Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase.

Basic Information

ID: ALA1145158

Journal: J Med Chem

Title: Selective substrate-based inhibitors of mammalian dimethylarginine dimethylaminohydrolase.

Authors: Rossiter S, Smith CL, Malaki M, Nandi M, Gill H, Leiper JM, Vallance P, Selwood DL.

Abstract: The enzyme DDAH metabolizes methylarginines that are inhibitors of nitric oxide synthase (NOS). Substrate-based inhibitors of mammalian DDAH have been synthesized, with optimization to give selective inhibition of DDAH with no significant direct effect on NOSs. These are the first examples of reversible DDAH inhibitors with significant activity and selectivity. In vivo administration increases plasma ADMA levels, giving proof of concept that these inhibitors can be used to probe the physiological effects of DDAH inhibition, with potential for pharmaceutical use of DDAH inhibitors in diseases where excess NO production is implicated.

CiteXplore: 16000003

DOI: 10.1021/jm050187a

Patent ID: ┄