HRP20050926A2 - Beta-carbolines useful for treating inflammatory disease - Google Patents

Info

Publication number

HRP20050926A2

HRP20050926A2 HR20050926A HRP20050926A HRP20050926A2 HR P20050926 A2 HRP20050926 A2 HR P20050926A2 HR 20050926 A HR20050926 A HR 20050926A HR P20050926 A HRP20050926 A HR P20050926A HR P20050926 A2 HRP20050926 A2 HR P20050926A2

Authority

HR

Croatia

Prior art keywords

hydrogen

aliphatic

halogen

amino

independently selected

Prior art date

2003-04-09

Links

• Espacenet
• Global Dossier
• Discuss

• AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical class N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 title claims abstract description 18
• 208000027866 inflammatory disease Diseases 0.000 title claims abstract description 15
• 150000001875 compounds Chemical class 0.000 claims abstract description 189
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 43
• 201000010099 disease Diseases 0.000 claims abstract description 26
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 14
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 8
• 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 7
• 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 7
• 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 7
• 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 abstract description 5
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims abstract description 5
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 5
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 5
• 238000000034 method Methods 0.000 claims description 165
• 239000001257 hydrogen Substances 0.000 claims description 149
• 229910052739 hydrogen Inorganic materials 0.000 claims description 149
• 125000001931 aliphatic group Chemical group 0.000 claims description 146
• -1 hydroxy, amino Chemical group 0.000 claims description 115
• 239000000203 mixture Substances 0.000 claims description 113
• 201000006417 multiple sclerosis Diseases 0.000 claims description 86
• 229910052736 halogen Inorganic materials 0.000 claims description 85
• 150000002367 halogens Chemical class 0.000 claims description 85
• 150000002431 hydrogen Chemical class 0.000 claims description 70
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 58
• 125000000623 heterocyclic group Chemical group 0.000 claims description 56
• 229910052757 nitrogen Inorganic materials 0.000 claims description 53
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 52
• 125000003545 alkoxy group Chemical group 0.000 claims description 40
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 40
• 125000003118 aryl group Chemical group 0.000 claims description 37
• 125000001072 heteroaryl group Chemical group 0.000 claims description 35
• 150000003839 salts Chemical class 0.000 claims description 33
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 23
• 125000000217 alkyl group Chemical group 0.000 claims description 23
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 21
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• 229910052799 carbon Inorganic materials 0.000 claims description 14
• 229910052760 oxygen Inorganic materials 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 239000000460 chlorine Substances 0.000 claims description 11
• 229910052801 chlorine Inorganic materials 0.000 claims description 11
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
• 230000002401 inhibitory effect Effects 0.000 claims description 10
• 125000006239 protecting group Chemical group 0.000 claims description 10
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 8
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 6
• 229910052731 fluorine Chemical group 0.000 claims description 6
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
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• 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
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• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 4
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 3
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• KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 2
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• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
• 125000003275 alpha amino acid group Chemical group 0.000 claims 3
• 238000011282 treatment Methods 0.000 abstract description 31
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• 239000000243 solution Substances 0.000 description 175
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• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 83
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• 235000019257 ammonium acetate Nutrition 0.000 description 78
• 229940043376 ammonium acetate Drugs 0.000 description 78
• 230000014759 maintenance of location Effects 0.000 description 78
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
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• 239000011541 reaction mixture Substances 0.000 description 70
• 235000019439 ethyl acetate Nutrition 0.000 description 67
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 44
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