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. Epub 2008 Oct 19.

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)).

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists*
  • Amino Acid Motifs
  • Central Nervous System / drug effects*
  • Chemistry, Pharmaceutical / methods*
  • Chromatography, High Pressure Liquid
  • Drug Design
  • Halogens / chemistry
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology*
  • Kinetics
  • Microsomes, Liver / drug effects
  • Models, Chemical
  • Structure-Activity Relationship
  • Sulfonamides / chemistry

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Halogens
  • Imidazoles
  • Sulfonamides