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Continued optimization of the MLPCN probe ML071 into highly potent agonists of the hM1 muscarinic acetylcholine receptor.

Authors :
Melancon BJ
Gogliotti RD
Tarr JC
Saleh SA
Chauder BA
Lebois EP
Cho HP
Utley TJ
Sheffler DJ
Bridges TM
Morrison RD
Daniels JS
Niswender CM
Conn PJ
Lindsley CW
Wood MR
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 May 15; Vol. 22 (10), pp. 3467-72. Date of Electronic Publication: 2012 Mar 29.
Publication Year :
2012

Abstract

This Letter describes the continued optimization of the MLPCN probe molecule ML071. After introducing numerous cyclic constraints and novel substitutions throughout the parent structure, we produced a number of more highly potent agonists of the M(1) mACh receptor. While many novel agonists demonstrated a promising ability to increase soluble APPĪ± release, further characterization indicated they may be functioning as bitopic agonists. These results and the implications of a bitopic mode of action are presented.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
22
Issue :
10
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
22507963
Full Text :
https://doi.org/10.1016/j.bmcl.2012.03.088