インコーポレイテッド | p38キナーゼのピペリジン/ピペラジン型阻害剤 |
| WO2002044172A1 (en) | 2000-11-28 | 2002-06-06 | Smithkline Beecham P.L.C. | Morpholine derivatives as antagonists of orexin receptors |
| GB0111341D0 (en) | 2001-05-10 | 2001-07-04 | Bp Chem Int Ltd | Novel polymerisation catalysts |
| US6727247B2 (en) * | 2001-12-10 | 2004-04-27 | Hoffman-La Roche Inc. | Substituted benzothiazole amide derivatives |
| GB0130393D0 (en) * | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| US6995144B2 (en) | 2002-03-14 | 2006-02-07 | Eisai Co., Ltd. | Nitrogen containing heterocyclic compounds and medicines containing the same |
| GB0225938D0 (en) | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| US20060014733A1 (en) | 2004-07-19 | 2006-01-19 | Pfizer Inc | Histamine-3 agonists and antagonists |
| PL2069332T3 (pl) | 2006-08-15 | 2011-07-29 | Actelion Pharmaceuticals Ltd | Związki azetydynowe jako antagoniści receptorów oreksynowych |
| WO2008065626A2 (en) | 2006-12-01 | 2008-06-05 | Actelion Pharmaceuticals Ltd | 3-heteroaryl (amino or amido)-1- (biphenyl or phenylthiazolyl) carbonylpiperidine derivativesas orexin receptor inhibitors |
| CL2008000836A1 (es) | 2007-03-26 | 2008-11-07 | Actelion Pharmaceuticals Ltd | Compuestos derivados de tiazolidina, antagonistas del receptor de orexina; composicion farmaceutica que los comprende; y su uso en el tratamiento de neurosis emocional, depresion grave, trastornos psicoticos, alzheimer, parkinson, dolor, entre otras. |
| US20100222328A1 (en) | 2007-05-14 | 2010-09-02 | Hamed Aissaoui | 2-cyclopropyl-thiazole derivatives |
| HRP20120240T1 (hr) | 2007-05-23 | 2012-04-30 | Merck Sharp & Dohme Corp. | Piridil piperidin antagonisti receptora za oreksin |
| US8030495B2 (en) | 2007-05-23 | 2011-10-04 | Coleman Paul J | Cyclopropyl pyrrolidine orexin receptor antagonists |
| CA2691373A1 (en) | 2007-07-03 | 2009-01-08 | Actelion Pharmaceuticals Ltd | 3-aza-bicyclo[3.3.0]octane compounds |
| AR067665A1 (es) | 2007-07-27 | 2009-10-21 | Actelion Pharmaceuticals Ltd | Derivados de trans-3- aza-biciclo ( 3.1.0) hexano |
| NZ583487A (en) | 2007-07-27 | 2011-09-30 | Actelion Pharmaceuticals Ltd | 2-aza-bicyclo[3.3.0]octane derivatives |
| EP2207778A2 (en) | 2007-09-24 | 2010-07-21 | Actelion Pharmaceuticals Ltd. | Pyrrolidines and piperidines as orexin receptor antagonists |
| NZ588080A (en) | 2008-02-21 | 2012-04-27 | Actelion Pharmaceuticals Ltd | 2-Aza-bicyclo[2.2.1]heptane derivatives |
| CA2722347A1 (en) | 2008-04-30 | 2009-11-05 | Actelion Pharmaceuticals Ltd | Piperidine and pyrrolidine compounds |
| TW200940822A (en) * | 2009-05-07 | 2009-10-01 | Wan Chi Steel Ind Co Ltd | Water wheel mechanism with sun-and-planet type blade |
-
2007
- 2007-12-27 CL CL200703827A patent/CL2007003827A1/es unknown
- 2007-12-27 AR ARP070105930A patent/AR064561A1/es not_active Application Discontinuation
- 2007-12-27 TW TW096150631A patent/TW200833328A/zh unknown
- 2007-12-28 BR BRPI0720876-6A patent/BRPI0720876A2/pt not_active IP Right Cessation
- 2007-12-28 RU RU2009128739/04A patent/RU2460732C2/ru not_active IP Right Cessation
- 2007-12-28 JP JP2009543566A patent/JP2010514751A/ja active Pending
- 2007-12-28 ES ES07859531T patent/ES2364297T3/es active Active
- 2007-12-28 DE DE602007013937T patent/DE602007013937D1/de active Active
