SAR studies of piperidine-based analogues of cocaine. Part 3: Oxadiazoles

Pavel A. Petukhov, Mei Zhang, Kenneth J. Johnson, Srihari R. Tella, Alan P. Kozikowski

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The synthesis of novel 4β-aryl-1-methyl-3α-(3-substituted-1,2,4-oxadiazol-5-yl) piperidines, bioisosteres of ester (+)-1, is described. The synthesized oxadiazoles were evaluated for their affinity to the DAT and their ability to inhibit monoamine reuptake at the DAT, NET, and 5HTT. The results show that affinity to the DAT and ability to inhibit the reuptake at the DAT, NET, and 5HTT is a function of the size of the substituent in the oxadiazole ring. (+)-(3R,4S)-4β-(4-Chlorophenyl)-1-methyl-3α-(3-methyl-1,2,4- oxadiazol-5-yl)piperidine [(+)-2a], which is structurally and pharmacologically most similar to the ester (+)-1 in this series, showed at least a 2-fold longer duration of action when compared to ester (+)-1.

Original languageEnglish (US)
Pages (from-to)2079-2083
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume11
Issue number16
DOIs
StatePublished - Aug 20 2001

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'SAR studies of piperidine-based analogues of cocaine. Part 3: Oxadiazoles'. Together they form a unique fingerprint.

  • Cite this

    Petukhov, P. A., Zhang, M., Johnson, K. J., Tella, S. R., & Kozikowski, A. P. (2001). SAR studies of piperidine-based analogues of cocaine. Part 3: Oxadiazoles. Bioorganic and Medicinal Chemistry Letters, 11(16), 2079-2083. https://doi.org/10.1016/S0960-894X(01)00379-1