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Updated: Jun 28, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Novel 2-imidazoles as potent, selective and CNS penetrant alpha1A adrenoceptor partial agonists
Lee R Roberts1, Justin Bryans, Kelly Conlon
1Department of Chemistry, Pfizer Global Research and Development, Sandwich Labs, IPC432, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. lee.roberts@pfizer.com
Abstract:
A novel series of central nervous system (CNS) penetrant indane 2-imidazoles have been identified as potent, partial agonists of the alpha(1A) adrenergic receptor, having good selectivity over the alpha(1B), alpha(1D) and alpha(2) sub-types. A key structural motif to impart selectivity is a methylene spacer between the indane and a pendant substituent, which includes heterocycles, sulphones and ethers. Introduction of an ortho-halogen to this group led to a lowering of intrinsic efficacy (E(max)).
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