EA016234B1 - ЗАМЕЩЕННЫЕ 2,3,4,5-ТЕТРАГИДРО-1Н-ПИРИДО[4,3-b]ИНДОЛЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ - Google Patents

Info

Publication number

EA016234B1

EA016234B1 EA200901253A EA200901253A EA016234B1 EA 016234 B1 EA016234 B1 EA 016234B1 EA 200901253 A EA200901253 A EA 200901253A EA 200901253 A EA200901253 A EA 200901253A EA 016234 B1 EA016234 B1 EA 016234B1

Authority

EA

Eurasian Patent Office

Prior art keywords

tetrahydro

pyrido

indole

methyl

pyridin

Prior art date

2007-04-05

Links

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• 150000008591 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles Chemical class 0.000 title claims abstract description 24
• 238000000034 method Methods 0.000 title claims abstract description 24
• 238000004519 manufacturing process Methods 0.000 title description 7
• 150000001875 compounds Chemical class 0.000 claims abstract description 67
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 58
• 239000005557 antagonist Substances 0.000 claims abstract description 50
• 125000001424 substituent group Chemical group 0.000 claims abstract description 48
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 29
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 29
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 26
• BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims abstract description 24
• 229910001424 calcium ion Inorganic materials 0.000 claims abstract description 24
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 21
• 150000002367 halogens Chemical class 0.000 claims abstract description 20
• 230000013632 homeostatic process Effects 0.000 claims abstract description 19
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 18
• 239000001257 hydrogen Substances 0.000 claims abstract description 13
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims abstract description 3
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 140
• -1 2-phenylvinyl Chemical group 0.000 claims description 131
• 150000003839 salts Chemical class 0.000 claims description 66
• 102000005962 receptors Human genes 0.000 claims description 48
• 108020003175 receptors Proteins 0.000 claims description 48
• 239000003814 drug Substances 0.000 claims description 44
• 238000011282 treatment Methods 0.000 claims description 37
• 239000011575 calcium Substances 0.000 claims description 36
• 229940079593 drug Drugs 0.000 claims description 32
• 229910052757 nitrogen Inorganic materials 0.000 claims description 31
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
• 241001465754 Metazoa Species 0.000 claims description 25
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
• 150000004677 hydrates Chemical class 0.000 claims description 24
• 229940076279 serotonin Drugs 0.000 claims description 24
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 22
• 150000002475 indoles Chemical class 0.000 claims description 22
• 229920002554 vinyl polymer Polymers 0.000 claims description 22
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
• 201000010099 disease Diseases 0.000 claims description 18
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• 125000004429 atom Chemical group 0.000 claims description 14
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• 230000001777 nootropic effect Effects 0.000 claims description 13
• 239000003826 tablet Substances 0.000 claims description 13
• 201000000980 schizophrenia Diseases 0.000 claims description 12
• 239000002904 solvent Substances 0.000 claims description 12
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
• 208000019901 Anxiety disease Diseases 0.000 claims description 11
• 239000002775 capsule Substances 0.000 claims description 11
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 11
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 11
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
• 108091005435 5-HT6 receptors Proteins 0.000 claims description 9
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• 239000000935 antidepressant agent Substances 0.000 claims description 9
• 229940005513 antidepressants Drugs 0.000 claims description 9
• 230000000949 anxiolytic effect Effects 0.000 claims description 9
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 9
• 230000002936 tranquilizing effect Effects 0.000 claims description 9
