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COMPOUNDS AND COMPOSITIONS AS HEDGEHOG PATHWAY MODULATORS

  • US 20090203666A1
  • Filed: 05/04/2007
  • Published: 08/13/2009
  • Est. Priority Date: 05/05/2006
  • Status: Active Grant
First Claim
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1. A compound of Formula I:

  • in which;

    Y1 and Y2 are independently selected from N and CR10;

    wherein R10 is selected from hydrogen, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy and —

    OXNR10aR10b;

    wherein R10a and R10b are independently selected from hydrogen and C1-6alkyl;

    R1 is selected from cyano, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy, C6-10aryl, dimethyl-amino, C1-6alkyl-sulfanyl and C3-8heterocycloalkyl optionally substituted with up to 2 C1-6alkyl radicals;

    R2 and R5 are independently selected from hydrogen, cyano, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy and dimethylamino;

    R3 and R4 are independently selected from hydrogen, halo, cyano, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy and halosubstituted-C1-6alkoxy;

    or either R1 and R2 or R1 and R5 together with the phenyl to which they are both attached form C5-10heteroaryl;

    R6 and R7 are independently selected from hydrogen, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy and halosubstituted-C1-6alkoxy;

    with the proviso that R6 and R7 are not both hydrogen;

    R8 is selected from hydrogen, halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy and halosubstituted-C1-6alkoxy;

    R9 is selected from —

    S(O)2R11, —

    C(O)R11, —

    NR12aR12b and —

    R11;

    wherein R11 is selected from aryl, heteroaryl, cycloalkyl and heterocycloalkyl;

    R12a and R12b are independently selected from C1-6alkyl and hydroxy-substituted-C1-6alkyl;

    wherein said aryl, heteroaryl, cycloalkyl and heterocycloalkyl of R9 can be optionally substituted with 1 to 3 radicals independently selected from C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy, C6-10aryl-C0-4alkyl, C5-10heteroaryl-C0-4alkyl, C3-12cycloalkyl and C3-8heterocycloalkyl;

    wherein said aryl-alkyl substituent of R9 is optionally substituted with 1 to 3 radicals independently selected from halo, C1-6alkyl, halosubstituted-C1-6alkyl, C1-6alkoxy, halosubstituted-C1-6alkoxy and methyl-piperazinyl;

    and the pharmaceutically acceptable salts, hydrates, solvates and isomers thereof.

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