Novel 2-imidazoles as potent, selective and CNS penetrant α1A adrenoceptor partial agonists

Abstract A novel series of central nervous system (CNS) penetrant indane 2-imidazoles have been identified as potent, partial agonists of the α 1A adrenergic receptor, having good selectivity over the α 1B , α 1D and α 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 ).