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Design, synthesis, and structure-activity relationships of indole-3-heterocycles as agonists of the CB1 receptor.

Authors :
Morrison AJ
Adam JM
Baker JA
Campbell RA
Clark JK
Cottney JE
Deehan M
Easson AM
Fields R
Francis S
Jeremiah F
Keddie N
Kiyoi T
McArthur DR
Meyer K
Ratcliffe PD
Schulz J
Wishart G
Yoshiizumi K
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 Jan 01; Vol. 21 (1), pp. 506-9. Date of Electronic Publication: 2010 Oct 25.
Publication Year :
2011

Abstract

Novel indole-3-heterocycles were designed and synthesized and found to be potent CB1 receptor agonists. Starting from a microsomally unstable lead 1, a bioisostere approach replacing a piperazine amide was undertaken. This was found to be a good strategy for improving stability both in vitro and in vivo. This led to the discovery of 24, which had an increased duration of action in the mouse tail flick test in comparison to the lead 1.<br /> (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
21
Issue :
1
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
21075630
Full Text :
https://doi.org/10.1016/j.bmcl.2010.10.093