Hanessian Stephen, Jennequin Thomas, Boyer Nicolas, Babonneau Vincent, Soma Udaykumar, Mannoury la Cour Clotilde, Millan Mark J, De Nanteuil Guillaume
Department of Chemistry, Université de Montréal , Station Centre-Ville, Montréal, Que. H3C 3J7, Canada.
Department of Psychopharmacology, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, France.
ACS Med Chem Lett. 2014 Feb 13;5(5):550-5. doi: 10.1021/ml400528y. eCollection 2014 May 8.
In connection with a program directed at potent and balanced dual NK1/NK3 receptor ligands, a focused exploration of an original class of peptidomimetic derivatives was performed. The rational design and molecular hybridization of a novel phenylalanine core series was achieved to maximize the in vitro affinity and antagonism at both human NK1 and NK3 receptors. This study led to the identification of a new potent dual NK1/NK3 antagonist with pK i values of 8.6 and 8.1, respectively.
针对高效且平衡的双NK1/NK3受体配体的项目,对一类原始的拟肽衍生物进行了重点研究。通过合理设计和分子杂交,构建了一个新型苯丙氨酸核心系列,以最大化其对人NK1和NK3受体的体外亲和力和拮抗作用。该研究鉴定出一种新的强效双NK1/NK3拮抗剂,其pKi值分别为8.6和8.1。