Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Feb 1;27(3):578-581.
doi: 10.1016/j.bmcl.2016.12.014. Epub 2016 Dec 7.

Development of spiroguanidine-derived α7 neuronal nicotinic receptor partial agonists

Matthew D Hill  1 , Haiquan Fang  2 , Sivarao V Digavalli  2 , Francine L Healy  2 , Lizbeth Gallagher  2 , Debra Post-Munson  2 , Ping Chen  2 , Joanne Natale  2 , Yulia Benitex  2 , Daniel Morgan  2 , Nicholas Lodge  2 , Linda Bristow  2 , John E Macor  2 , Richard E Olson  2
Affiliations

Development of spiroguanidine-derived α7 neuronal nicotinic receptor partial agonists

Matthew D Hill et al. Bioorg Med Chem Lett. .

Abstract

We describe the synthesis of quinuclidine-containing spiroguanidines and their utility as α7 neuronal nicotinic acetylcholine receptor (nAChR) partial agonists. The convergent synthetic route developed for this study allowed for rapid SAR investigation and provided access to a structurally diverse set of analogs. A potent and selective α7 nAChR partial agonist, N-(6-methyl-1,3-benzoxazol-2-yl)-3',5'-dihydro-4-azaspiro[bicyclo[2.2.2]octane-2,4'-imidazole]-2'-amine (BMS-910731, 16), was identified. This compound induced immediate early genes c-fos and Arc in a preclinical rodent model of α7 nAChR-derived cellular activation and plasticity. Importantly, the ability to incorporate selectivity for the α7 nACh receptor over the 5-HT3A receptor in this series suggested a significant difference in steric requirements between the two receptors.

Keywords: 5-HT(3A) receptor; Immediate early genes; Schizophrenia; Spiroguanidine; α7 nicotinic acetylcholine receptor.

PubMed Disclaimer

MeSH terms

LinkOut - more resources