RU2478099C2 - Производные 2-аза-бицикло[3.3.0]октана - Google Patents
Производные 2-аза-бицикло[3.3.0]октана Download PDFInfo
- Publication number
- RU2478099C2 RU2478099C2 RU2010106854/04A RU2010106854A RU2478099C2 RU 2478099 C2 RU2478099 C2 RU 2478099C2 RU 2010106854/04 A RU2010106854/04 A RU 2010106854/04A RU 2010106854 A RU2010106854 A RU 2010106854A RU 2478099 C2 RU2478099 C2 RU 2478099C2
- Authority
- RU
- Russia
- Prior art keywords
- carboxylic acid
- azabicyclo
- amide
- carbonyl
- octan
- Prior art date
Links
- ADKDJHASTPQGEO-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydrocyclopenta[b]pyrrole Chemical class C1CNC2CCCC21 ADKDJHASTPQGEO-UHFFFAOYSA-N 0.000 title abstract description 10
- -1 benzoisoxazolyl group Chemical group 0.000 claims abstract description 54
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 27
- 150000002367 halogens Chemical class 0.000 claims abstract description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 21
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 7
- 230000000694 effects Effects 0.000 claims abstract description 5
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims abstract description 3
- 229940123730 Orexin receptor antagonist Drugs 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims description 54
- 125000001424 substituent group Chemical group 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 208000019116 sleep disease Diseases 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 5
- 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 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
- LJZNNVINQVABLC-JBACZVJFSA-N C1(CC1)C=1SC(=C(N1)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1CC1=CC=CC2=C1C(=NO2)C(=O)N)C2=CC=CC=C2 Chemical compound C1(CC1)C=1SC(=C(N1)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1CC1=CC=CC2=C1C(=NO2)C(=O)N)C2=CC=CC=C2 LJZNNVINQVABLC-JBACZVJFSA-N 0.000 claims description 2
- NMECYMRCJJLFGF-VSZGBHKWSA-N C1(CC1)C=1SC(=C(N1)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1CC1OC=2C(C1)=C(C=CC2)C(=O)N)C2=CC=CC=C2 Chemical compound C1(CC1)C=1SC(=C(N1)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1CC1OC=2C(C1)=C(C=CC2)C(=O)N)C2=CC=CC=C2 NMECYMRCJJLFGF-VSZGBHKWSA-N 0.000 claims description 2
- KUDOSRQCELYFMT-NZZVAKLFSA-N CC(NC1=CC=CC(C2=C(C(N3[C@@H](CCC4)[C@@H]4C[C@H]3CN)=O)N=C(C)S2)=C1)=O.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC(NC1=CC=CC(C2=C(C(N3[C@@H](CCC4)[C@@H]4C[C@H]3CN)=O)N=C(C)S2)=C1)=O.OC(C1=C(CCO2)C2=CC=C1)=O KUDOSRQCELYFMT-NZZVAKLFSA-N 0.000 claims description 2
- FPTHOEVVNURUHO-WDTSGDEMSA-N CC1=C(C(O)=O)N(C=CS2)C2=N1.CC(C=C1)=CC=C1C1=C(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)N=C(N)S1 Chemical compound CC1=C(C(O)=O)N(C=CS2)C2=N1.CC(C=C1)=CC=C1C1=C(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)N=C(N)S1 FPTHOEVVNURUHO-WDTSGDEMSA-N 0.000 claims description 2
- IZPBIWIJPSUEDI-GEUPQXMHSA-N CC1=C(C(O)=O)N(C=CS2)C2=N1.CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC=C2F)S1 Chemical compound CC1=C(C(O)=O)N(C=CS2)C2=N1.CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC=C2F)S1 IZPBIWIJPSUEDI-GEUPQXMHSA-N 0.000 claims description 2
- YRCYTHUQODRVDF-VMESOOAKSA-N CC1=C(C(O)=O)N(C=CS2)C2=N1.CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC(Cl)=CC=C2)S1 Chemical compound CC1=C(C(O)=O)N(C=CS2)C2=N1.CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC(Cl)=CC=C2)S1 YRCYTHUQODRVDF-VMESOOAKSA-N 0.000 claims description 2
- VJPCPKIQEGUFLQ-VMESOOAKSA-N CC1=C(C(O)=O)N(C=CS2)C2=N1.CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC(F)=CC=C2)S1 Chemical compound CC1=C(C(O)=O)N(C=CS2)C2=N1.CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC(F)=CC=C2)S1 VJPCPKIQEGUFLQ-VMESOOAKSA-N 0.000 claims description 2
- VDMOQKPYOHHESN-FRKSIBALSA-N CC1=C(C(O)=O)N(C=CS2)C2=N1.CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC=C(C)C=C2)S1 Chemical compound CC1=C(C(O)=O)N(C=CS2)C2=N1.CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC=C(C)C=C2)S1 VDMOQKPYOHHESN-FRKSIBALSA-N 0.000 claims description 2
- UFOGIILZRFAIGV-BDURURIASA-N CC1=C(C(O)=O)N(C=CS2)C2=N1.NC[C@H](C[C@H]1[C@@H]2CCC1)N2C(C1=C(C(C=C2)=CC=C2F)SC(C2CC2)=N1)=O Chemical compound CC1=C(C(O)=O)N(C=CS2)C2=N1.NC[C@H](C[C@H]1[C@@H]2CCC1)N2C(C1=C(C(C=C2)=CC=C2F)SC(C2CC2)=N1)=O UFOGIILZRFAIGV-BDURURIASA-N 0.000 claims description 2
- QEELJUHJXXMQHM-OYAYLOLSSA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC(Br)=C2F)S1.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC(Br)=C2F)S1.OC(C1=C(CCO2)C2=CC=C1)=O QEELJUHJXXMQHM-OYAYLOLSSA-N 0.000 claims description 2
- VXVKYOIEJKCBLR-OYAYLOLSSA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC(F)=C2F)S1.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC(F)=C2F)S1.OC(C1=C(CCO2)C2=CC=C1)=O VXVKYOIEJKCBLR-OYAYLOLSSA-N 0.000 claims description 2
- ADBRSVWDGSREFQ-GEUPQXMHSA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC=C2Br)S1.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC=C2Br)S1.OC(C1=C(CCO2)C2=CC=C1)=O ADBRSVWDGSREFQ-GEUPQXMHSA-N 0.000 claims description 2
- KGUBPTMUQPIVMR-GEUPQXMHSA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC=C2F)S1.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC=C2F)S1.OC(C1=C(CCO2)C2=CC=C1)=O KGUBPTMUQPIVMR-GEUPQXMHSA-N 0.000 claims description 2
- AVHNMADSNBYYFL-OVHUVXHOSA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=C(C)C=C(C)C=C2)S1.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=C(C)C=C(C)C=C2)S1.OC(C1=C(CCO2)C2=CC=C1)=O AVHNMADSNBYYFL-OVHUVXHOSA-N 0.000 claims description 2
- MRXUYDNTYNUZKN-OOAIBONUSA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC(C)=C(C)C=C2)S1.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC(C)=C(C)C=C2)S1.OC(C1=C(CCO2)C2=CC=C1)=O MRXUYDNTYNUZKN-OOAIBONUSA-N 0.000 claims description 2
- AWJORMCYJLCRBA-OOAIBONUSA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC(C)=CC(C)=C2)S1.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC(C)=CC(C)=C2)S1.OC(C1=C(CCO2)C2=CC=C1)=O AWJORMCYJLCRBA-OOAIBONUSA-N 0.000 claims description 2
