发明名称 Compounds
摘要 The present invention relates to novel NADPH oxidase II inhibitors and their use in the treatment of diseases mediated by the NADPH oxidase enzymes.
申请公布号 US8877742(B2) 申请公布日期 2014.11.04
申请号 US201214119900 申请日期 2012.06.08
申请人 GlaxoSmithKline Intellectual Property Limited 发明人 Chen Deborah W.;Duncan Sarah;King Nigel Paul;Lee Kiew Ching;Mak Sing Yeung;Rivers Dean Andrew
分类号 C07D471/04;C07D498/04 主分类号 C07D471/04
代理机构 代理人 Chen Haiyan;Majarian William M;Battle Carl W
主权项 1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof wherein: R1 is selected from the group consisting of: H,C1-C6 alkyl optionally substituted with cycloalkyl or C1-C3 alkoxy substituted with trimethylsilyl,(CH2)kNRaRa, wherein Ra is optionally substituted with halo or NRaRa,(CH2)mRb, wherein Rb is optionally substituted with C1-C3 alkyl, C1-C3 alkoxy or C(O)ORa, andbenzyl optionally substituted with C1-C3 alkoxy, halo or C1-C3 alkyl; R2 is selected from the group consisting of: H, halo, CN, (CH2)nNRaRa, C(O)NRaRa, C(O)ORa, NRaC(O)Ra, (CH2)sORa,C1-C6 alkyl optionally substituted with Rb,indoline optionally substituted with C1-C3 alkyl or halo,C2-C6 alkynyl optionally substituted with OH, C1-C3 alkoxy, NRaRa or Rb,(CH2)nRb, wherein Rb is optionally substituted with C1-C3 alkyl,C(O)Rb, wherein Rb is optionally substituted with C1-C3 alkyl,(CH2)nRc wherein Rc is optionally substituted with one or more substituents selected from the group consisting of C1-C3 alkoxy, C1-C3 alkyl, NRaRa and halo, and(CH2)nRd wherein Rd is optionally substituted with one or more substituents selected from the group consisting of C1-C3 alkoxy, C1-C3 alkyl, NRaRa and halo; R3 is selected from the group consisting of: H,indoline, wherein said indoline is optionally substituted with one or more substituents selected from the group consisting of 1) C1-C6 alkyl optionally substituted with C3-C5 cycloalkyl or halo, 2) cycloalkyl substituted with C1-C3 alkyl, 3) halo, 4) C1-C3 alkoxy, 5) (CH2)tOH, and 6) ═O,indole optionally substituted with one or more 1) C1-C3 alkyl optionally substituted with halo, 2) halo, or 3) C1-C3 alkoxy,indazole optionally substituted with C1-C3 alkyl or halo,(CH2)tRc wherein Rc is optionally substituted with one or more substituents selected from the group consisting of: 1) Rb optionally substituted with C1-C3 alkyl, C(O)ORa or ═O,2) C1-C3 alkoxy,3) C1-C4 alkyl optionally substituted with one to three F,4) (CH2)tNRaC(O)ORa,5) (CH2)tNRaRa,6) halo,7) —S—CH3,8) —S(O)CH3, and9) Rd,(CH2)tRd wherein Rd is optionally substituted with one or more substituents selected from the group consisting of C1-C4 alkyl, C1-C3 alkoxy, halo, Rb, and (CH2)tNRaRa optionally substituted with dimethylamino; R4 is selected from the group consisting of: C1-C3 alkyl optionally substituted with cycloalkyl,C3-C5 cycloalkyl,Rb optionally substituted with one or more substituents selected from the group consisting of: 1) C1-C3 alkyl, 2) halo, 3) (CH2)vNRaRa, 4) (CH2)vCF3, 5) C(O)CH3 and 6) benzylcarboxylate,Rc optionally substituted with one or more substituents selected from the group consisting of: 1) halo, 2) CN, 3) C1-C3 alkoxy, 4) Rb optionally substituted with C1-C3 alkyl, and 5) (CH2)vNRaRa, andRd optionally substituted with one or more substituents selected from the group consisting of: 1) C1-C3 alkyl, 2) C1-C3 alkoxy, 3) CF3, 4) halo, and 5) Rb optionally substituted with C1-C3 alkyl; R5 is H, C1-C3 alkyl or halo; each Ra is C1-C6 alkyl, C3-C5 cycloalkyl or H; each Rb is heterocycloalkyl; each Rc is phenyl; each Rd is heteroaryl; s is 1 or 2; k is 2 or 3; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; t is 0, 1, 2 or 3; and v is 0, 1, 2 or 3.
地址 Brentford, Middlesex GB