CA2719412A1 - Pyrido[3,4-b]indoles and methods of use - Google Patents

Info

Publication number

CA2719412A1

CA2719412A1 CA2719412A CA2719412A CA2719412A1 CA 2719412 A1 CA2719412 A1 CA 2719412A1 CA 2719412 A CA2719412 A CA 2719412A CA 2719412 A CA2719412 A CA 2719412A CA 2719412 A1 CA2719412 A1 CA 2719412A1

Authority

CA

Canada

Prior art keywords

substituted

unsubstituted

pyrido

tetrahydro

taken together

Prior art date

2008-03-24

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 36
• AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical class N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 611
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 87
• 208000010877 cognitive disease Diseases 0.000 claims abstract description 41
• 208000028017 Psychotic disease Diseases 0.000 claims abstract description 23
• 230000001537 neural effect Effects 0.000 claims abstract description 23
• 239000002858 neurotransmitter agent Substances 0.000 claims abstract description 23
• 230000001404 mediated effect Effects 0.000 claims abstract description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• -1 perhaloalkyl Chemical group 0.000 claims description 433
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 347
• 125000005843 halogen group Chemical group 0.000 claims description 248
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 220
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 191
• 125000003545 alkoxy group Chemical group 0.000 claims description 185
• 125000000623 heterocyclic group Chemical group 0.000 claims description 166
• 125000003118 aryl group Chemical group 0.000 claims description 157
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 150
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 144
• 150000003839 salts Chemical class 0.000 claims description 139
• 125000001072 heteroaryl group Chemical group 0.000 claims description 134
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 125
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 123
• 125000004442 acylamino group Chemical group 0.000 claims description 118
• 125000005102 carbonylalkoxy group Chemical group 0.000 claims description 106
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 100
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 97
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 96
• 229910052799 carbon Inorganic materials 0.000 claims description 96
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 89
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 89
• 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 86
• 125000004423 acyloxy group Chemical group 0.000 claims description 79
• 125000002252 acyl group Chemical group 0.000 claims description 72
• 125000004001 thioalkyl group Chemical group 0.000 claims description 67
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 63
• 125000004104 aryloxy group Chemical group 0.000 claims description 61
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 60
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 60
• 125000005589 carbonylalkylenealkoxy group Chemical group 0.000 claims description 55
• 150000003573 thiols Chemical class 0.000 claims description 49
• 125000004076 pyridyl group Chemical group 0.000 claims description 48
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 39
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 38
• 125000004432 carbon atom Chemical group C* 0.000 claims description 32
• 125000000304 alkynyl group Chemical group 0.000 claims description 31
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 29
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 25
• 125000005121 aminocarbonylalkoxy group Chemical group 0.000 claims description 23
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 16
• 125000001153 fluoro group Chemical group F* 0.000 claims description 15
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
• 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 10
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
• 125000004193 piperazinyl group Chemical group 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 6
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• 230000001225 therapeutic effect Effects 0.000 abstract description 6
• 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
• AIVGLMHJGRETPC-UHFFFAOYSA-N pyrido[3,4-b]indol-1-one Chemical compound C1=CC=C2C3=CC=NC(=O)C3=NC2=C1 AIVGLMHJGRETPC-UHFFFAOYSA-N 0.000 description 293
• RLFKXSPRHPUPPI-UHFFFAOYSA-N 1h-pyrido[3,4-b]indole Chemical compound C1=CC=C2C3=CC=NCC3=NC2=C1 RLFKXSPRHPUPPI-UHFFFAOYSA-N 0.000 description 158
• 125000000217 alkyl group Chemical group 0.000 description 105
• 239000012453 solvate Substances 0.000 description 72
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 70
• WPJURBQNYWYYLA-UHFFFAOYSA-N 2-pyrido[3,4-b]indol-9-ylacetic acid Chemical compound C1=NC=C2N(CC(=O)O)C3=CC=CC=C3C2=C1 WPJURBQNYWYYLA-UHFFFAOYSA-N 0.000 description 66
• 150000004702 methyl esters Chemical class 0.000 description 55
• WXACQUVKULVAAH-UHFFFAOYSA-N pyrido[3,4-b]indole-9-carboxylic acid Chemical compound C1=NC=C2N(C(=O)O)C3=CC=CC=C3C2=C1 WXACQUVKULVAAH-UHFFFAOYSA-N 0.000 description 55
• 229940075993 receptor modulator Drugs 0.000 description 47
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
• 201000010099 disease Diseases 0.000 description 45
• 125000001424 substituent group Chemical group 0.000 description 36
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 34
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• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 28
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 25
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 25
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• 125000003107 substituted aryl group Chemical group 0.000 description 24
• PVIAUEWEXVRHPE-UHFFFAOYSA-N 2-pyrido[3,4-b]indol-9-ylethanamine Chemical compound C1=NC=C2N(CCN)C3=CC=CC=C3C2=C1 PVIAUEWEXVRHPE-UHFFFAOYSA-N 0.000 description 23
• 230000027455 binding Effects 0.000 description 22
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 22
• 239000000460 chlorine Substances 0.000 description 21
• UEEWDBLGHCZDLR-UHFFFAOYSA-N pyrido[3,4-b]indole-2-carboxylic acid Chemical compound C1=CC=CC2=C3C=CN(C(=O)O)C=C3N=C21 UEEWDBLGHCZDLR-UHFFFAOYSA-N 0.000 description 21
• 239000000203 mixture Substances 0.000 description 20
• 208000024827 Alzheimer disease Diseases 0.000 description 19
• 229910052739 hydrogen Inorganic materials 0.000 description 19
• 125000001624 naphthyl group Chemical group 0.000 description 19
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 18
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 18
• 230000000875 corresponding effect Effects 0.000 description 17
• WJEPOYQHMOODJY-UHFFFAOYSA-N 1h-pyrido[3,4-b]indole-2,9-dicarboxylic acid Chemical compound C12=CC=CC=C2N(C(O)=O)C2=C1C=CN(C(=O)O)C2 WJEPOYQHMOODJY-UHFFFAOYSA-N 0.000 description 16
• 125000003342 alkenyl group Chemical group 0.000 description 16
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 16
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• 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 10
• 208000014674 injury Diseases 0.000 description 10
• JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 description 10
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• SEOWACAFBQXTCN-UHFFFAOYSA-N 2-pyrido[3,4-b]indol-9-ylacetamide Chemical compound C1=NC=C2N(CC(=O)N)C3=CC=CC=C3C2=C1 SEOWACAFBQXTCN-UHFFFAOYSA-N 0.000 description 9
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