• 239000002249 anxiolytic agent Substances 0.000 claims description 8
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
• XBVCLWSNUNVPNC-UHFFFAOYSA-N 2-methyl-5-(2-pyridin-3-ylethynyl)-8-(trifluoromethyl)-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(C(F)(F)F)=CC=C1N2C#CC1=CC=CN=C1 XBVCLWSNUNVPNC-UHFFFAOYSA-N 0.000 claims description 7
• IWEWIZBBORJKBV-UHFFFAOYSA-N 8-fluoro-2-methyl-5-(2-phenylethyl)-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(F)=CC=C1N2CCC1=CC=CC=C1 IWEWIZBBORJKBV-UHFFFAOYSA-N 0.000 claims description 7
• 150000002500 ions Chemical class 0.000 claims description 7
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• XQDRWCFJBHLWPR-JLHYYAGUSA-N 2,8-dimethyl-5-[(e)-2-phenylethenyl]-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2\C=C\C1=CC=CC=C1 XQDRWCFJBHLWPR-JLHYYAGUSA-N 0.000 claims description 6
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• OORNIOGZQUYGRW-UHFFFAOYSA-N 8-fluoro-2-methyl-5-(2-pyridin-2-ylethyl)-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(F)=CC=C1N2CCC1=CC=CC=N1 OORNIOGZQUYGRW-UHFFFAOYSA-N 0.000 claims description 6
• CZCOISNXSIJAAK-UHFFFAOYSA-N 8-fluoro-2-methyl-5-(2-pyridin-3-ylethyl)-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(F)=CC=C1N2CCC1=CC=CN=C1 CZCOISNXSIJAAK-UHFFFAOYSA-N 0.000 claims description 6
• PRSVXRUERNSVCI-UHFFFAOYSA-N 8-fluoro-2-methyl-5-(2-pyridin-4-ylethyl)-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(F)=CC=C1N2CCC1=CC=NC=C1 PRSVXRUERNSVCI-UHFFFAOYSA-N 0.000 claims description 6
• RZNJWVKDPLJHOA-IZZDOVSWSA-N 8-fluoro-2-methyl-5-[(e)-2-pyridin-4-ylethenyl]-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(F)=CC=C1N2\C=C\C1=CC=NC=C1 RZNJWVKDPLJHOA-IZZDOVSWSA-N 0.000 claims description 6
• 229910052786 argon Inorganic materials 0.000 claims description 6
• JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 claims description 6
• 230000008506 pathogenesis Effects 0.000 claims description 6
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• LZUIBAORLZILET-FMIVXFBMSA-N 2,8-dimethyl-5-[(e)-2-[4-(trifluoromethyl)phenyl]ethenyl]-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2\C=C\C1=CC=C(C(F)(F)F)C=C1 LZUIBAORLZILET-FMIVXFBMSA-N 0.000 claims description 5
• ZBNYHEVTJCAGAE-KPKJPENVSA-N 2,8-dimethyl-5-[(e)-2-pyridin-4-ylethenyl]-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2\C=C\C1=CC=NC=C1 ZBNYHEVTJCAGAE-KPKJPENVSA-N 0.000 claims description 5
• KPGWZRTZTASLIF-UHFFFAOYSA-N 2-methyl-5-(2-phenylethyl)-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC=CC=C1N2CCC1=CC=CC=C1 KPGWZRTZTASLIF-UHFFFAOYSA-N 0.000 claims description 5
• VATMTSNDTTWBHN-UHFFFAOYSA-N 2-methyl-5-(2-phenylethyl)-6-(trifluoromethyl)-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC=CC(C(F)(F)F)=C1N2CCC1=CC=CC=C1 VATMTSNDTTWBHN-UHFFFAOYSA-N 0.000 claims description 5
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• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 5
• SLKYZAGABKKIDN-FMIVXFBMSA-N 5-[(e)-2-(4-fluorophenyl)ethenyl]-2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2\C=C\C1=CC=C(F)C=C1 SLKYZAGABKKIDN-FMIVXFBMSA-N 0.000 claims description 5
• IAPCDZHOSMWPKV-UHFFFAOYSA-N 6-fluoro-2-methyl-5-(2-phenylethyl)-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC=CC(F)=C1N2CCC1=CC=CC=C1 IAPCDZHOSMWPKV-UHFFFAOYSA-N 0.000 claims description 5
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• KXXBUVZERIKGCJ-UHFFFAOYSA-N 8-fluoro-2-methyl-5-[2-[4-(trifluoromethyl)phenyl]ethynyl]-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(F)=CC=C1N2C#CC1=CC=C(C(F)(F)F)C=C1 KXXBUVZERIKGCJ-UHFFFAOYSA-N 0.000 claims description 5
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• QIFUPIGOSFZCEZ-UHFFFAOYSA-N 8-fluoro-5-[2-(4-methoxyphenyl)ethynyl]-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1=CC(OC)=CC=C1C#CN1C2=CC=C(F)C=C2C2=C1CCN(C)C2 QIFUPIGOSFZCEZ-UHFFFAOYSA-N 0.000 claims description 5
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• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
• IBUHDDLETPJVGP-UHFFFAOYSA-N 2,8-dimethyl-5-(2-phenylethyl)-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=CC=C1 IBUHDDLETPJVGP-UHFFFAOYSA-N 0.000 claims description 4
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• 125000004076 pyridyl group Chemical group 0.000 claims description 3
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