Abstract: A novel class of compounds has been identified that inhibit PTP-1B through a newly discovered binding interaction. Methods of treating, preventing or delaying the onset of, conditions mediated by PTP-1B are also provided. The compounds are capable of interacting with the primary binding pocket of PTP-1B via a hydrogen bond acceptor and have an aqueous phase free energy more positive than about ?1200 kJ/mol. Representative compounds in the class are those of Formula I: or an optical isomer, enantiomer, diastereomer, racemate or racemic mixture thereof, ester, prodrug or metabolite form, or a pharmaceutically acceptable salt thereof, wherein R1, R2 and/or R3 are independently hydrogen atoms or alkyl groups and G1 and G2 are aryl, heteroaryl, alkyl, arylalkanyl, arylalkenyl, arylalkynyl, heteroarylalkanyl, heteroarylalkenyl, or heteroarylalkynyl moieties.