Heterocyclic compounds for the inhibition of pask

A method of treatment of a disease comprising the administration of a therapeutically effective amount of a compound having structural formula (IV):

• or a salt, ester or prodrug thereof, wherein:
• X1 is chosen from CH and N;
• X2 is chosen from CH and N;
• R1 and R2 are each independently chosen from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR5, SR5, and NR5R6, any of which may be optionally substituted;
• R4 is chosen from COOR7, NO2, CONR8R9, CONR10OR11, PO3H, SO2NHR5, CONHSO2R5, SO2NH2, CF3, SO3H, SO2NHCOR5, B(OH)2 and tetrazolyl;
• R5 and R6 are each independently chosen from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C3-C7 heterocycloalkyl, aryl, heteroaryl, aralkyl, and heteroaralkyl, any of which may be optionally substituted;
• or taken together, R5 and R6 may form a heterocycloalkyl or heteroaryl, either of which may be optionally substituted;
• and
• R7, R8, R9, R10, and R11 are each independently chosen from hydrogen, C1-C6 alkyl, aryl, heteroaryl, aralkyl and heteroaralkyl, any of which may be optionally substituted;
• to a patient in need thereof.

A method for achieving an effect in a patient comprising the administration of a therapeutically effective amount of a compound having structural formula (IV):

• or a salt, ester or prodrug thereof, wherein:
• X1 is chosen from CH and N;
• X2 is chosen from CH and N;
• R1 and R2 are each independently chosen from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR5, SR5, and NR5R6, any of which may be optionally substituted;
• R4 is chosen from COOR7, NO2, CONR8R9, CONR10OR11, PO3H, SO2NHR5, CONHSO2R5, SO2NH2, CF3, SO3H, SO2NHCOR5, B(OH)2 and tetrazolyl;
• R5 and R6 are each independently chosen from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C3-C7 heterocycloalkyl, aryl, heteroaryl, aralkyl, and heteroaralkyl, any of which may be optionally substituted;
• or taken together, R5 and R6 may form a heterocycloalkyl or heteroaryl, either of which may be optionally substituted;
• and
• R7, R8, R9, R10, and R11 are each independently chosen from hydrogen, C1-C6 alkyl, aryl, heteroaryl, aralkyl and heteroaralkyl, any of which may be optionally substituted;
• to a patient, wherein the effect is selected from the group consisting of reduction of triglycerides, reduction of cholesterol, and reduction of hemoglobin A1c.