SA07280361B1 - مشتقات ازا إندول مع توليفة من مساعد مستقبل اسيتيل كولين نيكوتيني جزئي و مثبط إعادة امتصاص الدوبامين - Google Patents

Info

Publication number

SA07280361B1

SA07280361B1 SA07280361A SA07280361A SA07280361B1 SA 07280361 B1 SA07280361 B1 SA 07280361B1 SA 07280361 A SA07280361 A SA 07280361A SA 07280361 A SA07280361 A SA 07280361A SA 07280361 B1 SA07280361 B1 SA 07280361B1

Authority

SA

Saudi Arabia

Prior art keywords

pyrrolo

pyridine

pyrrolidin

compound

ylmethyl

Prior art date

2006-07-06

Links

• Espacenet
• Global Dossier
• Discuss

• 125000005334 azaindolyl group Chemical class N1N=C(C2=CC=CC=C12)* 0.000 title claims abstract description 6
• 230000005764 inhibitory process Effects 0.000 title abstract description 11
• 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 title abstract description 10
• 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 title abstract description 10
• 230000002825 dopamine reuptake Effects 0.000 title abstract description 9
• 230000036961 partial effect Effects 0.000 title abstract description 7
• 230000008484 agonism Effects 0.000 title abstract description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 322
• 238000000034 method Methods 0.000 claims abstract description 72
• 238000003786 synthesis reaction Methods 0.000 claims abstract description 27
• 230000015572 biosynthetic process Effects 0.000 claims abstract description 26
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
• -1 1,2,3,6-tetrahydropyridin-4-yl Chemical group 0.000 claims description 46
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 45
• 208000035475 disorder Diseases 0.000 claims description 40
• 150000003839 salts Chemical class 0.000 claims description 35
• 125000000217 alkyl group Chemical group 0.000 claims description 30
• 239000003814 drug Substances 0.000 claims description 26
• 238000011282 treatment Methods 0.000 claims description 22
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
• 150000002367 halogens Chemical class 0.000 claims description 20
• 229910052736 halogen Inorganic materials 0.000 claims description 19
• 229910052739 hydrogen Inorganic materials 0.000 claims description 17
• 239000004480 active ingredient Substances 0.000 claims description 15
• 239000001257 hydrogen Substances 0.000 claims description 14
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
• 206010013663 drug dependence Diseases 0.000 claims description 12
• 125000000304 alkynyl group Chemical group 0.000 claims description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
• MVXVYAKCVDQRLW-UHFFFAOYSA-N azain Natural products C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 claims description 10
• 229910052757 nitrogen Inorganic materials 0.000 claims description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
• 125000003545 alkoxy group Chemical group 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• 125000001424 substituent group Chemical group 0.000 claims description 9
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• 208000022497 Cocaine-Related disease Diseases 0.000 claims description 8
• 206010012335 Dependence Diseases 0.000 claims description 8
• 206010057852 Nicotine dependence Diseases 0.000 claims description 8
• 208000025569 Tobacco Use disease Diseases 0.000 claims description 8
• 201000006145 cocaine dependence Diseases 0.000 claims description 8
• 238000002360 preparation method Methods 0.000 claims description 8
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 8
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 7
