Novel Compounds as Modulators of Ppar

A method for achieving an effect in a patient comprising the administration of a therapeutically effective amount of a therapeutically effective amount of a compound of Formula I;

• wherein:
• A is selected from the group consisting of aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, any of which may be optionally substituted;
• R12 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower heteroalkyl, and lower alkoxy;
• R12 may join together with a carbon atom in G1 to form a five to eight-membered carbocycle or heterocycle, having structural Formula (II):
• B is a saturated, partially saturated, or unsaturated hydrocarbon chain, optionally containing one or more heteroatoms, to form an optionally substituted five- to eight-membered carbocycle or heterocycle;
• T is selected from the group consisting of —C(O)OH, —C(O)NH2, and tetrazole;
• G1 is selected from the group consisting of —(CR1R2)n—, -Z(CR1R2)r—, (CR1R2)rZ—, —(CR1R2)rZ(CR1R2)s—;
• Z is O, S, or NR6;
• n is 1 to 4;
• r and s are 0 to 2;
• R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower alkoxy, and lower perhaloalkyl, or R1 and R2 together may form a cycloalkyl;
• G2 is —Y(CR3R4)pW(CR3R4)m—;
• Y is S, —SO2N(R5)— or NR6;
• W is O, S or —NR6;
• p is 2 to 6:
• m is 0, 1 or 2;
• R3 and R4 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted heteroalkyl, optionally substituted cycloalkyl, lower perhaloalkyl, lower perhaloalkoxy, nitro, cyano, NH2, and —C(O)OR11, or R3 and R4 together may form a cycloalkyl;
• R11 is selected from the group consisting of hydrogen and optionally substituted lower alkyl;
• R5 and R6 are each independently selected from the group consisting of hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted heteroalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
• G3 is selected from the group consisting of hydrogen, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloheteroalkyl, and —N═C(R7R8);
• R7 and R8 are each individually selected from the group consisting of hydrogen, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted cycloheteroalkyl;
• and
• wherein said effect is selected from the group consisting of modulation of PPARδ, upregulation of expression of GLUT4 in adipose tissue, reduction of expression of NPC1L1, raising of HDL, lowering of LDLc, shifting of LDL particle size from small dense to normal LDL, inhibition of cholesterol absorption, reduction of triglycerides, decrease of insulin resistance, lowering of blood pressure, promotion of wound healing, reduction of scarring, end treatment of a PPARδ-mediated disease.