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 journalArticle

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.

Original languageEnglish
Pages (from-to)2907-2912
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume8
Issue number20
DOIs
Publication statusPublished - Oct 20 1998

Fingerprint

Kynurenine 3-Monooxygenase
Kynurenine
Butyric Acid
Enantiomers
Structure-Activity Relationship
Tryptophan
Salts
Derivatives
Degradation
Enzymes
2-hydroxy-4-(3,4-dichlorophenyl)-4-oxobutanoic acid

Keywords

  • Enzyme inhibition
  • Hydroxylase
  • Kynurenine
  • Neuroprotection
  • Stereoselectivity

ASJC Scopus subject areas

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

Cite this

Giordani, A., Pevarello, P., Cini, M., Bormetti, R., Greco, F., Toma, S., ... Varasi, M. (1998). 4-phenyl-4-oxo-butanoic acid derivatives inhibitors of kynurenine 3- hydroxylase. Bioorganic and Medicinal Chemistry Letters, 8(20), 2907-2912. https://doi.org/10.1016/S0960-894X(98)00517-4

4-phenyl-4-oxo-butanoic acid derivatives inhibitors of kynurenine 3- hydroxylase. / Giordani, Antonio; Pevarello, Paolo; Cini, Massimo; Bormetti, Rita; Greco, Felicita; Toma, Salvatore; Speciale, Carmela; Varasi, Mario.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 8, No. 20, 20.10.1998, p. 2907-2912.

Research output: Contribution to journalArticle

Giordani, A, Pevarello, P, Cini, M, Bormetti, R, Greco, F, Toma, S, Speciale, C & Varasi, M 1998, '4-phenyl-4-oxo-butanoic acid derivatives inhibitors of kynurenine 3- hydroxylase', Bioorganic and Medicinal Chemistry Letters, vol. 8, no. 20, pp. 2907-2912. https://doi.org/10.1016/S0960-894X(98)00517-4
Giordani, Antonio ; Pevarello, Paolo ; Cini, Massimo ; Bormetti, Rita ; Greco, Felicita ; Toma, Salvatore ; Speciale, Carmela ; Varasi, Mario. / 4-phenyl-4-oxo-butanoic acid derivatives inhibitors of kynurenine 3- hydroxylase. In: Bioorganic and Medicinal Chemistry Letters. 1998 ; Vol. 8, No. 20. pp. 2907-2912.
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