[EN] BENZOPYRANE AND IMIDAZOLE DERIVATIVES USEFUL FOR THE STABILIZATION OF AMYLOIDOGENIC IMMUNOGLOBULIN LIGHT CHAINS<br/>[FR] DÉRIVÉS DE STABILISATION DE BENZOPYRANE ET D'IMIDAZOLE UTILISÉS POUR LA STABILISATION DE CHAÎNES LÉGÈRES D'IMMUNOGLOBULINES AMYLOÏDOGÉNIQUES
申请人:SCRIPPS RESEARCH INST
公开号:WO2020205683A1
公开(公告)日:2020-10-08
In immunoglobulin light chain amyloidosis (AL), the unique antibody light chain (LC) protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. For treating AL patients, such as those with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, provided herein are small molecule compounds of Formula Ia, Formula Ib, and Formula II that are kinetic stabilizers of the native dimeric structure of full-length LCs, which compounds can slow or stop the amyloidogenicity cascade at its origin.
在免疫球蛋白轻链淀粉样变性(AL)中,每位患者体内由单克隆浆细胞分泌的独特抗体轻链(LC)蛋白会错误折叠和/或聚集,导致器官退化的过程。为了治疗AL患者,例如那些存在严重心脏受累且难以耐受现有化疗方案的患者,本文提供了化学式Ia、化学式Ib和化学式II的小分子化合物,这些化合物是全长LC的动力学稳定剂,可以减缓或停止淀粉样生成性级联反应的起源。