- IBLJREUPGFXOHE-VMESOOAKSA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC(F)=CC=C2)S1.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC(F)=CC=C2)S1.OC(C1=C(CCO2)C2=CC=C1)=O IBLJREUPGFXOHE-VMESOOAKSA-N 0.000 claims description 2
- PNBZGOFHXWCWMI-FRKSIBALSA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC=C(C)C=C2)S1.OC(C1=NOC2=C1C=CC=C2)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC=C(C)C=C2)S1.OC(C1=NOC2=C1C=CC=C2)=O PNBZGOFHXWCWMI-FRKSIBALSA-N 0.000 claims description 2
- BKJZFSFCDRJENR-BDURURIASA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC=CC(C)=C2)S1.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C2=CC=CC(C)=C2)S1.OC(C1=C(CCO2)C2=CC=C1)=O BKJZFSFCDRJENR-BDURURIASA-N 0.000 claims description 2
- GMRSKIRPJYVVMB-CWHRKKIYSA-N CC=1SC(=C(N1)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1CC1OC=2C(C1)=C(C=CC2)C(=O)N)C2=CC=CC=C2 Chemical compound CC=1SC(=C(N1)C(=O)N1[C@H]2CCC[C@H]2C[C@H]1CC1OC=2C(C1)=C(C=CC2)C(=O)N)C2=CC=CC=C2 GMRSKIRPJYVVMB-CWHRKKIYSA-N 0.000 claims description 2
- ULHOSVCLDWIENT-OOVPJUSVSA-N O1C(CC2=C1C=CC=C2)C(=O)NC[C@H]2N([C@H]1CCC[C@H]1C2)C(=O)C=2N=C(SC2C2=CC(=CC=C2)Cl)C Chemical compound O1C(CC2=C1C=CC=C2)C(=O)NC[C@H]2N([C@H]1CCC[C@H]1C2)C(=O)C=2N=C(SC2C2=CC(=CC=C2)Cl)C ULHOSVCLDWIENT-OOVPJUSVSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- DOTCHYMEKCDVKK-LRQRDZAKSA-N n-[[(2s,3as,6as)-1-[5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-1,2-benzoxazole-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C3=CC=CC=C3ON=2)=C1C1=CC=CC(Cl)=C1 DOTCHYMEKCDVKK-LRQRDZAKSA-N 0.000 claims description 2
- GBOFRAOTAREROM-LRQRDZAKSA-N n-[[(2s,3as,6as)-1-[5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carbonyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrol-2-yl]methyl]-1,2-benzoxazole-3-carboxamide Chemical compound S1C(C)=NC(C(=O)N2[C@H]3CCC[C@H]3C[C@H]2CNC(=O)C=2C3=CC=CC=C3ON=2)=C1C1=CC=CC(F)=C1 GBOFRAOTAREROM-LRQRDZAKSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 55
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 31
- 230000015572 biosynthetic process Effects 0.000 description 30
- 238000003786 synthesis reaction Methods 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 28
- 238000007127 saponification reaction Methods 0.000 description 27
- 125000003545 alkoxy group Chemical group 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 25
- 125000000623 heterocyclic group Chemical group 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000010410 layer Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 20
- 201000010099 disease Diseases 0.000 description 18
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 18
- HKMLRUAPIDAGIE-UHFFFAOYSA-N methyl 2,2-dichloroacetate Chemical compound COC(=O)C(Cl)Cl HKMLRUAPIDAGIE-UHFFFAOYSA-N 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 12
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 11
- 208000002193 Pain Diseases 0.000 description 11
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 11
- 238000007429 general method Methods 0.000 description 11
- 206010022437 insomnia Diseases 0.000 description 11
- 102000002512 Orexin Human genes 0.000 description 10
- 150000001299 aldehydes Chemical class 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 108060005714 orexin Proteins 0.000 description 10
- 230000036407 pain Effects 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 9
- 208000011580 syndromic disease Diseases 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 125000001309 chloro group Chemical group Cl* 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 208000020016 psychiatric disease Diseases 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 7
- RXNZFHIEDZEUQM-UHFFFAOYSA-N 2-bromo-1,3-thiazole Chemical class BrC1=NC=CS1 RXNZFHIEDZEUQM-UHFFFAOYSA-N 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 150000002148 esters Chemical group 0.000 description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 6
- 102000008834 Orexin receptor Human genes 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- 150000001732 carboxylic acid derivatives 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
- 238000004440 column chromatography Methods 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- FSTIEWRLYHVVHE-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole-2-carboxylic acid Chemical class C1=CN=C2SC(C(=O)O)=CN21 FSTIEWRLYHVVHE-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 208000012902 Nervous system disease Diseases 0.000 description 5
- 208000025966 Neurological disease Diseases 0.000 description 5
- 108050000742 Orexin Receptor Proteins 0.000 description 5
- 239000012317 TBTU Substances 0.000 description 5
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 208000010877 cognitive disease Diseases 0.000 description 5
- 239000012894 fetal calf serum Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- HMVYYTRDXNKRBQ-UHFFFAOYSA-N 1,3-thiazole-4-carboxylic acid Chemical class OC(=O)C1=CSC=N1 HMVYYTRDXNKRBQ-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- 239000012981 Hank's balanced salt solution Substances 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 4
- AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 description 4
- 230000004064 dysfunction Effects 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 150000002460 imidazoles Chemical class 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 201000003631 narcolepsy Diseases 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229940001470 psychoactive drug Drugs 0.000 description 4
- 239000004089 psychotropic agent Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- MJQHQXCRFBXKHR-DCAQKATOSA-N tert-butyl (2s,3as,6as)-2-(aminomethyl)-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrole-1-carboxylate Chemical compound C1CC[C@@H]2N(C(=O)OC(C)(C)C)[C@H](CN)C[C@@H]21 MJQHQXCRFBXKHR-DCAQKATOSA-N 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000008673 vomiting Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 206010012335 Dependence Diseases 0.000 description 3
- 208000012661 Dyskinesia Diseases 0.000 description 3
- 208000030814 Eating disease Diseases 0.000 description 3
