4-phenyl-4-oxo-butanoic acid derivatives inhibitors of kynurenine 3- hydroxylase

Antonio Giordani, Paolo Pevarello, Massimo Cini, Rita Bormetti, Felicita Greco, Salvatore Toma, Carmela Speciale, Mario Varasi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2907-2912
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Issue number20
Publication statusPublished - Oct 20 1998


  • Enzyme inhibition
  • Hydroxylase
  • Kynurenine
  • Neuroprotection
  • Stereoselectivity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science


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