Long‐acting dipeptidyl peptidase IV inhibitors have emerged as promising molecules for interventions for type 2 diabetes. Once weekly dosing brings greater patient compliance and more stable glycemic control. Starting from our previous highly potent compound with a thienoprimidine scaffold, which is unfortunately severely hit by hepatic biotransformation, a lead compound was rapidly generated by drawing on the experience of our previously discovered long‐acting compounds with pyrrolopyrimidine scaffold. With the aid of an in silico biotransformation prediction tool, (R)‐2‐((2‐(3‐aminopiperidin‐1‐yl)‐4‐oxo‐6‐(pyridin‐3‐yl)thieno[3,2‐d]pyrimidin‐3(4H)‐yl)methyl)‐4‐fluorobenzonitrile was eventually generated and determined to have high potency, a fine pharmacokinetic profile, and a long‐acting in vivo efficacy.

中文翻译：

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通过使用in silico生物转化预测工具进行基于特性的优化，发现了口服活性和长效DPP-IV抑制剂。

长效二肽基肽酶IV抑制剂已成为治疗2型糖尿病的有前途的分子。每周一次给药可提高患者依从性和更稳定的血糖控制。从我们以前的高效化合物-噻吩并吡啶骨架（不幸地受到肝脏生物转化的严重打击）开始，通过借鉴我们先前发现的具有吡咯并嘧啶骨架的长效化合物的经验，迅速生成了先导化合物。借助计算机生物转化预测工具，（R）-2-（（2-（3-氨基哌啶-1-基）-4-氧-6-（吡啶-3-基）噻吩并[3,2- d最终产生了]嘧啶-3（4H）-基）甲基）-4-氟苄腈，并确定具有较高的效价，良好的药代动力学特性和长效的体内功效。