MX2012010292A - Inhibidores de amina oxidasa sensible a semicarbazida. - Google Patents

Info

Publication number

MX2012010292A

MX2012010292A MX2012010292A MX2012010292A MX2012010292A MX 2012010292 A MX2012010292 A MX 2012010292A MX 2012010292 A MX2012010292 A MX 2012010292A MX 2012010292 A MX2012010292 A MX 2012010292A MX 2012010292 A MX2012010292 A MX 2012010292A

Authority

MX

Mexico

Prior art keywords

alkyl

mmol

compound according

pyridin

amino

Prior art date

2010-03-15

Links

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• 239000003112 inhibitor Substances 0.000 title abstract description 13
• 108090000854 Oxidoreductases Proteins 0.000 title description 6
• 102000004316 Oxidoreductases Human genes 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 268
• -1 cyano, amino, hydroxyl Chemical group 0.000 claims description 215
• 125000000217 alkyl group Chemical group 0.000 claims description 146
• 238000000034 method Methods 0.000 claims description 86
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 73
• 239000000203 mixture Substances 0.000 claims description 53
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• 229920006395 saturated elastomer Polymers 0.000 claims description 35
• 239000001257 hydrogen Substances 0.000 claims description 34
• 125000003545 alkoxy group Chemical group 0.000 claims description 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 26
• 125000001424 substituent group Chemical group 0.000 claims description 26
• 238000011282 treatment Methods 0.000 claims description 25
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
• 239000011737 fluorine Substances 0.000 claims description 21
• 229910052731 fluorine Inorganic materials 0.000 claims description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 20
• 201000010099 disease Diseases 0.000 claims description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims description 19
• 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 18
• 239000000460 chlorine Substances 0.000 claims description 17
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 16
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
• 229910052736 halogen Inorganic materials 0.000 claims description 16
• 150000002367 halogens Chemical class 0.000 claims description 16
• 229910052757 nitrogen Inorganic materials 0.000 claims description 16
• 150000003839 salts Chemical class 0.000 claims description 16
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 15
• 230000005764 inhibitory process Effects 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
• 229910052801 chlorine Inorganic materials 0.000 claims description 13
• 125000003282 alkyl amino group Chemical group 0.000 claims description 12
• 125000003277 amino group Chemical group 0.000 claims description 12
• 230000004054 inflammatory process Effects 0.000 claims description 12
• 206010061218 Inflammation Diseases 0.000 claims description 11
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
• 208000027866 inflammatory disease Diseases 0.000 claims description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 10
• 125000002757 morpholinyl group Chemical group 0.000 claims description 9
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
• 125000004193 piperazinyl group Chemical group 0.000 claims description 9
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 9
• 125000003386 piperidinyl group Chemical group 0.000 claims description 9
• 125000002947 alkylene group Chemical group 0.000 claims description 8
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• 150000001204 N-oxides Chemical class 0.000 claims description 7
• 125000001188 haloalkyl group Chemical group 0.000 claims description 7
• 230000002757 inflammatory effect Effects 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 7
• 230000004614 tumor growth Effects 0.000 claims description 7
• 208000023275 Autoimmune disease Diseases 0.000 claims description 6
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
• 125000004122 cyclic group Chemical group 0.000 claims description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
• 150000003254 radicals Chemical class 0.000 claims description 6
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
• 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 5
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
• 125000002950 monocyclic group Chemical group 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 5
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• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
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• 206010012438 Dermatitis atopic Diseases 0.000 claims description 4
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
• 206010047115 Vasculitis Diseases 0.000 claims description 4
• 201000008937 atopic dermatitis Diseases 0.000 claims description 4
• 125000000068 chlorophenyl group Chemical group 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
• 125000004043 oxo group Chemical group O=* 0.000 claims description 4
