Novel PPAR-gamma agonists as agents for the treatment of type II diabetes

A compound of the formula:

• 16
• or the pharmaceutically acceptable non-toxic salts thereof wherein:
• Z is a 5 or 6 membered aryl or heteroaryl ring optionally substituted with up to three groups selected from lower alkyl, halogen or lower alkoxy;
• n and m independently represent 0, 1 or 2;
• A is C02R9;
• or
• A is
• 17
• D, F and G are the same or different and represent hydrogen, NR1R12, OR1, CH2R1 or SR1;
• R1 and R12 are the same or different and represent hydrogen, lower alkyl, R10C═O, R10SO2, or
• cycloalkyl optionally substituted with one, two, three or four groups independently selected from halogen, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxyl, alkoxycarboxy, alkylcarboxy, hydroxy, lower alkyl, lower alkoxy, amino, or mono or dialkylamino where each alkyl portion is lower alkyl, or
• aryl, heteroaryl, arylalkyl, or heteroarylalkyl, where the ring portion of each is optionally substituted with one, two, three or four groups independently selected from halogen, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxyl, alkoxycarboxy, alkylcarboxy, hydroxy, lower alkyl, lower alkoxy, amino, or mono or dialkylamino where each alkyl portion is lower alkyl;
• R10 is hydrogen or lower alkyl, or aryl, heteroaryl, arylalkyl or heteroarylalkyl, where the ring portion of each is optionally substituted with one, two or three groups independently selected from halogen, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxyl, alkoxycarboxy, alkylcarboxy, hydroxy, lower alkyl, lower alkoxy, amino, or mono or dialkylamino where each alkyl portion is lower alkyl;
• R9 is H or lower alkyl;
• X is N, O, CH2, S, SO or SO2;
• R4 is O, hydrogen, hydroxy, lower alkyl, lower alkoxy, cycloalkyl, R10C═O or R10SO2;
• Y is hydrogen, NR1R12, OR1, CH2R1, SR1, SOR1 or SO2R1;
• and
• R5, R6 and R8, are the same or different and represent hydrogen, lower alkyl, R10C═O, R10SO2, or
• cycloalkyl optionally substituted with one, two, three or four groups independently selected from halogen, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxyl, alkoxycarboxy, alkylcarboxy, hydroxy, lower alkyl, lower alkoxy, amino, or mono or dialkylamino where each alkyl portion is lower alkyl, or
• aryl, heteroaryl, arylalkyl, or heteroarylalkyl, where the ring portion of each is optionally substituted with one, two, three or four groups independently selected from halogen, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxyl, alkoxycarboxy, alkylcarboxy, hydroxy, lower alkyl, lower alkoxy, amino, or mono or dialkylamino where each alkyl portion is lower alkyl;
• or
• R5 and R6 together with the carbon atom to which they are attached form a 5, 6, or 7 membered carbocyclic ring up to two of which members are optionally hetero atoms selected from oxygen, sulfur and nitrogen.