Conformationally constrained tachykinin analogs: potent and highly selective neurokinin NK-2 receptor agonists

…, SJ Ireland, CC Jordan, AB McElroy…

Index: Deal, Martyn J.; Hagan, Russell M.; Ireland, Simon J.; Jordan, Christopher C.; McElroy, Andrew B.; et al. Journal of Medicinal Chemistry, 1992 , vol. 35, # 22 p. 4195 - 4204

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Citation Number: 34

Abstract

The design and synthesis of potent and selective neurokinin NK-2 receptor agonists 12 (GR64349) and 31 are described, together with structureactivity relationships for related analogues. Compound 12 (E&= 3.7 nM at NK-2 receptors in the rat colon; selectivity> low- and> 300-fold with respect to NK-1 and NK-3 receptors, respectively) was derived by incorporation of a Gly-Leu y-lactam conformational constraint into the C-terminal region of ...