CA2663100A1 - Indazole derivatives as modulators of interleukin-1 receptor-associated kinase - Google Patents

Info

Publication number

CA2663100A1

CA2663100A1 CA002663100A CA2663100A CA2663100A1 CA 2663100 A1 CA2663100 A1 CA 2663100A1 CA 002663100 A CA002663100 A CA 002663100A CA 2663100 A CA2663100 A CA 2663100A CA 2663100 A1 CA2663100 A1 CA 2663100A1

Authority

CA

Canada

Prior art keywords

compound

optionally substituted

indazol

alkyl

benzo

Prior art date

2006-09-07

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

• 108010072621 Interleukin-1 Receptor-Associated Kinases Proteins 0.000 title abstract description 26
• 102000006940 Interleukin-1 Receptor-Associated Kinases Human genes 0.000 title abstract description 26
• 125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 title description 3
• 238000000034 method Methods 0.000 claims abstract description 45
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
• 102100036342 Interleukin-1 receptor-associated kinase 1 Human genes 0.000 claims abstract description 10
• 101710199015 Interleukin-1 receptor-associated kinase 1 Proteins 0.000 claims abstract description 10
• 230000001404 mediated effect Effects 0.000 claims abstract description 10
• 150000001875 compounds Chemical class 0.000 claims description 180
• -1 hydroxy, amino Chemical group 0.000 claims description 117
• 125000000217 alkyl group Chemical group 0.000 claims description 83
• 125000001072 heteroaryl group Chemical group 0.000 claims description 83
• 125000001931 aliphatic group Chemical group 0.000 claims description 71
• 125000003118 aryl group Chemical group 0.000 claims description 68
• 125000003368 amide group Chemical group 0.000 claims description 36
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 35
• 125000005843 halogen group Chemical group 0.000 claims description 32
• 125000003545 alkoxy group Chemical group 0.000 claims description 30
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 30
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 25
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
• 239000003814 drug Substances 0.000 claims description 18
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
• 229940124597 therapeutic agent Drugs 0.000 claims description 17
• 238000011282 treatment Methods 0.000 claims description 17
• 125000002252 acyl group Chemical group 0.000 claims description 15
• 229910052739 hydrogen Inorganic materials 0.000 claims description 15
• 125000003435 aroyl group Chemical group 0.000 claims description 14
• 125000003107 substituted aryl group Chemical group 0.000 claims description 14
• 229940124530 sulfonamide Drugs 0.000 claims description 14
• 150000003456 sulfonamides Chemical class 0.000 claims description 14
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 13
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 13
• 125000004104 aryloxy group Chemical group 0.000 claims description 12
• 125000005553 heteroaryloxy group Chemical group 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
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 12
• 239000004202 carbamide Substances 0.000 claims description 11
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• 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 7
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• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
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• 125000002947 alkylene group Chemical group 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 125000000623 heterocyclic group Chemical group 0.000 claims description 5
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
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• 229930105110 Cyclosporin A Natural products 0.000 claims description 4
• 108010036949 Cyclosporine Proteins 0.000 claims description 4
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 claims description 4
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• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
• 229960001940 sulfasalazine Drugs 0.000 claims description 4
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 claims description 4
• FETDUDQELDASEU-UHFFFAOYSA-N 3-[2-[[5-(4-methoxypyridin-3-yl)-1h-indazol-3-yl]amino]benzimidazol-1-yl]propan-1-ol Chemical compound COC1=CC=NC=C1C1=CC=C(NN=C2NC=3N(C4=CC=CC=C4N=3)CCCO)C2=C1 FETDUDQELDASEU-UHFFFAOYSA-N 0.000 claims description 3
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• 125000001246 bromo group Chemical group Br* 0.000 claims description 3
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• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
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• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
• LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 2
• XNNSMLBQCJOFTI-UHFFFAOYSA-N 4-[5-(hydroxymethyl)-2-[[5-(4-methoxypyridin-3-yl)-1h-indazol-3-yl]amino]benzimidazol-1-yl]cyclohexan-1-ol Chemical compound COC1=CC=NC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(CO)C=C4N=3)C3CCC(O)CC3)C2=C1 XNNSMLBQCJOFTI-UHFFFAOYSA-N 0.000 claims description 2
• XHVAWZZCDCWGBK-WYRLRVFGSA-M Aurothioglucose Chemical compound OC[C@H]1O[C@H](S[Au])[C@H](O)[C@@H](O)[C@@H]1O XHVAWZZCDCWGBK-WYRLRVFGSA-M 0.000 claims description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
• VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 claims description 2
• 108010008165 Etanercept Proteins 0.000 claims description 2
• 208000035690 Familial cold urticaria Diseases 0.000 claims description 2
• 108010072051 Glatiramer Acetate Proteins 0.000 claims description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
• RCDOOVVHRGUAKF-UHFFFAOYSA-N [1-cyclohexyl-2-[[5-(4-methoxypyridin-3-yl)-1h-indazol-3-yl]amino]benzimidazol-5-yl]methanol Chemical compound COC1=CC=NC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(CO)C=C4N=3)C3CCCCC3)C2=C1 RCDOOVVHRGUAKF-UHFFFAOYSA-N 0.000 claims description 2
• FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 claims description 2
• AUJRCFUBUPVWSZ-XTZHGVARSA-M auranofin Chemical compound CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O AUJRCFUBUPVWSZ-XTZHGVARSA-M 0.000 claims description 2
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• 229960002170 azathioprine Drugs 0.000 claims description 2
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• 229960001334 corticosteroids Drugs 0.000 claims description 2
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• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
• XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 claims description 2
• 229960004171 hydroxychloroquine Drugs 0.000 claims description 2
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• KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 claims description 2
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• AXZVEOQAICRWJY-UHFFFAOYSA-N 1-(4-hydroxycyclohexyl)-2-[[5-(2-methoxyphenyl)-1h-indazol-3-yl]amino]-n-(3-methylbutyl)benzimidazole-5-carboxamide Chemical compound COC1=CC=CC=C1C1=CC=C(NN=C2NC=3N(C4=CC=C(C=C4N=3)C(=O)NCCC(C)C)C3CCC(O)CC3)C2=C1 AXZVEOQAICRWJY-UHFFFAOYSA-N 0.000 claims 1
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