Two-dimensional libraries of 4-acylamino-1,3-thiazoles 9 were prepared via Curtius rearrangement of 1,3-thiazole-4-carbonyl azides 6, trapping of the intermediate isocyanates with oxime resin, and thermal regeneration of the isocyanates from the washed resin in the presence of nucleophiles. Several compounds proved to be selective inhibitors of CDK5/p25 versus the closely homologous CDK2/cyclin A enzyme, with the best analogue (43) possessing over 100-fold selectivity.