- 208000019454 Feeding and Eating disease Diseases 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 208000005793 Restless legs syndrome Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 235000014632 disordered eating Nutrition 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- CPLITJZCMPATMH-UHFFFAOYSA-N methyl 2-cyclopropyl-1,3-thiazole-4-carboxylate Chemical class COC(=O)C1=CSC(C2CC2)=N1 CPLITJZCMPATMH-UHFFFAOYSA-N 0.000 description 3
- NQKNKJHAHDPQLC-UHFFFAOYSA-N methyl 3-chloro-2-oxo-3-[3-(trifluoromethyl)phenyl]propanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC(C(F)(F)F)=C1 NQKNKJHAHDPQLC-UHFFFAOYSA-N 0.000 description 3
- LQGLOOLNAIZIIW-UHFFFAOYSA-N methyl 3-chloro-2-oxo-3-phenylpropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC=C1 LQGLOOLNAIZIIW-UHFFFAOYSA-N 0.000 description 3
- CWKDZIZWTUMWRZ-UHFFFAOYSA-N methyl 3-chloro-3-(4-fluorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(F)C=C1 CWKDZIZWTUMWRZ-UHFFFAOYSA-N 0.000 description 3
- SJZWGZDVQIMLDL-UHFFFAOYSA-N methyl 3-chloro-3-(4-methylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(C)C=C1 SJZWGZDVQIMLDL-UHFFFAOYSA-N 0.000 description 3
- MEIOXBKJUCTLFN-UHFFFAOYSA-N methyl 5-(3-acetamidophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(NC(C)=O)C=CC=2)=C1C(=O)OC MEIOXBKJUCTLFN-UHFFFAOYSA-N 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- OFNHNCAUVYOTPM-IIIOAANCSA-N orexin-a Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@H](C(N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N2)[C@@H](C)O)=O)CSSC1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NC(=O)CC1)C1=CNC=N1 OFNHNCAUVYOTPM-IIIOAANCSA-N 0.000 description 3
- 125000002971 oxazolyl group Chemical group 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 208000022925 sleep disturbance Diseases 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 150000007979 thiazole derivatives Chemical class 0.000 description 3
- 150000003556 thioamides Chemical class 0.000 description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- DDGHBOLOCQWPKE-UHFFFAOYSA-N 1,3-thiazole;hydrobromide Chemical compound [Br-].C1=CSC=[NH+]1 DDGHBOLOCQWPKE-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- NMPVEAUIHMEAQP-UHFFFAOYSA-N 2-Bromoacetaldehyde Chemical compound BrCC=O NMPVEAUIHMEAQP-UHFFFAOYSA-N 0.000 description 2
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 2
- XTBMPXCBPYLZAL-UHFFFAOYSA-N 5-(3,5-dimethylphenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC(C)=CC(C)=C1 XTBMPXCBPYLZAL-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000000103 Anorexia Nervosa Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010006550 Bulimia nervosa Diseases 0.000 description 2
- FHJKNPJFTIYTMS-FXQIFTODSA-N C1CC[C@@H]2N[C@H](CN)C[C@@H]21 Chemical class C1CC[C@@H]2N[C@H](CN)C[C@@H]21 FHJKNPJFTIYTMS-FXQIFTODSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000028698 Cognitive impairment Diseases 0.000 description 2
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 2
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
- 208000014094 Dystonic disease Diseases 0.000 description 2
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 2
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical class NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 2
- 208000016988 Hemorrhagic Stroke Diseases 0.000 description 2
- 208000032382 Ischaemic stroke Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 206010033664 Panic attack Diseases 0.000 description 2
- 208000006199 Parasomnias Diseases 0.000 description 2
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 206010046543 Urinary incontinence Diseases 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229950003476 aminothiazole Drugs 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 235000021407 appetite control Nutrition 0.000 description 2
- 125000006267 biphenyl group Chemical group 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000005888 cyclopropanation reaction Methods 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 230000035622 drinking Effects 0.000 description 2
- 208000010118 dystonia Diseases 0.000 description 2
- 235000005686 eating Nutrition 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 208000037870 generalized anxiety Diseases 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- UFBBWLWUIISIPW-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole Chemical class C1=CSC2=NC=CN21 UFBBWLWUIISIPW-UHFFFAOYSA-N 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 230000013016 learning Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000006386 memory function Effects 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- JLOLKCQMMPWPIF-UHFFFAOYSA-N methyl 2-amino-5-(4-methylphenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(N)SC(C=2C=CC(C)=CC=2)=C1C(=O)OC JLOLKCQMMPWPIF-UHFFFAOYSA-N 0.000 description 2
- 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 2
- XQYYRAODNDHRMR-UHFFFAOYSA-N methyl 2-bromo-5-(4-fluorophenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(Br)SC(C=2C=CC(F)=CC=2)=C1C(=O)OC XQYYRAODNDHRMR-UHFFFAOYSA-N 0.000 description 2
- JHORCSVRNZPVES-UHFFFAOYSA-N methyl 2-bromo-5-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylate Chemical compound N1=C(Br)SC(C=2C=C(C=CC=2)C(F)(F)F)=C1C(=O)OC JHORCSVRNZPVES-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 2
- QADISPUHCVHWRY-UHFFFAOYSA-N methyl 2-cyclopropyl-5-phenyl-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C=1N=C(C2CC2)SC=1C1=CC=CC=C1 QADISPUHCVHWRY-UHFFFAOYSA-N 0.000 description 2
- NQIAJWCHXLSJNG-UHFFFAOYSA-N methyl 2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(C)C=CC=2)=C1C(=O)OC NQIAJWCHXLSJNG-UHFFFAOYSA-N 0.000 description 2
- GQHGXOLHISGWFR-UHFFFAOYSA-N methyl 2-methyl-5-(3-nitrophenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(C=CC=2)[N+]([O-])=O)=C1C(=O)OC GQHGXOLHISGWFR-UHFFFAOYSA-N 0.000 description 2
- WKUGTQAAIROIET-UHFFFAOYSA-N methyl 2-methyl-5-(4-methylphenyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=CC(C)=CC=2)=C1C(=O)OC WKUGTQAAIROIET-UHFFFAOYSA-N 0.000 description 2
