Potent selective thienoxazinone inhibitors of herpes proteases

Thieno[3,2-d]oxazinones are potent, selective, mechanism-based inhibitors of the herpes proteases with good aqueous stability. Specificity between the HSV and CMV proteases varies across the series: compounds 14b and 14c are submicromolar HSV protease inhibitors with modest CMV protease inhibition, 14g is a selective CMV protease inhibitor; and 32 inhibits both enzymes with an IC50 of about 1 μM.