MRTX1719 is an inhibitor of the PRMT5/MTA complex and recently entered clinical trials for the treatment of MTAP-deleted cancers. MRTX1719 is a class 3 atropisomeric compound that requires a chiral synthesis or a chiral separation step in its preparation. Here, we report the SAR and medicinal chemistry design strategy, supported by structural insights from X-ray crystallography, to discover a class 1 atropisomeric compound from the same series that does not require a chiral synthesis or a chiral separation step in its preparation.

中文翻译：

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设计和评估非手性、非阻转异构 4-(aminomethyl)phthalazin-1(2H)-one 衍生物作为新型 PRMT5/MTA 抑制剂

MRTX1719 是 PRMT5/MTA 复合物的抑制剂，最近进入了治疗 MTAP 缺失癌症的临床试验。MRTX1719是一种 3 类阻转异构化合物，在其制备过程中需要手性合成或手性分离步骤。在这里，我们报告了 SAR 和药物化学设计策略，在 X 射线晶体学的结构洞察力的支持下，从同一系列中发现了一种在其制备过程中不需要手性合成或手性分离步骤的 1 类阻转异构化合物。