- 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 2
- PWSNIVMZHJOKSE-UHFFFAOYSA-N methyl 2-methyl-5-phenyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=CC=CC=2)=C1C(=O)OC PWSNIVMZHJOKSE-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ZMPNWNKTWXYIPU-UHFFFAOYSA-N methyl 3-(4-bromophenyl)-3-chloro-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(Br)C=C1 ZMPNWNKTWXYIPU-UHFFFAOYSA-N 0.000 description 2
- WSDVMICATORZTN-UHFFFAOYSA-N methyl 3-chloro-3-(2,4-dimethylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(C)C=C1C WSDVMICATORZTN-UHFFFAOYSA-N 0.000 description 2
- ATDPEFWPMHGKGM-UHFFFAOYSA-N methyl 3-chloro-3-(3,4-dichlorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(Cl)C(Cl)=C1 ATDPEFWPMHGKGM-UHFFFAOYSA-N 0.000 description 2
- GCELVOMABNBSJG-UHFFFAOYSA-N methyl 3-chloro-3-(3,4-difluorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(F)C(F)=C1 GCELVOMABNBSJG-UHFFFAOYSA-N 0.000 description 2
- SRQLCRLPEMBIIH-UHFFFAOYSA-N methyl 3-chloro-3-(3,4-dimethylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=C(C)C(C)=C1 SRQLCRLPEMBIIH-UHFFFAOYSA-N 0.000 description 2
- IZOJNEZHOQKSKC-UHFFFAOYSA-N methyl 3-chloro-3-(3,5-dimethylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC(C)=CC(C)=C1 IZOJNEZHOQKSKC-UHFFFAOYSA-N 0.000 description 2
- QNFXEECTBCIMFP-UHFFFAOYSA-N methyl 3-chloro-3-(3-chlorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC(Cl)=C1 QNFXEECTBCIMFP-UHFFFAOYSA-N 0.000 description 2
- ZFDZEKPSKRJHJK-UHFFFAOYSA-N methyl 3-chloro-3-(3-fluorophenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC(F)=C1 ZFDZEKPSKRJHJK-UHFFFAOYSA-N 0.000 description 2
- DNTLNDGNTHOJIZ-UHFFFAOYSA-N methyl 3-chloro-3-(3-methylphenyl)-2-oxopropanoate Chemical compound COC(=O)C(=O)C(Cl)C1=CC=CC(C)=C1 DNTLNDGNTHOJIZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- KZOXLFIUUVATMN-UHFFFAOYSA-N methyl 5-(2,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C(=CC(C)=CC=2)C)=C1C(=O)OC KZOXLFIUUVATMN-UHFFFAOYSA-N 0.000 description 2
- YGTYCVKLOJHTEU-UHFFFAOYSA-N methyl 5-(3,4-dichlorophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(Cl)C(Cl)=CC=2)=C1C(=O)OC YGTYCVKLOJHTEU-UHFFFAOYSA-N 0.000 description 2
- XCXIVLCMRKWWQY-UHFFFAOYSA-N methyl 5-(3,4-difluorophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(F)C(F)=CC=2)=C1C(=O)OC XCXIVLCMRKWWQY-UHFFFAOYSA-N 0.000 description 2
- UTLYGYNJWOAWHK-UHFFFAOYSA-N methyl 5-(3,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(C)C(C)=CC=2)=C1C(=O)OC UTLYGYNJWOAWHK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- WENOQBZLHQRYHF-UHFFFAOYSA-N methyl 5-(3-bromo-4-fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(Br)C(F)=CC=2)=C1C(=O)OC WENOQBZLHQRYHF-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 2
- 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 2
- 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 2
- 230000000926 neurological effect Effects 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- GYHFUZHODSMOHU-UHFFFAOYSA-N nonanal Chemical compound CCCCCCCCC=O GYHFUZHODSMOHU-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- OHOWSYIKESXDMN-WMQZXSDYSA-N orexin-b Chemical compound C([C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCSC)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(N)=O)C1=CNC=N1 OHOWSYIKESXDMN-WMQZXSDYSA-N 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 2
- 208000019906 panic disease Diseases 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 201000004193 respiratory failure Diseases 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 208000020685 sleep-wake disease Diseases 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- SORUJRRDPAXNTE-BZSNNMDCSA-N tert-butyl (2s,3as,6as)-2-[(benzylamino)methyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrole-1-carboxylate Chemical compound C([C@H]1N([C@H]2CCC[C@H]2C1)C(=O)OC(C)(C)C)NCC1=CC=CC=C1 SORUJRRDPAXNTE-BZSNNMDCSA-N 0.000 description 2
- VCXMYSMZPWADMK-DCAQKATOSA-N tert-butyl (2s,3as,6as)-2-formyl-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrole-1-carboxylate Chemical compound C1CC[C@@H]2N(C(=O)OC(C)(C)C)[C@H](C=O)C[C@@H]21 VCXMYSMZPWADMK-DCAQKATOSA-N 0.000 description 2
- OQHKEWIEKYQINX-ACZMJKKPSA-N (2s,3as,6as)-1,2,3,3a,4,5,6,6a-octahydrocyclopenta[b]pyrrol-1-ium-2-carboxylate Chemical compound C1CC[C@@H]2N[C@H](C(=O)O)C[C@@H]21 OQHKEWIEKYQINX-ACZMJKKPSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- WFAPIZKLEVLUMX-UHFFFAOYSA-N 1-benzofuran-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1C=CO2 WFAPIZKLEVLUMX-UHFFFAOYSA-N 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- GISVICWQYMUPJF-UHFFFAOYSA-N 2,4-Dimethylbenzaldehyde Chemical compound CC1=CC=C(C=O)C(C)=C1 GISVICWQYMUPJF-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical class CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- AKZBGCSSXWJAGL-UHFFFAOYSA-N 2-amino-5-(4-methylphenyl)-1,3-thiazole-4-carboxylic acid Chemical compound C1=CC(C)=CC=C1C1=C(C(O)=O)N=C(N)S1 AKZBGCSSXWJAGL-UHFFFAOYSA-N 0.000 description 1
- LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
- FMZQBJUJTDAWOW-UHFFFAOYSA-N 2-bromo-3-oxobutanoic acid Chemical compound CC(=O)C(Br)C(O)=O FMZQBJUJTDAWOW-UHFFFAOYSA-N 0.000 description 1
- KKAGLBKKRQQAKU-UHFFFAOYSA-N 2-cyclopropyl-5-(4-fluorophenyl)-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C=1N=C(C2CC2)SC=1C1=CC=C(F)C=C1 KKAGLBKKRQQAKU-UHFFFAOYSA-N 0.000 description 1
- NMHVFLAFNJUKQU-UHFFFAOYSA-N 2-cyclopropyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C=1N=C(C2CC2)SC=1C1=CC=CC(C(F)(F)F)=C1 NMHVFLAFNJUKQU-UHFFFAOYSA-N 0.000 description 1
- ZIELJULESAVIDW-UHFFFAOYSA-N 2-cyclopropyl-5-phenyl-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C=1N=C(C2CC2)SC=1C1=CC=CC=C1 ZIELJULESAVIDW-UHFFFAOYSA-N 0.000 description 1
- LBVIWYRIQOZIRO-UHFFFAOYSA-N 2-hydroxyimino-3-oxobutanoic acid Chemical compound CC(=O)C(=NO)C(O)=O LBVIWYRIQOZIRO-UHFFFAOYSA-N 0.000 description 1
- DHUFXBJQFCCELL-UHFFFAOYSA-N 2-methyl-5-(3-methylphenyl)-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=CC(C)=C1 DHUFXBJQFCCELL-UHFFFAOYSA-N 0.000 description 1
