II. Discovery of a novel series of CXCR3 antagonists with a beta amino acid core

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• 作者：Imre Bata ; ^&dagger ; ; ^{batai@richter.hu" class="auth_mail" title="E-mail the corresponding author} ; Zsuzsanna Tö ; mö ; skö ; zi ; Pé ; ter Buzder-Lantos ; Attila Vasas^&Dagger ; ; Gá ; bor Szeleczky ; Lá ; szló ; Balá ; zs ; Veronika Barta-Bodor ; Gyö ; rgy G. Ferenczy ; ^§ ; ; ^{ferenczy.gyorgy@med.semmelweis-univ.hu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：QFOOZQUUYROMBF-QFIPXVFZSA-N ; LJWSTVOVBMILMB-VWLOTQADSA-N ; GZIJLFNNAVWXNH-QFIPXVFZSA-N
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：26
• 期：22
• 页码：5429-5437
• 全文大小：2919 K

文摘

A new series of beta amino acids, which act as CXCR3 antagonists, has been identified. The formerly optimized N,N-disubstituted benzylamine derivatives with carboxylic acid function on the N-atom was used as starting point and compounds with carboxyl function not attached to the N-atom were investigated. Affinity, metabolic stability in human and mouse liver microsomes and Caco-2 permeability were optimized. Compounds with double-digit nanomolar CXCR3 affinity, favourable microsomal stability and Caco-2 permeability have been identified.