IKK-BETA SERINE-THREONINE PROTEIN KINASE INHIBITORS
    5.
    发明申请
    IKK-BETA SERINE-THREONINE PROTEIN KINASE INHIBITORS 失效
    IKK-BETA丝氨酸蛋白激酶激酶抑制剂

    公开(公告)号:US20100087515A1

    公开(公告)日:2010-04-08

    申请号:US12513206

    申请日:2007-10-29

    CPC分类号: C07D333/38

    摘要: Compounds of formula (IA) or (IB) are inhibitors of IkB kinase (IKK) activity, and are useful in the treatment of autoimmune and inflammatory diseases: Formula (A) and (B) wherein R7 is hydrogen or optionally substituted (C1-C6)alkyl; ring A is an optionally substituted aryl or heteroaryl ring of 5-13 ring atoms; Z is (a) a radical of formula R1R2CHNH—Y-L1-X1—(CH2)z— wherein: z is 0 or 1; R1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular esterase enzymes to a carboxylic acid group; R2 is the side chain of a natural or non-natural alpha amino acid; Y is a bond, —C(═O)—, —S(═P)2-, —C(═O)O—, —C(═O)NR3-, —C(═S)—NR3, —C(═NH)—NR3 or —S(═O)2NR3— wherein R3 is hydrogen or optionally substituted C1-C6 alkyl; L is a divalent linker radical of formula -(Alk1)m(Q)(Alk2)p- wherein m, n, p, Q, AIk1 and AIk2 are as defined in the claims.

    摘要翻译: 式(IA)或(IB)的化合物是IkB激酶(IKK)活性的抑制剂,可用于治疗自身免疫性和炎性疾病:式(A)和(B)其中R 7为氢或任选取代的(C1- C6)烷基; 环A是任选取代的5-13个环原子的芳基或杂芳基环; Z是(a)式R1R2CHNH-Y-L1-X1-(CH2)z-的基团,其中:z为0或1; R 1是羧酸基团(-COOH)或可被一个或多个细胞内酯酶水解成羧酸基团的酯基; R2是天然或非天然α氨基酸的侧链; Y是键,-C(= O) - , - S(= O)2 - , - C(= O)O-,-C(= O)NR 3 - , - C(= NH)-NR 3或-S(= O)2 NR 3 - ,其中R 3是氢或任选取代的C 1 -C 6烷基; L1是式 - (Alk1)m(Q)(Alk2)p的二价连接基团,其中m,n,p,Q,Alk1和Alk2如权利要求中所定义。