Thiazolo-naphthyl acids

A method of modulating PAI-1 activity comprising identifying a subject in need of PAI-1 modulation and administering to the subject an effective amount of a compound of the formula 1:

• or a solvate, hydrate or pharmaceutically acceptable salt or ester form thereof;
• wherein:
• Ar is aryl or heteroaryl;
• R1 is hydrogen, C1-C12 alkyl, C6-14 aryl, C6-14ar(C1-6)alkyl, —(CH2)p-heteroaryl, —(CH2)p—CO-aryl, —(CH2)p—CO-heteroaryl, —(CH2)p—CO—(C1-C6)alkyl, C2-C7 alkenyl, C2-C7 alkynyl, C3-C8 cycloalkyl, halogen, or C1-C3 perfluoroalkoxy;
• R2 and R3 are independently hydrogen, C1-C12 alkyl, C6-14 aryl, C6-14ar(C1-6)alkyl, —(CH2)p-heteroaryl, halogen, C1-C6 alkoxy, aralkyl, alkoxyaryl, nitro, carboxy(C1-C6 alkyl), carbamide, carbamate, or C3-C8 cycloalkyl;
• R4 is —CH(R6)(CH2)nR5, —C(CH3)2R6, —CH(R5)(CH2)nR6, —CH(R5)C6H4R6, —CH(R5)C6H3(CO2H)2, CH(R5)C6H2(CO2H)3, or an acid mimic;
• R5 is hydrogen, C1-C6 alkyl, C6-C12 aryl, aralkyl, C3-C8 cycloalkyl, or —(CH2)n(R7);
• R6 is CO2H, tetrazole, or PO3H;
• R7 is
• n is from 0 to 6;
• p is from 0 to 3;
• b is from 0 to 6;
• and
• a is from 0 to 6.