[EN] N-(IMIDAZO[1,2-B]PYRIDAZIN-3-YL)-1-CYCLOHEXYL-2H-INDAZOLE-5-CARBOXAMIDE AND N-(PYRAZOLO[1,5-A]PYRIMIDIN-3-YL)-1-CYCLOHEXYL-2H-INDAZOLE-5-CARBOXAMIDE DERIVATIVES AS IRAK4 INHIBITORS FOR THE TREATMENT OF ASTHMA<br/>[FR] DÉRIVÉS DE N-(IMIDAZO[1,2-B]PYRIDAZIN-3-YL)-1-CYCLOHEXYL-2H-INDAZOLE-5-CARBOXAMIDE ET DE N-(PYRAZOLO[1,5-A]PYRIMIDIN-3-YL)-1-CYCLOHEXYL-2H-INDAZOLE-5-CARBOXAMIDE UTILISÉS EN TANT QU'INHIBITEURS D'IRAK4 POUR LE TRAITEMENT DE L'ASTHME
申请人:ASTRAZENECA AB
公开号:WO2022122876A1
公开(公告)日:2022-06-16
The present application relates to a compound of Formula (A),wherein R1 is selected from Formula (II) and Formula (III) and R2 is selected from Formula (IV), Formula (V) and Formula (VI) as IRAK4 inhibitors for use in methods of treatment of e.g. asthma and chronic obstructive pulmonary disease (COPD), cancer, inflammatory diseases, and autoinflammatory/autoimmune diseases such as e.g. systemic lupus erythematosus, rheumatoid arthritis, myositis, Sjogren's syndrome, systemic sclerosis, gout, endometriosis, atopic dermatitis and psoriasis. Preferred compounds of the present invention are e.g.: • N-(imidazo[1,2-b]pyridazin-3-yl)-1-cyclohexyl-2H-indazole-5- carboxamide, • N-(pyrazolo[1,5-a]pyrimidin-3-yl)-1-cyclohexyl-2H-indazole-5- carboxamide, • N-(imidazo[1,2-b]pyridazin-3-yl)-1-azaspiro[4.5]decan-8-yl-2H- indazole-5-carboxamide, and • N-(pyrazolo[1,5-a]pyrimidin-3-yl)-1-azaspiro[4.5]decan-8-yl-2H- indazole-5-carboxamide derivatives. An exemplary compound of the present invention is e.g. N- (imidazo[1,2-b]pyridazin-3-yl)-6-methoxy-2-((5r,8r)-1-methyl-2-oxo-1- azaspiro[4.5]decan-8-yl)-2H-indazole-5-carboxamide (Example 1): Formula (VII).
本申请涉及一种化合物,其化学式为(A),其中R1从化学式(II)和化学式(III)中选择,R2从化学式(IV)、化学式(V)和化学式(VI)中选择,作为IRAK4抑制剂用于治疗哮喘和慢性阻塞性肺疾病(COPD)、癌症、炎症性疾病以及自身免疫性疾病,如系统性红斑狼疮、类风湿性关节炎、肌炎、干燥综合症、系统性硬化症、痛风、子宫内膜异位症和银屑病等。本发明的优选化合物包括:•N-(咪唑并[1,2-b]吡嗪-3-基)-1-环己基-2H-吲唑-5-羧酰胺、•N-(吡唑并[1,5-a]嘧啶-3-基)-1-环己基-2H-吲唑-5-羧酰胺、•N-(咪唑并[1,2-b]吡嗪-3-基)-1-氮杂螺[4.5]癸烷-8-基-2H-吲唑-5-羧酰胺和•N-(吡唑并[1,5-a]嘧啶-3-基)-1-氮杂螺[4.5]癸烷-8-基-2H-吲唑-5-羧酰胺衍生物。本发明的一种示例化合物是N-(咪唑并[1,2-b]吡嗪-3-基)-6-甲氧基-2-((5r,8r)-1-甲基-2-氧代-1-氮杂螺[4.5]癸烷-8-基)-2H-吲唑-5-羧酰胺(实例1):化学式(VII)。