- 2007-12-28 HR HR20110509T patent/HRP20110509T1/hr unknown
- 2007-12-28 DK DK07859531.1T patent/DK2094690T3/da active
- 2007-12-28 MX MX2009006860A patent/MX2009006860A/es active IP Right Grant
- 2007-12-28 AU AU2007340944A patent/AU2007340944B2/en not_active Expired - Fee Related
- 2007-12-28 AT AT07859531T patent/ATE505467T1/de active
- 2007-12-28 CN CN2007800483236A patent/CN101568536B/zh not_active Expired - Fee Related
- 2007-12-28 EP EP07859531A patent/EP2094690B1/en active Active
- 2007-12-28 NZ NZ578642A patent/NZ578642A/en not_active IP Right Cessation
- 2007-12-28 CA CA002669821A patent/CA2669821A1/en not_active Abandoned
- 2007-12-28 PT PT07859531T patent/PT2094690E/pt unknown
- 2007-12-28 PL PL07859531T patent/PL2094690T3/pl unknown
- 2007-12-28 WO PCT/IB2007/055326 patent/WO2008081399A2/en not_active Ceased
- 2007-12-28 US US12/521,453 patent/US8288435B2/en not_active Expired - Fee Related
- 2007-12-28 SI SI200730639T patent/SI2094690T1/sl unknown
- 2007-12-28 MY MYPI20092751A patent/MY157344A/en unknown
- 2007-12-28 KR KR1020097015732A patent/KR20090094168A/ko not_active Ceased
-
2009
- 2009-06-17 MA MA32004A patent/MA31000B1/fr unknown
- 2009-07-27 NO NO20092762A patent/NO20092762L/no not_active Application Discontinuation
- 2009-07-27 ZA ZA200905229A patent/ZA200905229B/xx unknown
-
2011
- 2011-07-13 CY CY20111100681T patent/CY1111705T1/el unknown
Patent Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004503537A (ja) * | 2000-06-16 | 2004-02-05 | スミスクライン ビーチャム パブリック リミテッド カンパニー | オレキシン受容体アンタゴニストとして使用するためのピペリジン |
| JP2004533440A (ja) * | 2001-05-05 | 2004-11-04 | スミスクライン ビーチャム パブリック リミテッド カンパニー | N−アロイルサイクリックアミン |
| JP2004534026A (ja) * | 2001-05-05 | 2004-11-11 | スミスクライン ビーチャム パブリック リミテッド カンパニー | オレキシン受容体アンタゴニストとしてのn−アロイルサイクリックアミン誘導体 |
| JP2005501026A (ja) * | 2001-06-28 | 2005-01-13 | スミスクライン ビーチャム パブリック リミテッド カンパニー | 化合物 |
| JP2005501027A (ja) * | 2001-06-28 | 2005-01-13 | スミスクライン ビーチャム パブリック リミテッド カンパニー | オレキシン受容体アンタゴニストとしてのn−アロイル環状アミン誘導体 |
| JP2005505603A (ja) * | 2001-10-11 | 2005-02-24 | スミスクライン ビーチャム パブリック リミテッド カンパニー | オレキシン受容体アンタゴニストとしてのn−アロイルピペラジン誘導体 |
| JP2005513011A (ja) * | 2001-11-10 | 2005-05-12 | スミスクライン ビーチャム パブリック リミテッド カンパニー | ピペラジンビス−アミド誘導体およびオレキシン受容体のアンタゴニストとしてのその使用 |
| WO2003051368A1 (en) * | 2001-12-19 | 2003-06-26 | Smithkline Beecham Plc | N-aroyl cyclic amine derivatives as orexin receptor antagonists |
| JP2006504695A (ja) * | 2002-09-18 | 2006-02-09 | グラクソ グループ リミテッド | オレキシン受容体アンタゴニストとしてのn−アロイル環状アミン |
| WO2004041816A1 (en) * | 2002-11-06 | 2004-05-21 | Glaxo Group Limited | Azacyclic compounds as orexin receptor antagonist |
| WO2004041791A1 (en) * | 2002-11-06 | 2004-05-21 | Glaxo Group Limited | N-aryl acetyl cyclic amine derivatives as orexin antagonists |
| WO2004085403A1 (en) * | 2003-03-26 | 2004-10-07 | Actelion Pharmaceuticals Ltd | Tetrahydroisoquinolyl acetamide derivatives for use as orexin receptor antagonists |
| WO2004096780A1 (en) * | 2003-04-28 | 2004-11-11 | Actelion Pharmaceuticals Ltd | Quinoxalinone-3- one derivatives as orexin receptor antagonists |
| WO2005118548A1 (en) * | 2004-03-01 | 2005-12-15 | Actelion Pharmaceuticals Ltd | Substituted 1,2,3,4-tetrahydroisoquinoline derivatives |
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