×

BICYCLIC, SUBSTITUTED TRIAZOLES AS MODULATORS OF PPAR AND METHODS OF THEIR PREPARATION

  • US 20060014785A1
  • Filed: 05/24/2005
  • Published: 01/19/2006
  • Est. Priority Date: 05/25/2004
  • Status: Abandoned Application
First Claim
Patent Images

1. A compound having the formula:

  • embedded image wherein Ar1 is a monocyclic or bicyclic aromatic ring system selected from the group consisting of phenyl, naphthyl, imidazolyl, benzimidazoyl, pyrrolyl, indolyl, thienyl, benzothienyl, furanyl, benzofuranyl, and benzodioxole each of which is optionally substituted with from one to five R7 substituents independently selected from the group consisting of halogen, (C1-C8)alkyl, halo(C1-C8)alkyl, —

    OR2, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C4)alkyl, aryl, aryl(C1-C4)alkyl, aryl(C2-C8)alkenyl, aryl(C2-C8)alkynyl, heterocyclyl, heterocyclyl(C1-C4)alkyl, —

    COR2, —

    CO2R2, —

    NR2R3, —

    NO2, —

    CN, —

    S(O)r1R2;



    X1OR2, —

    X1COR2, —

    X1CO2R2, —

    X1NR2R3, —

    X1NO2, —

    X1CN, and —

    X1S(O)r1R2;

    Ar2 is a bicyclic aromatic ring system selected from the group having the formula;

    embedded imagewherein the dashed line indicates that the bond may be a double or single bond;

    each of which is optionally substituted with from one to four R8 substituents independently selected from the group consisting of halogen, (C1-C8)alkyl, halo(C1-C8)alkyl, —

    OR2, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C4)alkyl, aryl, aryl(C1-C4)alkyl, aryl(C2-C8)alkenyl, aryl(C2-C8)alkynyl, heterocyclyl, heterocyclyl(C1-C4)alkyl, —

    COR2, —

    CO2R2, —

    NR2R3, —

    NO2, —

    CN, —

    S(O)r1R25;



    X2OR2, —

    X2COR2O—

    X2CO2R2, —

    X2NR2R3, —

    X2NO2, —

    X2CN, and —

    X2S(O)r1R2;

    L is a member selected from the group consisting of a covalent bond and a linking group having from one to six main chain atoms and having the formula —

    Y1m1Y2m2Y3m3

    wherein L can be attached to any available ring member of Ar2;

    K is a member selected from the group consisting of a covalent bond and a linking group having from one to six main chain atoms and having the formula —

    Y4m4Y5m5Y6m6

    wherein K can be attached to any available ring member of Ar2;

    each Y1, Y2, Y3, Y4, Y5, and Y6 is a member independently selected from the group consisting of (CR4R5)p, C═

    O, C═

    ONR2, C═

    NOR2, NR2C═

    O, NR2, O, S(O)r2, NR2SO2, and SO2NR2;

    Z is selected from the group consisting of CH2OR6, CO2R6, CN, tetrazol-5-yl, CONHSO2R2 and CHO;

    R1 is selected from the group consisting of H, halogen, (C1-C8)alkyl, halo(C1-C8)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C4)alkyl, aryl, aryl(C1-C4)alkyl, heterocyclyl, and heterocyclyl(C1-C4)alkyl;

    each R2 and R3 is a member independently selected from the group consisting of H, (C1-C8)alkyl, halo(C1-C8)alkyl, —

    X3OR9, aryl, aryl(C1-C4)alkyl, and heteroaryl, or optionally, if both present on the same substituent, may be joined together to form a three- to eight-membered ring system;

    each R4 and R5 is a member independently selected from the group consisting of H, halogen, (C1-C8)alkyl, halo(C1-C8)alkyl, OR2, aryl, heteroaryl, and aryl(C1-C4)alkyl, or optionally, if both present on the same substituent, may be joined together to form a three- to eight-membered ring system, or if present on adjacent carbon atoms are combined to form a double bond or triple bond between the atoms to which they are attached;

    R6 is a member selected from the group consisting of H, (C1-C8)alkyl, halo(C1-C8)alkyl, —

    X4OR2, —

    X4NR2R3, (C2-C8)alkenyl, (C3-C7)cycloalkyl, heterocyclyl, aryl(C1-C4)alkyl; and

    aryl(C2-C8)alkenyl;

    R9 is a member selected from the group consisting of H, (C1-C8)alkyl, halo(C1-C8)alkyl, aryl, aryl(C1-C4)alkyl, and heteroaryl;

    each X1, X2, X3, and X4 is a member independently selected from the group consisting of (C1-C4)alkylene, (C2-C4)alkenylene, and (C2-C4)alkynylene;

    the subscripts m1, m2, m3, m4, m5 and m6 are each integers of from 0 to 1;

    the subscripts r1 and r2 are integers of from 0 to 2;

    the subscript p is an integer of from 1 to 2; and

    pharmaceutically acceptable salts, solvates, hydrates and prodrugs thereof.

View all claims
  • 1 Assignment
Timeline View
Assignment View
    ×
    ×