- YFOICSSNYXWWBW-UHFFFAOYSA-N 2-methyl-5-(4-methylphenyl)-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=C(C)C=C1 YFOICSSNYXWWBW-UHFFFAOYSA-N 0.000 description 1
- MAYJMHQNYBDRTN-UHFFFAOYSA-N 2-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=CC(C(F)(F)F)=C1 MAYJMHQNYBDRTN-UHFFFAOYSA-N 0.000 description 1
- IUPHMHDVSPSLME-UHFFFAOYSA-N 2-methyl-5-phenyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=CC=C1 IUPHMHDVSPSLME-UHFFFAOYSA-N 0.000 description 1
- POQJHLBMLVTHAU-UHFFFAOYSA-N 3,4-Dimethylbenzaldehyde Chemical compound CC1=CC=C(C=O)C=C1C POQJHLBMLVTHAU-UHFFFAOYSA-N 0.000 description 1
- ZWUSBSHBFFPRNE-UHFFFAOYSA-N 3,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Cl ZWUSBSHBFFPRNE-UHFFFAOYSA-N 0.000 description 1
- JPHKMYXKNKLNDF-UHFFFAOYSA-N 3,4-difluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1F JPHKMYXKNKLNDF-UHFFFAOYSA-N 0.000 description 1
- NBEFMISJJNGCIZ-UHFFFAOYSA-N 3,5-dimethylbenzaldehyde Chemical compound CC1=CC(C)=CC(C=O)=C1 NBEFMISJJNGCIZ-UHFFFAOYSA-N 0.000 description 1
- NMTUHPSKJJYGML-UHFFFAOYSA-N 3-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(C=O)=C1 NMTUHPSKJJYGML-UHFFFAOYSA-N 0.000 description 1
- ONZQYZKCUHFORE-UHFFFAOYSA-N 3-bromo-1,1,1-trifluoropropan-2-one Chemical compound FC(F)(F)C(=O)CBr ONZQYZKCUHFORE-UHFFFAOYSA-N 0.000 description 1
- FAHZIKXYYRGSHF-UHFFFAOYSA-N 3-bromo-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1Br FAHZIKXYYRGSHF-UHFFFAOYSA-N 0.000 description 1
- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- PIKNVEVCWAAOMJ-UHFFFAOYSA-N 3-fluorobenzaldehyde Chemical compound FC1=CC=CC(C=O)=C1 PIKNVEVCWAAOMJ-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- YGDQLEYCBFGWDH-UHFFFAOYSA-N 5-(2,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=C(C)C=C1C YGDQLEYCBFGWDH-UHFFFAOYSA-N 0.000 description 1
- LXMLVJXSPWAAGN-UHFFFAOYSA-N 5-(3,4-dichlorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=C(Cl)C(Cl)=C1 LXMLVJXSPWAAGN-UHFFFAOYSA-N 0.000 description 1
- LDAOPPHUSNWEPT-UHFFFAOYSA-N 5-(3,4-difluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=C(F)C(F)=C1 LDAOPPHUSNWEPT-UHFFFAOYSA-N 0.000 description 1
- DPSUBMCVJKVLQV-UHFFFAOYSA-N 5-(3,4-dimethylphenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=C(C)C(C)=C1 DPSUBMCVJKVLQV-UHFFFAOYSA-N 0.000 description 1
- QCRPADQSLWRMAE-UHFFFAOYSA-N 5-(3-acetamidophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound CC(=O)NC1=CC=CC(C2=C(N=C(C)S2)C(O)=O)=C1 QCRPADQSLWRMAE-UHFFFAOYSA-N 0.000 description 1
- MRLLVACQABUSKY-UHFFFAOYSA-N 5-(3-bromo-4-fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=C(F)C(Br)=C1 MRLLVACQABUSKY-UHFFFAOYSA-N 0.000 description 1
- UKTAGVSEPAZCCQ-UHFFFAOYSA-N 5-(3-chlorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=CC(Cl)=C1 UKTAGVSEPAZCCQ-UHFFFAOYSA-N 0.000 description 1
- GCBMFDPCVMRYRN-UHFFFAOYSA-N 5-(3-fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=CC(F)=C1 GCBMFDPCVMRYRN-UHFFFAOYSA-N 0.000 description 1
- AWYYUQSAFYQARO-UHFFFAOYSA-N 5-(4-bromophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=C(Br)C=C1 AWYYUQSAFYQARO-UHFFFAOYSA-N 0.000 description 1
- XYIAPLYZWWLUBC-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C)=NC(C(O)=O)=C1C1=CC=C(F)C=C1 XYIAPLYZWWLUBC-UHFFFAOYSA-N 0.000 description 1
- GUABFMPMKJGSBQ-UHFFFAOYSA-N 5-methyl-1,3-thiazol-2-amine Chemical compound CC1=CN=C(N)S1 GUABFMPMKJGSBQ-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 201000000736 Amenorrhea Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010002653 Anosmia Diseases 0.000 description 1
- 208000025978 Athletic injury Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 201000009586 Basophil Adenoma Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 208000002381 Brain Hypoxia Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- QFFWAVCSBQDOTG-OYAYLOLSSA-N CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC(Cl)=C2Cl)S1.OC(C1=C(CCO2)C2=CC=C1)=O Chemical compound CC1=NC(C(N2[C@@H](CCC3)[C@@H]3C[C@H]2CN)=O)=C(C(C=C2)=CC(Cl)=C2Cl)S1.OC(C1=C(CCO2)C2=CC=C1)=O QFFWAVCSBQDOTG-OYAYLOLSSA-N 0.000 description 1
- 101150084740 CFAP126 gene Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000009810 Catatonic Schizophrenia Diseases 0.000 description 1
- 208000001387 Causalgia Diseases 0.000 description 1
- GAUKCDPSYQUYQL-UHFFFAOYSA-N Cc1n[o]c2c1cccc2 Chemical compound Cc1n[o]c2c1cccc2 GAUKCDPSYQUYQL-UHFFFAOYSA-N 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 1
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 1
- 208000033001 Complex partial seizures Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 206010012218 Delirium Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 206010013754 Drug withdrawal syndrome Diseases 0.000 description 1
- 206010013883 Dwarfism Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 208000002091 Febrile Seizures Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 206010018265 Gigantism Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 101000598921 Homo sapiens Orexin Proteins 0.000 description 1
- 101500025902 Homo sapiens Orexin-A Proteins 0.000 description 1
- 206010020400 Hostility Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000004454 Hyperalgesia Diseases 0.000 description 1
- 208000035154 Hyperesthesia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 201000001916 Hypochondriasis Diseases 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 208000028482 Hypothalamic disease Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 201000007493 Kallmann syndrome Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- 201000006792 Lennox-Gastaut syndrome Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 206010029333 Neurosis Diseases 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 206010053142 Olfacto genital dysplasia Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010033864 Paranoia Diseases 0.000 description 1
- 208000027099 Paranoid disease Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000014993 Pituitary disease Diseases 0.000 description 1
- 206010036832 Prolactinoma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102100039031 Protein Flattop Human genes 0.000 description 1
