Conformational analysis of two inhibitors of prolyl-endopeptidase: Comparison of 4-phenyl-butyryl- and octanoyl-prolyl-pyrrolidine

Miklós Fehér, Károly Kánai, Benjámin Podányi, István Hermecz

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The conformational analysis of two prolyl-endopeptidase (PEP) inhibitors was performed. A molecular mechanics based random conformational search showed that 4-phenyl-butyryl-prolyl-pyrrolidine is U-shaped in most low-energy conformations. The results were compared with semiempirical AM1 calculations. In contrast, the molecule octanoyl-prolyl-pyrrolidine has a linear alkyl-chain, although the U-shaped conformations, required for the same mechanism of action, can be easily attained. The results of conformational analyses were compared with those of NMR measurements. The common pharmacophore for these and several other PEP inhibitors was derived.

Original languageEnglish
Pages (from-to)136-141
Number of pages6
JournalQuantitative Structure-Activity Relationships
Volume16
Issue number2
DOIs
Publication statusPublished - Apr 1997

Keywords

  • 3D-QSAR
  • 4-phenyl-butyryl-prolyl-pyrolidine
  • Conformational search
  • NMR
  • Octanoyl-prolyl-pyrolidine
  • PEP inhibitors
  • Pharmacophore
  • Propyl-endopeptidase inhibitors

ASJC Scopus subject areas

  • Pharmacology

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