Document Report Card

ID: ALA1121475

Journal: J Med Chem

Title: Inhibitors of indoleethylamine N-methyltransferase. Derivatives of 3-methyl-2-thiazolidinimine. In vitro, in vivo, and metabolic studies.

Authors: Rokach J, Girard Y, Hamel P, Reader G, Rooney CS, Mandel LR, Cragoe EJ, Zacchei AG.

Abstract: A variety of substituent groups has been attached to the exocyclic imine function of 2-imino-3-methylthiazolidine (1) in a search for metabolic precursors of this potent inhibitor of the enzyme indoleethylamine N-methyltransferase (INMT) which would exhibit superior pharmacodynamic properties in animals. It has been determined that chemically stable derivatives of 1 based on succinic, nicotinic, and N-acylated amino acids, although they lack in vitro efficacy, are potent inhibitors of INMT when administered orally or intravenously to rabbits. Metabolic studies carried out with 14C-labeled N,N'-bix(3-methyl-2-thiazolidinylidene)succinamide (3) have established that conversion of this compound to 1 occurs both in the whole rabbit and in the isolated rabbit liver. 1 itself has been shown to be metabolically inert in rabbits, being excreted primarily in the urine.

CiteXplore: 7401104

DOI: 10.1021/jm00181a014