iso-Lactam and reduced amide analogues of the peptidomimetic dopamine receptor modulator 3(R)-[(2(S)-Pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide

Kristine Dolbeare, Giuseppe F. Pontoriero, Suresh K. Gupta, Ram K. Mishra, Rodney L. Johnson

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

An analogue of the highly potent γ-lactam Pro-Leu-Gly-NH2 peptidomimetic, 3(R)-[(2(S)-pyrrolidinylcarbonyl) amino]-2-oxo-1-pyrrolidineacetamide (2), 4(R)-[[2(S)-pyrrolidinylcarbonyl]amino]-2-oxo-1-pyrrolidineacetamide (3), in which the lactam carbonyl moiety has been placed in a different position with respect to the 3-amino group was synthesized. Also, a series of analogues of 2, compounds 4-6, were synthesized in which each of the amide bonds of 2 were systematically replaced with a reduced amide bond surrogate. The analogues were tested for their ability to enhance the binding of [ 3H]N-propylnorapomorphine to dopamine receptors in a functional in vitro assay utilizing bovine striatal membranes. Peptidomimetic 3 was shown to be more potent than 2, while 4 and 5 were significantly less effective than 2. Peptidomimetic 6 had a pharmacological profile similar to that of 2.

Original languageEnglish (US)
Pages (from-to)4103-4112
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume11
Issue number18
DOIs
StatePublished - Sep 1 2003

Bibliographical note

Funding Information:
This work was supported in part by a NIH grant (NS20036) to R.L.J.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

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