MX2008011791A - Azaciclilaminas-n-sustituidas como antagonistas de histamina-3. - Google Patents

Info

Publication number

MX2008011791A

MX2008011791A MX2008011791A MX2008011791A MX2008011791A MX 2008011791 A MX2008011791 A MX 2008011791A MX 2008011791 A MX2008011791 A MX 2008011791A MX 2008011791 A MX2008011791 A MX 2008011791A MX 2008011791 A MX2008011791 A MX 2008011791A

Authority

MX

Mexico

Prior art keywords

methyl

benzoyl

benzimidazol

bipyrrolidine

pyrrolidin

Prior art date

2006-03-15

Links

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• 150000001875 compounds Chemical class 0.000 claims abstract description 143
• 238000011282 treatment Methods 0.000 claims abstract description 24
• 208000015114 central nervous system disease Diseases 0.000 claims abstract description 9
• 208000012902 Nervous system disease Diseases 0.000 claims abstract description 3
• -1 cycloheteroalkyl Chemical group 0.000 claims description 260
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 113
• 229910052757 nitrogen Inorganic materials 0.000 claims description 73
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 72
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 58
• 238000000034 method Methods 0.000 claims description 58
• 238000002360 preparation method Methods 0.000 claims description 48
• 150000003839 salts Chemical class 0.000 claims description 23
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• 102000004384 Histamine H3 receptors Human genes 0.000 claims description 16
• 108090000981 Histamine H3 receptors Proteins 0.000 claims description 16
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
• 239000002904 solvent Substances 0.000 claims description 15
• 125000003118 aryl group Chemical group 0.000 claims description 14
• 125000004429 atom Chemical group 0.000 claims description 14
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• NGXSWUFDCSEIOO-UHFFFAOYSA-N pyrrolidin-3-amine Chemical compound NC1CCNC1 NGXSWUFDCSEIOO-UHFFFAOYSA-N 0.000 claims description 14
• 208000024827 Alzheimer disease Diseases 0.000 claims description 12
• 150000001412 amines Chemical class 0.000 claims description 12
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 12
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
• 125000001072 heteroaryl group Chemical group 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
• 208000010877 cognitive disease Diseases 0.000 claims description 9
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• 102000005962 receptors Human genes 0.000 claims description 9
• 108020003175 receptors Proteins 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• 125000002619 bicyclic group Chemical group 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• XKLNOVWDVMWTOB-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1h-carbazole Chemical compound N1C2=CC=CC=C2C2=C1CCCC2 XKLNOVWDVMWTOB-UHFFFAOYSA-N 0.000 claims description 6
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 6
• 125000003342 alkenyl group Chemical group 0.000 claims description 6
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 150000002367 halogens Chemical class 0.000 claims description 6
• 201000000980 schizophrenia Diseases 0.000 claims description 6
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 5
• 125000004122 cyclic group Chemical group 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
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• 230000008569 process Effects 0.000 claims description 5
