The discovery of the benzazepine class of histamine H3 receptor antagonists

Abstract

This Letter describes the discovery of a novel series of H3 receptor antagonists. The initial medicinal chemistry strategy focused on deconstructing and simplifying an early screening hit which rapidly led to the discovery of a novel series of H3 receptor antagonists based on the benzazepine core. Employing an H3 driven pharmacodynamic model, the series was then further optimised through to a lead compound that showed robust in vivo functional activity and possessed overall excellent developability properties.

Keywords: Alzheimer’s disease; Benzazepine; GPCR; H(3) receptor antagonist; Histamine; Neurotransmitters.