4-Phenyl-4-oxo-butanoic acid derivatives inhibitors of kynurenine 3-hydroxylase.

Basic Information

ID: ALA1130635

Journal: Bioorg Med Chem Lett

Title: 4-Phenyl-4-oxo-butanoic acid derivatives inhibitors of kynurenine 3-hydroxylase.

Authors: Giordani A, Pevarello P, Cini M, Bormetti R, Greco F, Toma S, Speciale C, Varasi M.

Abstract: Kynurenine 3-hydroxylase (KYN 3-OHase) is a key enzyme in the kynurenine pathway of tryptophan degradation and its inhibition may be an effective mechanism for counteracting neuronal excitotoxic damage. We present here a new class of inhibitors derived from a structure-activity relationship (SAR) study of the benzoylalanine side-chain of 1. 2-hydroxy-4-(3,4-dichlorophenyl)-4-oxobutanoic acid (8) and 2-benzyl-4-(3,4-dichlorophenyl)-4-oxo-butanoic acid (10) emerged as the most interesting derivatives. Enantiospecific synthesis for both enantiomers of 8 and diastereomeric salt resolution for those of 10 were successfully applied.

CiteXplore: 9873646

DOI: 10.1016/s0960-894x(98)00517-4

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