Synthesis and affinity studies of himbacine derived muscarinic receptor antagonists

Ling-Jie Gao; Magali Waelbroeck; Sven Hofman; Dirk Van Haver; Marco Milanesio; Davide Viterbo; Pierre J De Clercq

doi:10.1016/s0960-894x(02)00315-3

Synthesis and affinity studies of himbacine derived muscarinic receptor antagonists

Bioorg Med Chem Lett. 2002 Aug 5;12(15):1909-12. doi: 10.1016/s0960-894x(02)00315-3.

Authors

Ling-Jie Gao¹, Magali Waelbroeck, Sven Hofman, Dirk Van Haver, Marco Milanesio, Davide Viterbo, Pierre J De Clercq

Affiliation

¹ Department of Organic Chemistry, Ghent University, Krijgslaan 281, Belgium.

PMID: 12113806
DOI: 10.1016/s0960-894x(02)00315-3

Abstract

A series of himbacine (1)-related analogues has been prepared featuring three different isomeric configurations with respect to the B-ring (a, b and natural c) and three different interconnecting two-carbon unsaturated units [natural (E)-ene, (Z)-ene, and yne]. The study of the binding affinities of the nine resulting compounds, including synthetic (+)-himbacine (3c), towards the M(1)-M(4) muscarine receptor subtypes revealed that analogues 3a and 5c display a promising 10-fold selectivity for the M(2) receptor as compared to the M(1) receptor.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Alkaloids / chemistry*
Alkaloids / pharmacology*
Animals
Binding, Competitive
CHO Cells / metabolism
Cricetinae
Furans
Humans
Muscarinic Antagonists / chemical synthesis*
Muscarinic Antagonists / pharmacology*
Naphthalenes
Piperidines
Protein Binding
Receptors, Muscarinic / metabolism
Stereoisomerism
Structure-Activity Relationship
Substrate Specificity

Substances

Alkaloids
Furans
Muscarinic Antagonists
Naphthalenes
Piperidines
Receptors, Muscarinic
himbacine