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: 1
or an optical isomer, enantiomer, diastereomer, racemate or racemic
mixture thereof, ester, prodrug or metabolite form, or a pharmaceutically
acceptable salt thereof, wherein R.sup.1, R.sup.2 and/or R.sup.3 are
independently hydrogen atoms or alkyl groups and G.sup.1 and G.sup.2 are
aryl, heteroaryl, alkyl, arylalkanyl, arylalkenyl, arylalkynyl,
heteroarylalkanyl, heteroarylalkenyl, or heteroarylalkynyl moieties.
