Triazolothienopyrimidine compound inhibitors of urea transporters and methods of using inhibitors

摘要

Provided herein are small molecule triazolothienopyrimidine compounds that inhibit urea transport activity of solute transporters, particularly the UT-B transporter. The compounds described herein are useful for increasing solute clearance in states of fluid overload and for treating refractory edema associated with cardiovascular, renal, and metabolic diseases, disorders, and conditions.

主权项

1. A method for treating a disease or disorder treatable by inhibiting transport of urea in a subject, said method comprising administering to the subject a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of structure (I): or a single stereoisomer, a mixture of stereoisomers, tautomer or pharmaceutically acceptable salt thereof, wherein, R1 is optionally substituted aryl or optionally substituted heteroaryl; R2 is —N(R5)(R6); R3 and R4 are each independently hydrogen, alkyl, halo or haloalkyl; R5 is hydrogen or alkyl; and R6 is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclylalkyl, optionally substituted aralkyl, or optionally substituted heteroarylalkyl; or R5 and R6, together with the nitrogen atom to which they are attached, form an optionally substituted N-heterocycle, or optionally substituted N-heteroaryl.