Heterocyclic compounds for the inhibition of PASK

A method for achieving an effect in a patient comprising the administration of a therapeutically effective amount of a compound of structural Formula I to a patient in need of any one or more of a reduction in cholesterol and/or a reduction in triglycerides and/or a reduction in hemoglobin A1c:

• or a pharmaceutically acceptable salt, or ester thereof, wherein:
• X1 and X2 are each N;
• R1 and R2 are each independently selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and NR5R6, any of which may be optionally substituted, with the proviso that at least one of R1 or R2 is NR5R6;
• R3 is hydrogen;
• R4 is selected from the group consisting of COOR7, CONR8R9, CONR10OR11, and tetrazolyl;
• R5 and R6 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C7 cycloalkyl, C1-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;
• R7, R8, R9, R10, and R11 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, aryl, heteroaryl, aralkyl and heteroaralkyl, any of which may be optionally substituted;
• R18 and R19 are independently selected from the group consisting of cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, any of which may be optionally substituted;
• and
• m and n are each independently an integer from 0 to 2,
• wherein the effect is selected from the group consisting of reduction of triglycerides, reduction of cholesterol, and reduction of hemoglobin A1c.