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010038669 Respiratory arrest Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 208000036754 Schizophrenia, catatonic type Diseases 0.000 description 1
- 208000010340 Sleep Deprivation Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000027520 Somatoform disease Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000011622 Testicular disease Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 206010046555 Urinary retention Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 231100000540 amenorrhea Toxicity 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 235000019558 anosmia Nutrition 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 208000008784 apnea Diseases 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- HLXCXOQXUDRJLF-JKBZPBJLSA-N benzyl (2s,3as,6as)-1,2,3,3a,4,5,6,6a-octahydrocyclopenta[b]pyrrole-2-carboxylate;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@H]2CCC[C@H]2C1)OCC1=CC=CC=C1 HLXCXOQXUDRJLF-JKBZPBJLSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 150000003938 benzyl alcohols Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 230000027288 circadian rhythm Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- CFMRIVVTGARDJZ-UHFFFAOYSA-N cyclopropyltin Chemical class [Sn]C1CC1 CFMRIVVTGARDJZ-UHFFFAOYSA-N 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 235000021061 dietary behavior Nutrition 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 206010013461 dissociative amnesia Diseases 0.000 description 1
- 208000018459 dissociative disease Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 208000009985 drug-induced dyskinesia Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000030135 gastric motility Effects 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 230000006589 gland dysfunction Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 208000031424 hyperprolactinemia Diseases 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 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
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 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
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 230000036630 mental development Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- KUWWRNNYEYGSBQ-UHFFFAOYSA-N methyl 1,3-thiazole-4-carboxylate Chemical class COC(=O)C1=CSC=N1 KUWWRNNYEYGSBQ-UHFFFAOYSA-N 0.000 description 1
- WYVZZWKIKAKUKV-UHFFFAOYSA-N methyl 2-amino-1,3-thiazole-4-carboxylate Chemical class COC(=O)C1=CSC(N)=N1 WYVZZWKIKAKUKV-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
- YOWKNNKTQWCYNC-UHFFFAOYSA-N methyl 2-bromo-1,3-thiazole-4-carboxylate Chemical class COC(=O)C1=CSC(Br)=N1 YOWKNNKTQWCYNC-UHFFFAOYSA-N 0.000 description 1
- GYQRIAVRKLRQKP-UHFFFAOYSA-N methyl 2-chloro-3-oxobutanoate Chemical compound COC(=O)C(Cl)C(C)=O GYQRIAVRKLRQKP-UHFFFAOYSA-N 0.000 description 1
- NRGLPUBJIJZGIG-UHFFFAOYSA-N methyl 5-(3,5-dimethylphenyl)-2-methyl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C)SC(C=2C=C(C)C=C(C)C=2)=C1C(=O)OC NRGLPUBJIJZGIG-UHFFFAOYSA-N 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 201000003152 motion sickness Diseases 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 208000027753 pain disease Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 208000033300 perinatal asphyxia Diseases 0.000 description 1
- 208000030062 persistent idiopathic facial pain Diseases 0.000 description 1
- 208000022821 personality disease Diseases 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 208000020351 pituitary gland basophil adenoma Diseases 0.000 description 1
- 208000017402 pituitary gland disease Diseases 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 229940116357 potassium thiocyanate Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 208000030153 prolactin-producing pituitary gland adenoma Diseases 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical class CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001107 psychogenic effect Effects 0.000 description 1
- 208000026961 psychosexual disease Diseases 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 208000022610 schizoaffective disease Diseases 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 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
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FOBQQKXFENJDEL-DCAQKATOSA-N tert-butyl (2s,3as,6as)-2-(hydroxymethyl)-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrole-1-carboxylate Chemical compound C1CC[C@@H]2N(C(=O)OC(C)(C)C)[C@H](CO)C[C@@H]21 FOBQQKXFENJDEL-DCAQKATOSA-N 0.000 description 1
- QJJKOLVFCJYBMZ-DZKIICNBSA-N tert-butyl (2s,3as,6as)-2-[(1,2-benzoxazole-3-carbonylamino)methyl]-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]pyrrole-1-carboxylate Chemical compound C1=CC=C2C(C(=O)NC[C@H]3N([C@H]4CCC[C@H]4C3)C(=O)OC(C)(C)C)=NOC2=C1 QJJKOLVFCJYBMZ-DZKIICNBSA-N 0.000 description 1
- YIAGIPUMQSTQNW-UHFFFAOYSA-N tert-butyl 2-methyloctanoate Chemical compound CCCCCCC(C)C(=O)OC(C)(C)C YIAGIPUMQSTQNW-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 231100000886 tinnitus Toxicity 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- RUCOUXAHBYBPHL-UHFFFAOYSA-N tributyl(cyclopropyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1CC1 RUCOUXAHBYBPHL-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Child & Adolescent Psychology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IB2007052991 | 2007-07-27 | ||
| IBPCT/IB2007/052991 | 2007-07-27 | ||
| PCT/IB2008/052989 WO2009016564A2 (en) | 2007-07-27 | 2008-07-25 | 2-aza-bicyclo[3.3.0]octane derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2010106854A RU2010106854A (ru) | 2011-09-10 |
| RU2478099C2 true RU2478099C2 (ru) | 2013-03-27 |
Family
ID=40174799
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2010106854/04A RU2478099C2 (ru) | 2007-07-27 | 2008-07-25 | Производные 2-аза-бицикло[3.3.0]октана |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8288429B2 (enExample) |
| EP (1) | EP2183246A2 (enExample) |
