Research and Development, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, United States.
Research and Development, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, United States.
Bioorg Med Chem Lett. 2022 Sep 15;72:128843. doi: 10.1016/j.bmcl.2022.128843. Epub 2022 Jun 7.
Cystic fibrosis (CF) is an autosomal recessive disease resulting from mutations on both copies of the CFTR gene. Phenylalanine deletion at position 508 of the CFTR protein (F508del-CFTR) is the most frequent mutation in CF patients. Currently, the most effective treatments of CF use a dual or triple combination of CFTR correctors and potentiators. In triple therapy, two correctors (C1 and C2) and a potentiator are employed. Herein, we describe the identification and exploration of the SAR of a series of 4-aminopyrrolidine-2-carboxylic acid C2 correctors of CFTR to be used in conjunction with our existing C1 corrector series for the treatment of CF.
囊性纤维化（CF）是一种常染色体隐性疾病，由 CFTR 基因的两个拷贝上的突变引起。CFTR 蛋白第 508 位苯丙氨酸缺失（F508del-CFTR）是 CF 患者中最常见的突变。目前，CF 的最有效治疗方法是使用 CFTR 校正剂和增效剂的双重或三重组合。在三重疗法中，使用两种校正剂（C1 和 C2）和一种增效剂。在此，我们描述了一系列 4-氨基吡咯烷-2-羧酸 CFTR C2 校正剂的鉴定和 SAR 研究，这些校正剂将与我们现有的 C1 校正剂系列一起用于 CF 的治疗。