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
• 239000005977 Ethylene Substances 0.000 claims description 3
• 206010019280 Heart failures Diseases 0.000 claims description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
• 206010003246 arthritis Diseases 0.000 claims description 3
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 206010012601 diabetes mellitus Diseases 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 3
• 201000006417 multiple sclerosis Diseases 0.000 claims description 3
• IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims description 3
• 125000000565 sulfonamide group Chemical group 0.000 claims description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• VPNRBAOCCZTCJQ-UHFFFAOYSA-N 4-[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]morpholine Chemical compound C1=CC(Cl)=CC=C1N1C2=CN=CC=C2C(N2CCOCC2)=C1 VPNRBAOCCZTCJQ-UHFFFAOYSA-N 0.000 claims description 2
• 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 description 2
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
• SZBGXBOFCGNPEU-UHFFFAOYSA-N 5-aminopentanal Chemical compound NCCCCC=O SZBGXBOFCGNPEU-UHFFFAOYSA-N 0.000 claims description 2
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
• POOPWPIOIMBTOH-UHFFFAOYSA-N 8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1O2 POOPWPIOIMBTOH-UHFFFAOYSA-N 0.000 claims description 2
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
• 208000022309 Alcoholic Liver disease Diseases 0.000 claims description 2
• 201000001320 Atherosclerosis Diseases 0.000 claims description 2
• 206010003827 Autoimmune hepatitis Diseases 0.000 claims description 2
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 2
• 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 2
• 206010007558 Cardiac failure chronic Diseases 0.000 claims description 2
• 206010008609 Cholangitis sclerosing Diseases 0.000 claims description 2
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
• 208000011231 Crohn disease Diseases 0.000 claims description 2
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
• 208000019693 Lung disease Diseases 0.000 claims description 2
• 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 2
• 201000004681 Psoriasis Diseases 0.000 claims description 2
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• 206010063837 Reperfusion injury Diseases 0.000 claims description 2
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• 206010039710 Scleroderma Diseases 0.000 claims description 2
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• 201000009594 Systemic Scleroderma Diseases 0.000 claims description 2
• 206010042953 Systemic sclerosis Diseases 0.000 claims description 2
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• 230000001363 autoimmune Effects 0.000 claims description 2
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• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
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• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
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• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
• 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 claims description 2
• 208000010125 myocardial infarction Diseases 0.000 claims description 2
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• JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims description 2
• 208000010157 sclerosing cholangitis Diseases 0.000 claims description 2
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• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 2
• 150000002431 hydrogen Chemical group 0.000 claims 7
• ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical group C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 claims 2
• SMUBIDCJYGLKLB-UHFFFAOYSA-N 3-[1-(4-methylphenyl)pyrazolo[3,4-c]pyridin-3-yl]-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1=CC(C)=CC=C1N1C2=CN=CC=C2C(N2CC3CCC(O3)C2)=N1 SMUBIDCJYGLKLB-UHFFFAOYSA-N 0.000 claims 1
• DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 claims 1
• LJIUNHRAINKSRB-UHFFFAOYSA-N 4-[1-(4-methylphenyl)pyrazolo[3,4-c]pyridin-3-yl]piperazin-2-one Chemical compound C1=CC(C)=CC=C1N1C2=CN=CC=C2C(N2CC(=O)NCC2)=N1 LJIUNHRAINKSRB-UHFFFAOYSA-N 0.000 claims 1
• BJWKMIUJDVPMLT-UHFFFAOYSA-N ClC1=CC=C(C=C1)C1=NC(=C2N1C=CN=C2)C2CCOCC2.ClC2=CC=C(C=C2)C2=NC(=C1N2C=CN=C1)N1CCOCC1.CC1=CC=C(C=C1)C1=NC(=C2N1C=CN=C2)N2CCOCC2 Chemical compound ClC1=CC=C(C=C1)C1=NC(=C2N1C=CN=C2)C2CCOCC2.ClC2=CC=C(C=C2)C2=NC(=C1N2C=CN=C1)N1CCOCC1.CC1=CC=C(C=C1)C1=NC(=C2N1C=CN=C2)N2CCOCC2 BJWKMIUJDVPMLT-UHFFFAOYSA-N 0.000 claims 1
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• STBUWXYTSVWZIS-UHFFFAOYSA-N morpholine;2,2,2-trifluoroacetic acid Chemical compound C1COCCN1.OC(=O)C(F)(F)F STBUWXYTSVWZIS-UHFFFAOYSA-N 0.000 claims 1
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• 239000000243 solution Substances 0.000 description 42
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