2. Academic Validation
  3. Novel 2-imidazoles as potent, selective and CNS penetrant alpha1A adrenoceptor partial agonists

Novel 2-imidazoles as potent, selective and CNS penetrant alpha1A adrenoceptor partial agonists

  • Bioorg Med Chem Lett. 2008 Dec 15;18(24):6437-40. doi: 10.1016/j.bmcl.2008.10.066.
Lee R Roberts 1,  Justin Bryans,  Kelly Conlon,  Gordon McMurray,  Alan Stobie,  Gavin A Whitlock
Affiliations

Affiliation

  • 1 Department of Chemistry, Pfizer Global Research and Development, Sandwich Labs, IPC432, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. lee.roberts@pfizer.com
PMID: 18980842 DOI: 10.1016/j.bmcl.2008.10.066
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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