| JP (1) | JP2010534647A (enExample) |
| KR (1) | KR20100046047A (enExample) |
| CN (1) | CN101874028B (enExample) |
| AU (1) | AU2008281399A1 (enExample) |
| BR (1) | BRPI0814593A2 (enExample) |
| CA (1) | CA2693820A1 (enExample) |
| MA (1) | MA31593B1 (enExample) |
| NZ (1) | NZ583487A (enExample) |
| RU (1) | RU2478099C2 (enExample) |
| WO (1) | WO2009016564A2 (enExample) |
| ZA (1) | ZA201001434B (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CL2007002809A1 (es) * | 2006-09-29 | 2008-04-18 | Actelion Pharmaceuticals Ltd | Compuestos derivados de 3-aza biciclo [3.1.0]hexano; y su uso en el tratamiento de enfermedades tales como desordenes psicoticos y de ansiedad, desordenes del sueno, uso y abuso de sustancias psicoactivas, demencia y deterioro de funciones cognitivas |
| CN101568533A (zh) | 2006-12-01 | 2009-10-28 | 埃科特莱茵药品有限公司 | 3-异芳基(氨基或酰胺基)-1-(联苯或苯基噻唑基)羰基哌啶衍生物食欲素受体抑制剂 |
| AR064561A1 (es) * | 2006-12-28 | 2009-04-08 | Actelion Pharmaceuticals Ltd | Derivados de 2-aza-biciclo[3.1.0]hexano y su uso en la preparacion de un medicamento para el tratamiento de enfermedades relacionadas con disfunciones generales del sistema de la orexina. |
| 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. |
| US8030495B2 (en) | 2007-05-23 | 2011-10-04 | Coleman Paul J | Cyclopropyl pyrrolidine orexin receptor antagonists |
| US8106215B2 (en) * | 2007-07-03 | 2012-01-31 | Actelion Pharmaceuticals Ltd. | 3-aza-bicyclo[3.3.0]octane compounds |
| US8288411B2 (en) * | 2007-09-24 | 2012-10-16 | Actelion Pharmaceuticals Ltd. | Pyrrolidines and piperidines as orexin receptor antagonists |
| AU2009215243A1 (en) * | 2008-02-21 | 2009-08-27 | Actelion Pharmaceuticals Ltd. | 2-aza-bicyclo[2.2.1]heptane derivatives |
| JP2011519849A (ja) * | 2008-04-30 | 2011-07-14 | アクテリオン ファーマシューティカルズ リミテッド | ピペリジン及びピロリジン化合物 |
| RU2011119217A (ru) * | 2008-10-14 | 2012-11-27 | Актелион Фармасьютикалз Лтд | Производные фенетиламида и их гетероциклические аналоги |
| ME03452B (me) | 2009-10-23 | 2020-01-20 | Janssen Pharmaceutica Nv | Disupstituisani oktahi-dropirolo[3,4-c]piroli kao modulatori oreksin receptora |
| ES2552932T3 (es) * | 2009-12-29 | 2015-12-03 | Suven Life Sciences Limited | Ligandos del receptor nicotínico neuronal de la acetilcolina alfa4beta2 |
| CA2788450A1 (en) | 2009-12-30 | 2011-07-07 | Arqule, Inc. | Substituted naphthalenyl-pyrimidine compounds |
| JP6346862B2 (ja) | 2012-02-07 | 2018-06-20 | エオラス セラピューティクス， インコーポレイテッド | オレキシンレセプターアンタゴニストとしての置換プロリン／ピペリジン |
| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| ITMI20120424A1 (it) | 2012-03-19 | 2013-09-20 | Rottapharm Spa | Composti chimici |
| DK2855453T3 (en) | 2012-06-04 | 2017-02-06 | Actelion Pharmaceuticals Ltd | Benzimidazol-proline derivatives |
| BR112015007516A2 (pt) | 2012-10-10 | 2017-07-04 | Actelion Pharmaceuticals Ltd | antagonistas do receptor de orexina que são derivados de [orto bi-(hetero-)aril]-[2-(meta bi-(hetero-)aril)- pirrolidin-1-il]-metanona |
| CN105051040A (zh) | 2013-03-12 | 2015-11-11 | 埃科特莱茵药品有限公司 | 作为食欲素受体拮抗剂的氮杂环丁烷酰胺衍生物 |
| UA119151C2 (uk) | 2013-12-03 | 2019-05-10 | Ідорсія Фармасьютікалз Лтд | КРИСТАЛІЧНА СОЛЬОВА ФОРМА (S)-(2-(6-ХЛОР-7-МЕТИЛ-1H-БЕНЗО[d]ІМІДАЗОЛ-2-ІЛ)-2-МЕТИЛПІРОЛІДИН-1-ІЛ)(5-МЕТОКСИ-2-(2H-1,2,3-ТРИАЗОЛ-2-ІЛ)ФЕНІЛ)МЕТАНОНУ ЯК АНТАГОНІСТ ОРЕКСИНОВОГО РЕЦЕПТОРА |
| CN105793257B (zh) | 2013-12-03 | 2018-11-13 | 爱杜西亚药品有限公司 | 苯并咪唑环化合物的晶形及其用途 |
| SI3077391T1 (sl) | 2013-12-04 | 2018-11-30 | Idorsia Pharmaceuticals Ltd | Uporaba benzimidazol-prolinskih derivatov |
| TW201613902A (en) | 2014-08-13 | 2016-04-16 | Eolas Therapeutics Inc | Difluoropyrrolidines as orexin receptor modulators |
| US10894789B2 (en) | 2016-02-12 | 2021-01-19 | Astrazeneca Ab | Halo-substituted piperidines as orexin receptor modulators |
| KR20230116948A (ko) | 2016-03-10 | 2023-08-04 | 얀센 파마슈티카 엔.브이. | 오렉신-2 수용체 길항제를 사용한 우울증의 치료 방법 |
| EP3454857A1 (en) | 2016-05-10 | 2019-03-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of autoimmune inflammatory diseases |
| GB201618181D0 (en) | 2016-10-27 | 2016-12-14 | J Banks & Co Ltd | Slide turn door assembly and support mechanism therefor |
| WO2020007964A1 (en) | 2018-07-05 | 2020-01-09 | Idorsia Pharmaceuticals Ltd | 2-(2-azabicyclo[3.1.0]hexan-1-yl)-1h-benzimidazole derivatives |
| WO2020099511A1 (en) | 2018-11-14 | 2020-05-22 | Idorsia Pharmaceuticals Ltd | Benzimidazole-2-methyl-morpholine derivatives |
| WO2022040058A1 (en) | 2020-08-18 | 2022-02-24 | Merck Sharp & Dohme Corp. | Cyclopentapyrrole orexin receptor agonists |
| WO2023218023A1 (en) | 2022-05-13 | 2023-11-16 | Idorsia Pharmaceuticals Ltd | Thiazoloaryl-methyl substituted cyclic hydrazine-n-carboxamide derivatives |
| WO2025224168A1 (en) | 2024-04-24 | 2025-10-30 | Idorsia Pharmaceuticals Ltd | Aryl sulfone and sulfanone derivatives as orexin receptor modulators |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1676451A3 (ru) * | 1987-09-23 | 1991-09-07 | Иституто Де Анджели С.П.А. (Фирма) | Способ получени производных бензимидазола в виде смеси изомеров или индивидуальных изомеров в свободном виде или в виде их физиологически приемлемых солей |
| RU2135503C1 (ru) * | 1992-06-19 | 1999-08-27 | Басф Акциенгезельшафт | N-замещенные производные 3-азабицикло (3.2.0)гептана или их соли с физиологически совместимыми кислотами |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57139032A (en) | 1981-02-20 | 1982-08-27 | Takasago Corp | 2-(butan-2-on-3-yl)-5-methylphenol and perfumery composition containing the same |
| GB9319732D0 (en) * | 1993-09-24 | 1993-11-10 | Ucb Sa | Use of (s)-alpha-ethyl-2-oxo-l-pyrrolidineacetamide for the treatment of anxiety |
| WO1995029922A1 (en) | 1994-04-29 | 1995-11-09 | Pharmacia & Upjohn Company | Methanol derivatives for treatment of retroviral infections especially hiv infections |
| EP1289955B1 (en) | 2000-06-16 | 2005-04-13 | Smithkline Beecham Plc | Piperidines for use as orexin receptor antagonists |
| US7244721B2 (en) | 2000-07-21 | 2007-07-17 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
| EP1353918B1 (en) | 2000-11-28 | 2005-01-12 | Smithkline Beecham Plc | Morpholine derivatives as antagonists of orexin receptors |