• 208000019116 sleep disease Diseases 0.000 claims description 5
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 4
• ZZCKGXAYSCVENO-UHFFFAOYSA-N 1-[[4-[(4-fluorobenzimidazol-1-yl)methyl]phenyl]methyl]-n,n-dimethylpyrrolidin-3-amine Chemical compound C1C(N(C)C)CCN1CC(C=C1)=CC=C1CN1C2=CC=CC(F)=C2N=C1 ZZCKGXAYSCVENO-UHFFFAOYSA-N 0.000 claims description 3
• 150000001556 benzimidazoles Chemical group 0.000 claims description 3
• WNYFCVHBWNPGFS-UHFFFAOYSA-N 1-[[2-chloro-4-[(3-piperidin-1-ylpyrrolidin-1-yl)methyl]phenyl]methyl]benzimidazole Chemical compound C=1C=C(CN2C3=CC=CC=C3N=C2)C(Cl)=CC=1CN(C1)CCC1N1CCCCC1 WNYFCVHBWNPGFS-UHFFFAOYSA-N 0.000 claims description 2
• OAATWPVYGXYKIX-UHFFFAOYSA-N 1-[[2-chloro-4-[(3-pyrrolidin-1-ylpyrrolidin-1-yl)methyl]phenyl]methyl]benzimidazole Chemical compound C=1C=C(CN2C3=CC=CC=C3N=C2)C(Cl)=CC=1CN(C1)CCC1N1CCCC1 OAATWPVYGXYKIX-UHFFFAOYSA-N 0.000 claims description 2
• FSCHBUFEORTTSK-UHFFFAOYSA-N 1-[[4-(benzimidazol-1-ylmethyl)-3-chlorophenyl]methyl]-n,n-dimethylpyrrolidin-3-amine Chemical compound C1C(N(C)C)CCN1CC(C=C1Cl)=CC=C1CN1C2=CC=CC=C2N=C1 FSCHBUFEORTTSK-UHFFFAOYSA-N 0.000 claims description 2
• XIKKJGSHMQMXPV-UHFFFAOYSA-N 1-[[4-(benzimidazol-1-ylmethyl)-3-chlorophenyl]methyl]-n-ethyl-n-methylpyrrolidin-3-amine Chemical compound C1C(N(C)CC)CCN1CC(C=C1Cl)=CC=C1CN1C2=CC=CC=C2N=C1 XIKKJGSHMQMXPV-UHFFFAOYSA-N 0.000 claims description 2
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
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• LPTXIOWQQHYDOK-UHFFFAOYSA-N [3-(azepan-1-yl)pyrrolidin-1-yl]-[4-[(5-methylbenzimidazol-1-yl)methyl]phenyl]methanone Chemical compound C1=NC2=CC(C)=CC=C2N1CC(C=C1)=CC=C1C(=O)N(C1)CCC1N1CCCCCC1 LPTXIOWQQHYDOK-UHFFFAOYSA-N 0.000 claims description 2
• RHHNYZPUWAFSQK-NRFANRHFSA-N [4-(1h-indol-3-ylmethyl)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound N1([C@H]2CCN(C2)C(=O)C=2C=CC(CC=3C4=CC=CC=C4NC=3)=CC=2)CCCC1 RHHNYZPUWAFSQK-NRFANRHFSA-N 0.000 claims description 2
• MKFUTLJBZBYCCA-UHFFFAOYSA-N [4-(benzimidazol-1-ylmethyl)-2-fluorophenyl]-(3-pyrrolidin-1-ylpyrrolidin-1-yl)methanone Chemical compound FC1=CC(CN2C3=CC=CC=C3N=C2)=CC=C1C(=O)N(C1)CCC1N1CCCC1 MKFUTLJBZBYCCA-UHFFFAOYSA-N 0.000 claims description 2
• FLFNHBOROKVAFC-UHFFFAOYSA-N [4-(benzimidazol-1-ylmethyl)phenyl]-(3-piperidin-1-ylpiperidin-1-yl)methanone Chemical compound C=1C=C(CN2C3=CC=CC=C3N=C2)C=CC=1C(=O)N(C1)CCCC1N1CCCCC1 FLFNHBOROKVAFC-UHFFFAOYSA-N 0.000 claims description 2
• YOPCFDOLUZCVKR-UHFFFAOYSA-N [4-(benzimidazol-1-ylmethyl)phenyl]-[3-(4-methylpiperidin-1-yl)pyrrolidin-1-yl]methanone Chemical compound C1CC(C)CCN1C1CN(C(=O)C=2C=CC(CN3C4=CC=CC=C4N=C3)=CC=2)CC1 YOPCFDOLUZCVKR-UHFFFAOYSA-N 0.000 claims description 2
• IENOVDDWBKZXOA-UHFFFAOYSA-N [4-[(5-methylbenzimidazol-1-yl)methyl]phenyl]-[3-(4-methylpiperidin-1-yl)pyrrolidin-1-yl]methanone Chemical compound C1CC(C)CCN1C1CN(C(=O)C=2C=CC(CN3C4=CC=C(C)C=C4N=C3)=CC=2)CC1 IENOVDDWBKZXOA-UHFFFAOYSA-N 0.000 claims description 2
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 2
• 208000020685 sleep-wake disease Diseases 0.000 claims description 2
• NKJNVVMJEBRTDJ-NRFANRHFSA-N (4-benzylphenyl)-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound N1([C@H]2CCN(C2)C(=O)C=2C=CC(CC=3C=CC=CC=3)=CC=2)CCCC1 NKJNVVMJEBRTDJ-NRFANRHFSA-N 0.000 claims 1
• GLKFHNCBBKKHGM-UHFFFAOYSA-N 1-(2-phenylethyl)benzimidazole Chemical compound C1=NC2=CC=CC=C2N1CCC1=CC=CC=C1 GLKFHNCBBKKHGM-UHFFFAOYSA-N 0.000 claims 1
