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

A novel series of central nervous system (CNS) penetrant indane 2-imidazoles have been identified as potent, partial agonists of the α1A adrenergic receptor, having good selectivity over the α1B, α1D and α2 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 (Emax).

Graphical abstractA series of novel 2-imidazoles is described, which combine potent and selective α1A partial agonist pharmacology with good CNS penetration.Figure optionsDownload full-size imageDownload as PowerPoint slide