Compounds that modulate the activity of PTP-1B and TC-PTP

A compound having the structure having the structure

• 28
• wherein:
• R1 is hydrogen, methyl, ethyl, or propyl;
• R2 is hydrogen, —S(O2)R3, —NH(C(═O)R3, —NH(C(═O)CH2(C═O)OR3, —S(O2)NR4R5, or —NR4S(O2)R3 where R3 is C1-C5 alkyl, R4 is hydrogen, C1-C5 alkyl, unsubstituted cyclic moiety, or substituted cyclic moiety, and R5 is either hydrogen or R5 and R4 together form an unsubstituted cyclic moiety or a substituted cyclic moiety;
• R6 is hydrogen or alternatively when R2 is —NR4S(O2)NR3, then R6 and R4 together form an unsubstituted cyclic moiety or substituted cyclic moiety;
• and,
• L is —NHS(O2)— or —S(O2)NR7CH2— where R7 is hydrogen or C1-C5 alkyl.

A compound having the structure

• 29
• wherein:
• R10 is C1-C5 alkyl or NHR11 where R11 is hydrogen, C1-C10 alkyl or aryl;
• and,
• L is —NHS(O2)— or —S(O2)N(CH2)3CH2—.

A method of identifying an exosite inhibitor of PTP-1B comprising

• a) contacting a test compound with PTP-1B;
• b) contacting the test compound with an exosite mutant of PTP-1B;
• and
• c) comparing the activity of PTP-1B in the presence of the test compound with the activity of the exosite mutant of PTP-1B in the presence of the test compound.

A method of identifying an exosite inhibitor of TC-PTP comprising

• a) contacting a test compound with TC-PTP;
• b) contacting the test compound with an exosite mutant of TC-PTP;
• and
• c) comparing the activity of TC-PTP in the presence of the test compound with the activity of the exosite mutant of TC-PTP in the presence of the test compound.