Beta3-Adrenoreceptor agonists, agonist compositions and methods of using

A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and at least one compound having the structure:

• 88
• wherein:
• R1 and R3 are independently selected from the group consisting of hydrogen, halogen, alkyl, aryl alkyl, CF3, and OCH3;
• R2 is selected from the group consisting of hydrogen, halogen, OH, OCH3, OCH2COOH, C(O)-aryl, NCS, NH2, N3, NHR8, NHCH2COOH, NHCOR13, NHCONHR13, NHCOSR13;
• R4 and R5 are each independently selected from the group consisting of hydrogen, OH, and halogen;
• R6 and R7 are each independently selected from the group consisting of hydrogen and halogen;
• R8 is selected from the group consisting of hydrogen, lower alkyl of from 1 to about 8 carbons, halogen, OCH3, and CF3;
• R13 is selected from the group consisting of hydrogen, lower alkyl of from 1 to about 8 carbons, phenyl, halogen, OCH3, CF3, and —CH2R′, wherein R′ is halogen;
• or
• wherein R1 and R2 taken together, R2 and R3 taken together, or R4 and R5 taken together form a group having the structure:
• 89
• wherein each R14 is independently selected from the group consisting of hydrogen, lower alkyl of from 1 to about 8 carbons, —C(O)R11, —C(O)SR11, and
• 90
• wherein R11 and R12 are each independently selected from the group consisting of hydrogen and lower alkyl of from 1 to about 8 carbons;
• with the proviso that 1) no more than one of R1, R2, and R3 is OCH3 or hydrogen, 2) when R4 and R5 are OH and R2 is hydrogen, then R1 and R3 are not both CF3, 3) when R4 and R5 are OH and R2 is hydrogen, OH, halogen, OCH3, or NH2, then R1 and R3 are not both halogen, and 3) when R4 and R5 are OH and R2 is NH2 or NHCOR13, then R1 and R3 are not halogen or hydrogen;
• or a pharmaceutically acceptable salt thereof.

A method of stimulating, regulating or modulating metabolism of fats in adipose tissue in animals, comprising administering an effective amount of at least one compound having the structure:

• 92
• wherein:
• R1 and R3 are independently selected from the group consisting of hydrogen, halogen, alkyl, aryl alkyl, CF3, and OCH3;
• R2 is selected from the group consisting of hydrogen, halogen, OH, OCH3, OCH2COOH, C(O)-aryl, NCS, NH2, N3, NHR8, NHCH2COOH, NHCOR13, NHCONHR13, NHCOSR13;
• R4 and R5 are each independently selected from the group consisting of hydrogen, OH, and halogen;
• R6 and R7 are each independently selected from the group consisting of hydrogen and halogen;
• R8 is selected from the group consisting of hydrogen, lower alkyl of from 1 to about 8 carbons, halogen, OCH3, and CF3;
• R13 is selected from the group consisting of hydrogen, lower alkyl of from 1 to about 8 carbons, phenyl, halogen, OCH3, CF3, and —CH2R′, wherein R′ is halogen;
• or
• wherein R1 and R2 taken together, R2 and R3 taken together, or R4 and R5 taken together form a group having the structure:
• 93
• wherein each R14 is independently selected from the group consisting of hydrogen, lower alkyl of from 1 to about 8 carbons, —C(O)R11, —C(O)SR11, and
• 94
• wherein R1 and R12 are each independently selected from the group consisting of hydrogen and lower alkyl of from 1 to about 8 carbons;
• with the proviso that 1) no more than one of R1, R2, and R3 is OCH3 or hydrogen, 2) when R4 and R5 are OH and R2 is hydrogen, then R1 and R3 are not both CF3, 3) when R4 and R5 are OH and R2 is hydrogen, OH, halogen, OCH3, or NH2, then R1 and R3 are not both halogen, and 3) when R4 and R5 are OH and R2 is NH2 or NHCOR13, then R1 and R3 are not halogen or hydrogen;
• or a pharmaceutically acceptable salt thereof.