130406-44-9Relevant academic research and scientific papers
Rationally designed 'dipeptoid' analogues of cholecystokinin (CCK): N-terminal structure-affinity relationships of α-methyl-tryptophan derivatives
Eden,Higginbottom,Hill,Horwell,Hunter,Martin,Pritchard,Rahman,Richardson,Roberts
, p. 37 - 45 (2007/10/02)
The structure-affinity relationships (SAR) between the N-terminii of a series of α-methyl-tryptophanylphenethylamide derivatives and the cholecystokinin (CCK) B receptor are discussed. A series of compounds with the general formula R-X-α-methyl-tryptophanylphenethylamide was prepared, where R is a cycloalkyl, a bicycloalkyl or a tricycloalkyl group and X is a urethane, thiourethane, amide, urea or a sulphinamide linking group. The CCK-B receptor binding affinities of these are discussed. The SAR form part of a systematic program for the rational design of 'dipeptoid' analogues of the neuropeptide CCK. Beginning with 1,1-dimethylpropyl (±)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2- [(2-phenylethyl)amino carbamate (IC50 = 4720 nM on CCK-B binding affinity) the N-terminal moiety was systematically changed for groups of varying size, shape and lipophilicity until the optimal N-terminal group was obtained and the favoured linking group chosen, resulting in the compound tricyclo[3.3.1.13,7)]dec-2-yl(R)-[(1H-indol-3-ylmethyl)-1-methyl- 2-oxo-2[(2-phenylethyl)amino]ethyl]carbamate with and IC50 = 32 nM on CCK-B receptor binding affinity.
Rationally Designed "Dipeptoid" Analogues of CCK. α-Methyltryptophan Derivatives as Highly Selective and Orally Active Gastrin and CCK-B Antagonists with Potent Anxiolytic Properties
Horwell, David C.,Hughes, John,Hunter, John C.,Pritchard, Martyn C.,Richardson, Reginald S.,at al.
, p. 404 - 414 (2007/10/02)
This paper describes the synthesis and structure-activity relationships (SAR) leading to the first rational design of "dipeptoid" analogues of the neuropeptide cholecystokinin (CCK).Compounds *,S*)>-4-2-3-(1H-indol-3-yl)-2-m
