Methods and compositions for the treatment of metabolic disorders

A method of treating a lipid disorder comprising administering a therapeutically effective amount of a compound of Formula I:

• wherein:
• R1 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic or —CφHR2R3;
• R2 and R4 are independently H, —(CH2)mNR9R10, —(CH2)mN(CH3)R9R10, —(CH2)mNR9C(═NR9)NR9R10, or —(CH2)m-imidazolidin-2-imin-1-yl;
• R3 is H, —NR9R10, —N(CH3)R9R10, —N(R9)—C(═O)R9, —CφHR9R10, —CφH(R9)—C(═O)R10, or —CφH(C(═O)R9)(C(═O)R10;
• R5 is phenyl, benzyl, —CH2-(4-hydroxy-phenyl), —CH2-(indol-3-yl), —CH2-(indol-4-yl), —CH2-(napht-1-yl), —CH2-(napht-2-yl), —CH2-(aryl), —CH2-(heteroaryl), napht-1-yl, or napht-2-yl;
• R6 is methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, t-butyl, (2S)-butyl, (2R)-butyl, C5-6 alkyl, cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclohexyl, cyclopentylmethyl, or cyclohexylmethyl;
• R7 is —O— or —N(R9)—;
• R8, R9 and R10 are, independently in each instance, H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, or (CH2CH2O)nCH3;
• m is 2, 3, 4 or 5;
• n is an integer of from 1 to 20;
• Cα, Cβ, Cγ, Cε and Cφ are carbon atoms, and the stereochemistries at Cα, Cβ, Cγ, Cε and Cφ are independently either R or S;
• or pharmaceutically acceptable salt, hydrate, solvate, pro-drug or solvate thereof.

A method of treating non-insulin dependent diabetes mellitus comprising administering a therapeutically effective amount of a compound of Formula I:

• wherein:
• R1 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic or —CφHR2R3;
• R2 and R4 are independently H, —(CH2)mNR9R10, —(CH2)mN(CH3)R9R10, —(CH2)mNR9C(═NR9)NR9R10, or —(CH2)m-imidazolidin-2-imin-1-yl;
• R3 is H, —NR9R10, —N(CH3)R9R10, —N(R9)—C(═O)R9, —CφHR9R10, —CφH(R9)—C(═O)R10, or —CφH(C(═O)R9)(C(═O)R10);
• R5 is phenyl, benzyl, —CH2-(4-hydroxy-phenyl), —CH2-(indol-3-yl), —CH2-(indol-4-yl), —CH2-(napht-1-yl), —CH2-(napht-2-yl), —CH2-(aryl), —CH2-(heteroaryl), napht-1-yl, or napht-2-yl;
• R6 is methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, t-butyl, (2S)-butyl, (2R)-butyl, C5-6 alkyl, cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclohexyl, cyclopentylmethyl, or cyclohexylmethyl;
• R7 is —O— or —N(R9)—;
• R8, R9 and R10 are, independently in each instance, H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, or (CH2CH2O)nCH3;
• m is 2, 3, 4 or 5;
• n is an integer of from 1 to 20;
• Cα, Cβ, Cγ, Cε and Cφ are carbon atoms, and the stereochemistries at Cα, Cβ, Cγ, Cε and Cφ are independently either R or S;
• or pharmaceutically acceptable salt, hydrate, solvate, pro-drug or solvate thereof.

A method of treating conditions associated with non-insulin dependent diabetes mellitus comprising administering a therapeutically effective amount of a compound of Formula I:

• wherein:
• R1 is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic or —CφHR2R3;
• R2 and R4 are independently H, —(CH2)mNR9R10, —(CH2)mN(CH3)R9R10, —(CH2)mNR9C(═NR9)NR9R10, or —(CH2)m-imidazolidin-2-imin-1-yl;
• R3 is H, —NR9R10, —N(CH3)R9R10, —N(R9)—C(═O)R9, —CφHR9R10, —CφH(R9)—C(═O)R10, or —CφH(C(═O)R9)(C(═O)R10);
• R5 is phenyl, benzyl, —CH2-(4-hydroxy-phenyl), —CH2-(indol-3-yl), —CH2-(indol-4-yl), —CH2-(napht-1-yl), —CH2-(napht-2-yl), —CH2-(aryl), —CH2-(heteroaryl), napht-1-yl, or napht-2-yl;
• R6 is methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, t-butyl, (2S)-butyl, (2R)-butyl, C5-6 alkyl, cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclohexyl, cyclopentylmethyl, or cyclohexylmethyl;
• R7 is —O— or —N(R9)—;
• R8, R9 and R10 are, independently in each instance, H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, or (CH2CH2O)nCH3;
• m is 2, 3, 4 or 5;
• n is an integer of from 1 to 20;
• Cα, Cβ, Cγ, Cε and Cφ are carbon atoms, and the stereochemistries at Cα, Cβ, Cγ, Cε and Cφ are independently either R or S;
• or pharmaceutically acceptable salt, hydrate, solvate, pro-drug or solvate thereof.