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ω-Carboxyaryl substituted diphenyl ureas as raf kinase inhibitors

DC
  • US 7,351,834 B1
  • Filed: 01/12/2000
  • Issued: 04/01/2008
  • Est. Priority Date: 01/13/1999
  • Status: Expired due to Term
First Claim
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1. A compound of Formula I:


  • A—

    D—

    B 



    (I)or a pharmaceutically acceptable salt thereof, whereinD is —

    NH—

    C(O)—

    NH—

    ,A is a substituted moiety of the formula;




    L—

    M—

    L1,wherein L is phenyl, optionally substituted by halogen, up to per-halo, and Wn, where n is 0-3;

    wherein each W is independently selected from the group consisting of C1-C5 linear or branched alkyl, C1-C5 linear or branched haloalkyl up to perhaloalkyl and C1-C3 alkoxy L1 is selected from pyridinyl substituted by —

    C(O)Rx, andoptionally substituted with 1-3 additional substituents independently selected from the group consisting of R7 and halogen;

    wherein Rx is NRaRb and Ra and Rb areA) independentlya) hydrogen,b) C1-C10 alkyl,c) C6 aryl,d) pyridinyle) substituted C1-10 alkyl,f) substituted C6 aryl,g) substituted pyridinylh) -phenylpiperazine(pyridinyl),i) -phenylmorpholinyl,j) -ethylmorpholinyl,k) -ethylpiperidyl,l) -methyl pyrrolidinyl,m) -methyl tetrahydrofuryl,orn) —

    C2H4NH(phenyl);

    where when Ra and Rb are a substituted group, they are substituted bya) halogen up to per halo,b) hydroxy,c) —

    N(CH3)2,d) C1-C10 alkyl,e) C1-C10 alkoxy,f) halosubstituted C1-6 alkyl, org) —

    OSi(Pr-i)3;

    orB) Ra and Rb together form piperazine or a substituted piperazine with substituents selected from the group consisting ofa) halogen,b) hydroxy,c) C1-10 alkyl,d) pyridinyle) C1-10 alkoxy,f) C6 aryl,g) halo substituted C6 aryl, andh) N-(4-acetylphenyl);

    M is selected from the group consisting of oxygen and sulfur;

    andB isphenyl, substituted with 1-3 substituents independently selected from the group consisting of halogen and R7,and R7 is(a) C1-C6 linear or branched alkyl, optionally substituted with 1-3 halogen substituents;

    or(b) C1-C6 linear or branched alkoxy.

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