• 125000003725 azepanyl group Chemical group 0.000 claims description 7
• 230000004054 inflammatory process Effects 0.000 claims description 7
• 125000002757 morpholinyl group Chemical group 0.000 claims description 7
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
• 125000003386 piperidinyl group Chemical group 0.000 claims description 7
• 238000006467 substitution reaction Methods 0.000 claims description 7
• HZOQVOGSPNJBDJ-UHFFFAOYSA-N 6-chloro-3-piperidin-3-yl-1h-pyrrolo[2,3-b]pyridine Chemical compound C=1NC2=NC(Cl)=CC=C2C=1C1CCCNC1 HZOQVOGSPNJBDJ-UHFFFAOYSA-N 0.000 claims description 6
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 6
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 6
• 150000001204 N-oxides Chemical class 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 6
• 201000011510 cancer Diseases 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• 201000000980 schizophrenia Diseases 0.000 claims description 6
• HQXXEVXSXRYNIL-UHFFFAOYSA-N 2-piperidin-3-yl-1h-pyrrolo[2,3-b]pyridine Chemical compound C1CCNCC1C1=CC2=CC=CN=C2N1 HQXXEVXSXRYNIL-UHFFFAOYSA-N 0.000 claims description 5
• NUZPLGPQBGJPBA-UHFFFAOYSA-N 2-pyrrolidin-3-yl-1h-pyrrolo[3,2-b]pyridine Chemical compound C1NCCC1C1=CC2=NC=CC=C2N1 NUZPLGPQBGJPBA-UHFFFAOYSA-N 0.000 claims description 5
• 208000024827 Alzheimer disease Diseases 0.000 claims description 5
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• 208000010412 Glaucoma Diseases 0.000 claims description 5
• 239000002671 adjuvant Substances 0.000 claims description 5
• 125000004429 atom Chemical group 0.000 claims description 5
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 235000014632 disordered eating Nutrition 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 208000002780 macular degeneration Diseases 0.000 claims description 5
• 125000006239 protecting group Chemical group 0.000 claims description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
• 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
• 208000002193 Pain Diseases 0.000 claims description 4
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 230000000926 neurological effect Effects 0.000 claims description 4
• 230000001681 protective effect Effects 0.000 claims description 4
• QPUBXZPBYMJDEG-UHFFFAOYSA-N 2-(pyrrolidin-3-ylmethyl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C=1C2=CC=CN=C2NC=1CC1CCNC1 QPUBXZPBYMJDEG-UHFFFAOYSA-N 0.000 claims description 3
• KOWVUSHBSAGCKE-UHFFFAOYSA-N 2-pyrrolidin-3-yl-1h-pyrrolo[2,3-b]pyridine Chemical compound C1NCCC1C1=CC2=CC=CN=C2N1 KOWVUSHBSAGCKE-UHFFFAOYSA-N 0.000 claims description 3
• DXGJKCSUCOWWHS-SNVBAGLBSA-N 3-[[(2r)-pyrrolidin-2-yl]methyl]-1h-pyrrolo[3,2-b]pyridine Chemical compound C=1NC2=CC=CN=C2C=1C[C@H]1CCCN1 DXGJKCSUCOWWHS-SNVBAGLBSA-N 0.000 claims description 3
• NDEZQKHXMUBWSL-UHFFFAOYSA-N 3-piperidin-3-yl-1h-pyrrolo[2,3-b]pyridine Chemical compound C1CCNCC1C1=CNC2=NC=CC=C12 NDEZQKHXMUBWSL-UHFFFAOYSA-N 0.000 claims description 3
• DMSFDSUCMFEQSB-UHFFFAOYSA-N 6-chloro-2-piperidin-3-yl-1h-pyrrolo[2,3-b]pyridine Chemical compound N1C2=NC(Cl)=CC=C2C=C1C1CCCNC1 DMSFDSUCMFEQSB-UHFFFAOYSA-N 0.000 claims description 3
• 208000029197 Amphetamine-Related disease Diseases 0.000 claims description 3
• 208000008238 Muscle Spasticity Diseases 0.000 claims description 3
• 208000022873 Ocular disease Diseases 0.000 claims description 3
• 230000036506 anxiety Effects 0.000 claims description 3
• 208000015114 central nervous system disease Diseases 0.000 claims description 3
• 125000005429 oxyalkyl group Chemical group 0.000 claims description 3