• XNEFBIXQNVFRLQ-WIIYFNMSSA-N 1-[1-[4-[(3s)-3-pyrrolidin-1-ylpyrrolidine-1-carbonyl]phenyl]ethyl]indole-5-carbonitrile Chemical compound N1([C@H]2CCN(C2)C(=O)C2=CC=C(C=C2)C(C)N2C3=CC=C(C=C3C=C2)C#N)CCCC1 XNEFBIXQNVFRLQ-WIIYFNMSSA-N 0.000 claims 1
• ULCMJQLTPQGROK-UHFFFAOYSA-N 1-[[4-[(5-fluorobenzimidazol-1-yl)methyl]phenyl]methyl]-n,n-dimethylpyrrolidin-3-amine Chemical compound C1C(N(C)C)CCN1CC(C=C1)=CC=C1CN1C2=CC=C(F)C=C2N=C1 ULCMJQLTPQGROK-UHFFFAOYSA-N 0.000 claims 1
• QWRDXHCEAZUHDY-UHFFFAOYSA-N 1-[[4-[(6-fluorobenzimidazol-1-yl)methyl]phenyl]methyl]-n,n-dimethylpyrrolidin-3-amine Chemical compound C1C(N(C)C)CCN1CC(C=C1)=CC=C1CN1C2=CC(F)=CC=C2N=C1 QWRDXHCEAZUHDY-UHFFFAOYSA-N 0.000 claims 1
• HFZLSTDPRQSZCQ-UHFFFAOYSA-N 1-pyrrolidin-3-ylpyrrolidine Chemical compound C1CCCN1C1CNCC1 HFZLSTDPRQSZCQ-UHFFFAOYSA-N 0.000 claims 1
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
• 208000020358 Learning disease Diseases 0.000 claims 1
• YFOVYMUNACKLJM-SFHVURJKSA-N [(3s)-3-(azetidin-1-yl)pyrrolidin-1-yl]-[4-[(7-fluorobenzimidazol-1-yl)methyl]phenyl]methanone Chemical compound N1([C@H]2CCN(C2)C(=O)C2=CC=C(C=C2)CN2C=NC=3C=CC=C(C2=3)F)CCC1 YFOVYMUNACKLJM-SFHVURJKSA-N 0.000 claims 1
• YHKWENOEKQIQIK-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-(indol-1-ylmethyl)phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1CN1C2=CC=CC=C2C=C1 YHKWENOEKQIQIK-UHFFFAOYSA-N 0.000 claims 1
• HCASEGGSGZPNRG-UHFFFAOYSA-N [4-(1h-benzimidazol-2-ylmethyl)phenyl]-(3-pyrrolidin-1-ylpyrrolidin-1-yl)methanone Chemical compound C=1C=C(CC=2NC3=CC=CC=C3N=2)C=CC=1C(=O)N(C1)CCC1N1CCCC1 HCASEGGSGZPNRG-UHFFFAOYSA-N 0.000 claims 1
• WMGFFKHQNCLGHB-WIYYLYMNSA-N [4-(benzimidazol-1-ylmethyl)phenyl]-[(3r)-3-[(2r)-2-methylpyrrolidin-1-yl]pyrrolidin-1-yl]methanone Chemical compound C[C@@H]1CCCN1[C@H]1CN(C(=O)C=2C=CC(CN3C4=CC=CC=C4N=C3)=CC=2)CC1 WMGFFKHQNCLGHB-WIYYLYMNSA-N 0.000 claims 1
• WMGFFKHQNCLGHB-GHTZIAJQSA-N [4-(benzimidazol-1-ylmethyl)phenyl]-[(3r)-3-[(2s)-2-methylpyrrolidin-1-yl]pyrrolidin-1-yl]methanone Chemical compound C[C@H]1CCCN1[C@H]1CN(C(=O)C=2C=CC(CN3C4=CC=CC=C4N=C3)=CC=2)CC1 WMGFFKHQNCLGHB-GHTZIAJQSA-N 0.000 claims 1
• RBFNAMZWICIZDO-UHFFFAOYSA-N [4-(benzimidazol-1-ylmethyl)phenyl]-[3-(2-methylpyrrolidin-1-yl)piperidin-1-yl]methanone Chemical compound CC1CCCN1C1CN(C(=O)C=2C=CC(CN3C4=CC=CC=C4N=C3)=CC=2)CCC1 RBFNAMZWICIZDO-UHFFFAOYSA-N 0.000 claims 1
• QMGPOQDFYWLZBM-UHFFFAOYSA-N [4-[(5-methylbenzimidazol-1-yl)methyl]phenyl]-(3-piperidin-1-ylpyrrolidin-1-yl)methanone Chemical compound C1=NC2=CC(C)=CC=C2N1CC(C=C1)=CC=C1C(=O)N(C1)CCC1N1CCCCC1 QMGPOQDFYWLZBM-UHFFFAOYSA-N 0.000 claims 1
• AWEAEUZMHXHUEQ-UHFFFAOYSA-N [4-[(5-methylbenzimidazol-1-yl)methyl]phenyl]-(3-pyrrolidin-1-ylpyrrolidin-1-yl)methanone Chemical compound C1=NC2=CC(C)=CC=C2N1CC(C=C1)=CC=C1C(=O)N(C1)CCC1N1CCCC1 AWEAEUZMHXHUEQ-UHFFFAOYSA-N 0.000 claims 1
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• NTPRGPLMLQUNES-FQEVSTJZSA-N [4-[(7-fluorobenzimidazol-1-yl)methyl]phenyl]-[(3s)-3-piperidin-1-ylpyrrolidin-1-yl]methanone Chemical compound N1([C@H]2CCN(C2)C(=O)C2=CC=C(C=C2)CN2C=NC=3C=CC=C(C2=3)F)CCCCC1 NTPRGPLMLQUNES-FQEVSTJZSA-N 0.000 claims 1
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• OMPPJJVKMXILOM-UHFFFAOYSA-N n,n-dimethyl-1-[[4-[(6-methylbenzimidazol-1-yl)methyl]phenyl]methyl]pyrrolidin-3-amine Chemical compound C1C(N(C)C)CCN1CC(C=C1)=CC=C1CN1C2=CC(C)=CC=C2N=C1 OMPPJJVKMXILOM-UHFFFAOYSA-N 0.000 claims 1
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