138449-25-9Relevant academic research and scientific papers
Modification of the potent peptide FK888 with unusual aminoacids: Effects on activity on neurokinin receptors
Caliendo,Greco,Grieco,Perissutti,Santagada,Calignano,Mancuso,Novellino
, p. 197 - 201 (2007/10/03)
We report on the synthesis and the pharmacological properties of a new series of tachykinin antagonists based on the peptide N2-[(4R)-4-hydroxy-1-[(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl]-N-m ethyl-N-(phe-nylmethyl)-3-(2-naphthyl)-L-alaninamide (FK888) modified on the (2-naphthyl)-L-alanine and the [(1-methyl-1H-indol-3-yl)carbonyl] moieties. The compounds were tested on guinea pig ileum for NK-1, rat colon for NK-2 and rat portal vein for NK-3 receptors. The two most potent peptides of this series, 1b and 2d, were selective for the NK-2 receptor (pA2 = 7.5 and 7.3, respectively).
Studies of Neurokinin Antagonists. 4. Synthesis and Structure-Activity Relationships of Novel Dipeptide Substance P Antagonists: N2--L-prolyl>-N-methyl-N-(phenylmethyl)-3-(2-naphthyl)-L-alaninamide and Its Related Compounds
Hagiwara, Daijiro,Miyake, Hiroshi,Igari, Norihiro,Karino, Masako,Maeda, Yasue,et al.
, p. 2090 - 2099 (2007/10/02)
As an extension of our studies on discovering a novel substance P (SP) antagonist, we modified the previously reported dipeptide, N2-2-(1H-indol-3-ylcarbonyl)-L-lysyl>-N-methyl-N-(phenylmethyl)-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 SP binding assay using guinea pig lung membranes.Next we modified the 1H-indol-3-ylcarbonyl part in 3h.Introduction of a methyl group at the indole nitrogen enhanced the oral activity, while retaining the binding activity.Finally, we modified the phenylalanine part to culminate in the most potent compound 7k (FK888), which is a potent SP antagonist with NK1 selectivity as well as oral activity.
