The discovery of biaryl carboxamides as novel small molecule agonists of the motilin receptor.

作者信息

Westaway Susan M, Brown Samantha L, Conway Elizabeth, Heightman Tom D, Johnson Christopher N, Lapsley Kate, Macdonald Gregor J, MacPherson David T, Mitchell Darren J, Myatt James W, Seal Jon T, Stanway Steven J, Stemp Geoffrey, Thompson Mervyn, Celestini Paolo, Colombo Andrea, Consonni Alessandra, Gagliardi Stefania, Riccaboni Mauro, Ronzoni Silvano, Briggs Michael A, Matthews Kim L, Stevens Alexander J, Bolton Victoria J, Boyfield Izzy, Jarvie Emma M, Stratton Sharon C, Sanger Gareth J

机构信息

Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK.

出版信息

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6429-36. doi: 10.1016/j.bmcl.2008.10.072. Epub 2008 Oct 19.

DOI:10.1016/j.bmcl.2008.10.072

PMID:19006669

Abstract

Optimisation of urea (5), identified from high throughput screening and subsequent array chemistry, has resulted in the identification of pyridine carboxamide (33) which is a potent motilin receptor agonist possessing favourable physicochemical and ADME profiles. Compound (33) has demonstrated prokinetic-like activity both in vitro and in vivo in the rabbit and therefore represents a promising novel small molecule motilin receptor agonist for further evaluation as a gastroprokinetic agent.

摘要

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