Identification and synthesis of 2,7-diamino-thiazolo[5,4-d]pyrimidine derivatives as TRPV1 antagonists

Abstract We have identified and synthesized a series of 2,7-diamino-thiazolo[5,4- d ]pyrimidines as TRPV1 antagonists. An exploration of the structure–activity relationships at the 2-, 5-, and 7-positions of the thiazolo[5,4- d ]pyrimidine led to the identification of several potent TRPV1 antagonists, including 3 , 29 , 51 , and 57 . Compound 3 was orally bioavailable and afforded a significant reversal of carrageenan-induced thermal hyperalgesia with an ED 50  = 0.5 mg/kg in rats.