Treatment for obesity

A method for treating a condition selected from the group consisting of obesity, overweight, type II diabetes and the metabolic syndrome in a mammal, comprising administering to a mammalian subject in need thereof:

• (a) a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula I:
• or an enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt, solvate, ester or pro-drug thereof that is effective in the treatment or prevention of a condition selected from the group consisting of obesity, overweight, type II diabetes and the metabolic syndrome in a mammal, and
• wherein the symbols have the following meanings and are, for each occurrence, independently selected:
• R1 is hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, aryl or substituted aryl, ORa, SRa, S(═O)2Re, S(═O)2ORe, C(═O)ORd, C(═O)Ra, or C(═O)NRbRc;
• R2 is heterocycle or substituted heterocycle, aryl or substituted aryl;
• R3 is hydrogen, alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocycle or substituted heterocycle, aryl or substituted aryl;
• R4, R7, and R8 are each independently hydrogen, halogen, cyano, nitro, CF3, OCF3, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, aryl or substituted aryl, ORa, SRa, S(═O)Re, S(═O)2Re, P(═O)2Re, S(═O)2ORe, P(═O)2ORe, NRbRc, NRbS(═O)2Re, NRbP(═O)2Re, S(═O)2NRbRc, P(═O)2NRbRc, C(═O)ORe, C(═O)Ra, C(═O)NRbRc, OC(═O)Ra, OC(═O)NRbRc, NRbC(═O)ORe, NRdC(═O)NRbRc, NRdS(═O)2NRbRc, NRdP(═O)2NRbRc, NRbC(═O)Ra, or NRbP(═O)2Re;
• R5 is alkyl or substituted alkyl, heterocycle or substituted heterocycle, aryl or substituted aryl, amino or substituted amino;
• R6 is hydrogen, halogen, cyano, nitro, CF3, OCF3, alkyl or substituted alkyl, heterocycle or substituted heterocycle, aryl or substituted aryl, or ORa;
• Ra is hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, or aryl or substituted aryl;
• Rb, Rc and Rd are independently hydrogen, alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocycle or substituted heterocycle, or aryl or substituted aryl, or said Rb and Rc together with the N to which they are bonded optionally form a heterocycle or substituted heterocycle;
• Re is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, or aryl or substituted aryl;
• and
• (b) a pharmaceutically acceptable excipient, carrier, or diluent.

A method for reducing or ameliorating morbidity or mortality known to be associated with obesity, overweight, type II diabetes and the metabolic syndrome in a mammal, comprising administering to a mammalian subject in need thereof:

• (a) a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula I:
• or an enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt, solvate, ester or pro-drug thereof that is effective in the treatment or prevention of a condition selected from the group consisting of obesity, overweight, type II diabetes and the metabolic syndrome in a mammal, and
• wherein the symbols have the following meanings and are, for each occurrence, independently selected:
• R1 is hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, aryl or substituted aryl, ORa, SRa, S(═O)2Re, S(═O)2ORe, C(═O)ORd, C(═O)Ra, or C(═O)NRbRc;
• R2 is heterocycle or substituted heterocycle, aryl or substituted aryl;
• R3 is hydrogen, alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocycle or substituted heterocycle, aryl or substituted aryl;
• R4, R7, and R8 are each independently hydrogen, halogen, cyano, nitro, CF3, OCF3, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, aryl or substituted aryl, ORa, SRa, S(═O)Re, S(═O)2Re, P(═O)2Re, S(═O)2ORe, P(═O)2ORe, NRbRc, NRbS(═O)2Re, NRbP(═O)2Re, S(═O)2NRbRc, P(═O)2NRbRc, C(═O)ORe, C(═O)Ra, C(═O)NRbRc, OC(═O)Ra, OC(═O)NRbRc, NRbC(═O)ORe, NRdC(═O)NRbRc, NRdS(═O)2NRbRc, NRdP(═O)2NRbRc, NRbC(═O)Ra, or NRbP(═O)2Re;
• R5 is alkyl or substituted alkyl, heterocycle or substituted heterocycle, aryl or substituted aryl, amino or substituted amino;
• R6 is hydrogen, halogen, cyano, nitro, CF3, OCF3, alkyl or substituted alkyl, heterocycle or substituted heterocycle, aryl or substituted aryl, or ORa;
• Ra is hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, or aryl or substituted aryl;
• Rb, Rc and Rd are independently hydrogen, alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocycle or substituted heterocycle, or aryl or substituted aryl, or said Rb and Rc together with the N to which they are bonded optionally form a heterocycle or substituted heterocycle;
• Re is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycle or substituted heterocycle, or aryl or substituted aryl;
• and
• (b) a pharmaceutically acceptable excipient, carrier, or diluent.