Discovery Chemistry, Pfizer Global Research and Development, Sandwich, United Kingdom.
Bioorg Med Chem Lett. 2010 Jan 15;20(2):516-20. doi: 10.1016/j.bmcl.2009.11.097. Epub 2009 Nov 23.
A series of aryloxyazetidines, aryloxypyrrolidines and aryloxypiperidines were designed based on structural overlap with previously reported arylpyrazine Oxytocin antagonists. Similarly high levels of Oxytocin antagonism were achievable in these new series. Several aryloxyazetidines also showed high levels of selectivity, with one compound, 25, displaying promising in vivo pharmacokinetics and significantly improved aqueous solubility over related compounds containing a biaryl substituent.
基于与先前报道的芳基吡嗪催产素拮抗剂的结构重叠，设计了一系列芳氧基氮杂环丁烷、芳氧基吡咯烷和芳氧基哌啶。在这些新系列中，同样可以达到类似高水平的催产素拮抗作用。几种芳氧基氮杂环丁烷也表现出较高的选择性，其中一种化合物 25 具有良好的体内药代动力学特性，并且与含有联苯取代基的相关化合物相比，显著提高了水溶解度。
