Studies on neurokinin antagonists. 4. Synthesis and structure-activity relationships of novel dipeptide substance P antagonists: N2-[(4R)-4-hydroxy-1-[(1-methyl-1H- …

D Hagiwara, H Miyake, N Igari, M Karino…

Index: Hagiwara, Daijiro; Miyake, Hiroshi; Igari, Norihiro; Karino, Masako; Maeda, Yasue; et al. Journal of Medicinal Chemistry, 1994 , vol. 37, # 13 p. 2090 - 2099

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Citation Number: 18

Abstract

As an extension of our studies on discovering a novel substance P (SP) antagonist, we modified the previously reported dipeptide, W-[W-(1H-indol-3-ylcarbony1)-~-lysyll-N-methyl- N-(phenyl-methyl)-L-phenylalaninamide (2b). The lysine part in 2b was first optimized to a (2S, 4R)-hydroxyproline derivative (3h), which is 2-fold more potent than 2b in [3HlSP binding assay using guinea pig lung membranes. Next we modified the lH-indol-3- ...