• 208000018198 spasticity Diseases 0.000 claims description 3
• SDGPEULKVVRCDT-UHFFFAOYSA-N 2-[(1-methylpyrrolidin-3-yl)methyl]-1h-pyrrolo[2,3-b]pyridine Chemical compound C1N(C)CCC1CC1=CC2=CC=CN=C2N1 SDGPEULKVVRCDT-UHFFFAOYSA-N 0.000 claims description 2
• IUWFNLKNENWKCN-GFCCVEGCSA-N 2-[[(2r)-1-methylpyrrolidin-2-yl]methyl]-1h-pyrrolo[2,3-b]pyridine Chemical compound CN1CCC[C@@H]1CC1=CC2=CC=CN=C2N1 IUWFNLKNENWKCN-GFCCVEGCSA-N 0.000 claims description 2
• MVQHAOQHZJARGP-SNVBAGLBSA-N 2-[[(2r)-pyrrolidin-2-yl]methyl]-1h-pyrrolo[2,3-b]pyridine Chemical compound C=1C2=CC=CN=C2NC=1C[C@H]1CCCN1 MVQHAOQHZJARGP-SNVBAGLBSA-N 0.000 claims description 2
• LXKWIYXGQRBTMJ-UHFFFAOYSA-N 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)piperidin-3-ol Chemical compound C=1C2=CC=CN=C2NC=1C1(O)CCCNC1 LXKWIYXGQRBTMJ-UHFFFAOYSA-N 0.000 claims description 2
• JWRMVSAPVLYMID-SNVBAGLBSA-N 6-methoxy-2-[[(2r)-pyrrolidin-2-yl]methyl]-1h-pyrrolo[2,3-b]pyridine Chemical compound N1C2=NC(OC)=CC=C2C=C1C[C@H]1CCCN1 JWRMVSAPVLYMID-SNVBAGLBSA-N 0.000 claims description 2
• 125000001309 chloro group Chemical group Cl* 0.000 claims 8
• 125000002346 iodo group Chemical group I* 0.000 claims 7
• 125000001246 bromo group Chemical group Br* 0.000 claims 6
• 125000001153 fluoro group Chemical group F* 0.000 claims 6
• TXPYXAKYINORQW-UHFFFAOYSA-N 2-(1,2,3,6-tetrahydropyridin-5-yl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1NCCC=C1C1=CC2=CC=CN=C2N1 TXPYXAKYINORQW-UHFFFAOYSA-N 0.000 claims 1
• ZGAVHNKXQWQBES-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC(C3C4CCN(C3)CC4)=CC2=C1 ZGAVHNKXQWQBES-UHFFFAOYSA-N 0.000 claims 1
• MVQHAOQHZJARGP-UHFFFAOYSA-N 2-(pyrrolidin-2-ylmethyl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C=1C2=CC=CN=C2NC=1CC1CCCN1 MVQHAOQHZJARGP-UHFFFAOYSA-N 0.000 claims 1
• BFUIPMNVERZGCT-UHFFFAOYSA-N 2-[(1-benzylpyrrolidin-3-yl)methyl]-1h-pyrrolo[2,3-b]pyridine Chemical compound C=1C2=CC=CN=C2NC=1CC(C1)CCN1CC1=CC=CC=C1 BFUIPMNVERZGCT-UHFFFAOYSA-N 0.000 claims 1
• HQXXEVXSXRYNIL-SNVBAGLBSA-N 2-[(3r)-piperidin-3-yl]-1h-pyrrolo[2,3-b]pyridine Chemical compound C1CCNC[C@@H]1C1=CC2=CC=CN=C2N1 HQXXEVXSXRYNIL-SNVBAGLBSA-N 0.000 claims 1
• HQXXEVXSXRYNIL-JTQLQIEISA-N 2-[(3s)-piperidin-3-yl]-1h-pyrrolo[2,3-b]pyridine Chemical compound C1CCNC[C@H]1C1=CC2=CC=CN=C2N1 HQXXEVXSXRYNIL-JTQLQIEISA-N 0.000 claims 1
• KOWVUSHBSAGCKE-VIFPVBQESA-N 2-[(3s)-pyrrolidin-3-yl]-1h-pyrrolo[2,3-b]pyridine Chemical compound C1NCC[C@@H]1C1=CC2=CC=CN=C2N1 KOWVUSHBSAGCKE-VIFPVBQESA-N 0.000 claims 1
• NPLJNUAVAWGZGR-UHFFFAOYSA-N 3-(1-azabicyclo[2.2.2]octan-3-yl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CC=C2C(C3C4CCN(C3)CC4)=CNC2=N1 NPLJNUAVAWGZGR-UHFFFAOYSA-N 0.000 claims 1
• SHGMBMJNLCDVRS-UHFFFAOYSA-N 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1=CN=C2NC(C3(C4CCN(CC4)C3)O)=CC2=C1 SHGMBMJNLCDVRS-UHFFFAOYSA-N 0.000 claims 1
• OXHZNTMCRRNPNU-UHFFFAOYSA-N C=1NC=2[N+]([O-])=CC=CC=2C=1C1CCCNC1 Chemical compound C=1NC=2[N+]([O-])=CC=CC=2C=1C1CCCNC1 OXHZNTMCRRNPNU-UHFFFAOYSA-N 0.000 claims 1
• GBUAEHSSPCXBSL-UHFFFAOYSA-N N1C=2[N+]([O-])=CC=CC=2C=C1C1CCCNC1 Chemical compound N1C=2[N+]([O-])=CC=CC=2C=C1C1CCCNC1 GBUAEHSSPCXBSL-UHFFFAOYSA-N 0.000 claims 1
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• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
• 125000005322 morpholin-1-yl group Chemical group 0.000 claims 1
• 230000000955 neuroendocrine Effects 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 116
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• 239000000243 solution Substances 0.000 description 71
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