| US20040192673A1 (en) | 2001-05-05 | 2004-09-30 | Pascale Gaillard | N-aroyl cyclic amine derivatives as orexin receptor antagonists |
| BR0209334A (pt) | 2001-05-05 | 2004-06-15 | Smithkline Beecham Plc | Aminas n-aroil cìclicas |
| US7470710B2 (en) | 2001-06-28 | 2008-12-30 | Smithkline Beecham P.L.C. | N-aroyl cyclic amine derivatives as orexin receptor antagonists |
| GB0115862D0 (en) | 2001-06-28 | 2001-08-22 | Smithkline Beecham Plc | Compounds |
| GB0124463D0 (en) | 2001-10-11 | 2001-12-05 | Smithkline Beecham Plc | Compounds |
| GB0127145D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Compounds |
| GB0130335D0 (en) | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| GB0130393D0 (en) | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| WO2004026866A1 (en) | 2002-09-18 | 2004-04-01 | Glaxo Group Limited | N-aroyl cyclic amines as orexin receptor antagonists |
| CA2499128C (en) | 2002-09-25 | 2012-07-31 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof |
| GB0225944D0 (en) | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| GB0225938D0 (en) | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| GB0225884D0 (en) | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| WO2005092890A2 (en) | 2004-03-25 | 2005-10-06 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| US20060014733A1 (en) | 2004-07-19 | 2006-01-19 | Pfizer Inc | Histamine-3 agonists and antagonists |
| CL2007002809A1 (es) * | 2006-09-29 | 2008-04-18 | Actelion Pharmaceuticals Ltd | Compuestos derivados de 3-aza biciclo [3.1.0]hexano; y su uso en el tratamiento de enfermedades tales como desordenes psicoticos y de ansiedad, desordenes del sueno, uso y abuso de sustancias psicoactivas, demencia y deterioro de funciones cognitivas |
| CN101568533A (zh) * | 2006-12-01 | 2009-10-28 | 埃科特莱茵药品有限公司 | 3-异芳基(氨基或酰胺基)-1-(联苯或苯基噻唑基)羰基哌啶衍生物食欲素受体抑制剂 |
| 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 |
| US8030495B2 (en) | 2007-05-23 | 2011-10-04 | Coleman Paul J | Cyclopropyl pyrrolidine orexin receptor antagonists |
| HRP20120240T1 (hr) * | 2007-05-23 | 2012-04-30 | Merck Sharp & Dohme Corp. | Piridil piperidin antagonisti receptora za oreksin |
| GB0712888D0 (en) * | 2007-07-03 | 2007-08-15 | Glaxo Group Ltd | Novel compounds |
| EP2176258A1 (en) * | 2007-07-03 | 2010-04-21 | Glaxo Group Limited | Piperidine derivatives useful as orexin receptor antagonists |
| AR067665A1 (es) * | 2007-07-27 | 2009-10-21 | Actelion Pharmaceuticals Ltd | Derivados de trans-3- aza-biciclo ( 3.1.0) hexano |
| US8288411B2 (en) * | 2007-09-24 | 2012-10-16 | Actelion Pharmaceuticals Ltd. | Pyrrolidines and piperidines as orexin receptor antagonists |
| KR101204213B1 (ko) * | 2007-12-21 | 2012-11-26 | 에프. 호프만-라 로슈 아게 | 오렉신 수용체 길항제로서의 헤테로아릴 유도체 |
| AU2009215243A1 (en) * | 2008-02-21 | 2009-08-27 | Actelion Pharmaceuticals Ltd. | 2-aza-bicyclo[2.2.1]heptane derivatives |
| JP2011519849A (ja) * | 2008-04-30 | 2011-07-14 | アクテリオン ファーマシューティカルズ リミテッド | ピペリジン及びピロリジン化合物 |
| AU2009249306B8 (en) | 2008-05-22 | 2013-07-25 | Merck Canada Inc. | Process for the preparation of an orexin receptor antagonist |
-
2008
- 2008-07-25 KR KR1020107004524A patent/KR20100046047A/ko not_active Withdrawn
- 2008-07-25 US US12/670,823 patent/US8288429B2/en not_active Expired - Fee Related
- 2008-07-25 RU RU2010106854/04A patent/RU2478099C2/ru not_active IP Right Cessation
- 2008-07-25 NZ NZ583487A patent/NZ583487A/en not_active IP Right Cessation
- 2008-07-25 CN CN200880100389XA patent/CN101874028B/zh not_active Expired - Fee Related
- 2008-07-25 CA CA2693820A patent/CA2693820A1/en not_active Abandoned
- 2008-07-25 AU AU2008281399A patent/AU2008281399A1/en not_active Abandoned
- 2008-07-25 WO PCT/IB2008/052989 patent/WO2009016564A2/en not_active Ceased
- 2008-07-25 JP JP2010517536A patent/JP2010534647A/ja active Pending
- 2008-07-25 BR BRPI0814593-8A2A patent/BRPI0814593A2/pt not_active IP Right Cessation
- 2008-07-25 EP EP08789443A patent/EP2183246A2/en not_active Withdrawn
-
2010
- 2010-02-05 MA MA32589A patent/MA31593B1/fr unknown
- 2010-02-26 ZA ZA2010/01434A patent/ZA201001434B/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1676451A3 (ru) * | 1987-09-23 | 1991-09-07 | Иституто Де Анджели С.П.А. (Фирма) | Способ получени производных бензимидазола в виде смеси изомеров или индивидуальных изомеров в свободном виде или в виде их физиологически приемлемых солей |
| RU2135503C1 (ru) * | 1992-06-19 | 1999-08-27 | Басф Акциенгезельшафт | N-замещенные производные 3-азабицикло (3.2.0)гептана или их соли с физиологически совместимыми кислотами |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009016564A2 (en) | 2009-02-05 |
| EP2183246A2 (en) | 2010-05-12 |
| JP2010534647A (ja) | 2010-11-11 |
| CN101874028B (zh) | 2012-11-14 |
| ZA201001434B (en) | 2013-08-28 |
| CA2693820A1 (en) | 2009-02-05 |
| MA31593B1 (fr) | 2010-08-02 |
| BRPI0814593A2 (pt) | 2015-01-20 |
| CN101874028A (zh) | 2010-10-27 |
| NZ583487A (en) | 2011-09-30 |
| RU2010106854A (ru) | 2011-09-10 |
| WO2009016564A3 (en) | 2009-03-26 |
| US8288429B2 (en) | 2012-10-16 |
| US20110009461A1 (en) | 2011-01-13 |
| AU2008281399A1 (en) | 2009-02-05 |
| KR20100046047A (ko) | 2010-05-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8288429B2 (en) | 2-aza-bicyclo[3.3.0]octane derivatives | |
| EP2247586B1 (en) | 2-aza-bicyclo[2.2.1]heptane derivatives | |
| US8288411B2 (en) | Pyrrolidines and piperidines as orexin receptor antagonists | |
| US8288435B2 (en) | 2-aza-bicyclo[3.1.0]hexane derivatives as orexin receptor antagonists | |
| EP2318367B1 (en) | Piperidine and pyrrolidine compounds | |
| US20100222328A1 (en) | 2-cyclopropyl-thiazole derivatives | |
| US20100016401A1 (en) | 3-aza-bicyclo[3.1.0]hexane derivatives | |
| US20110086889A1 (en) | Tetrazole compounds as orexin receptor antagonists | |
| KR20100041805A (ko) | 3-아자-비시클로[3.3.0]옥탄 화합물 | |
| WO2008087611A2 (en) | Pyrrolidine- and piperidine- bis-amide derivatives | |
| JP2008524325A (ja) | 複素環式ＭＣＨｒ１アンタゴニストと療法におけるその使用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20130726 |