合成与评价 1,4-二苯基丁二烯衍生物作为纤溶酶原激活物抑制剂-1（PAI-1）产生抑制剂。
Synthesis and evaluation of 1,4-diphenylbutadiene derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1) production.
机构信息
Medicinal Chemistry Laboratory, Mitsubishi Tanabe Pharma Co., Ltd, 3-16-89, Kashima, Yodogawa, Osaka 532-8505, Japan.
出版信息
Bioorg Med Chem. 2010 Mar 1;18(5):1968-79. doi: 10.1016/j.bmc.2010.01.032. Epub 2010 Jan 18.
Butadiene-imide 1 (T-686) derivatives were synthesized and evaluated for their inhibitory activity against PAI-1 production and their ADMET (DMPK and toxicology) profiles. Among these derivatives, compound 15k (T-2639) showed good antithrombotic activity in two rat thrombosis models without affecting bleeding time, indicating reduction of haemorrhagic risk. We also describe in this report a practical synthesis of 15k suitable for scale-up using Z,E-selective Stobbe condensation.
丁二烯亚胺 1（T-686）衍生物被合成并评估其对 PAI-1 产生的抑制活性及其 ADMET（DMPK 和毒理学）特征。在这些衍生物中，化合物 15k（T-2639）在两种大鼠血栓模型中表现出良好的抗血栓活性，而不影响出血时间，表明出血风险降低。我们还在本报告中描述了一种使用 Z，E-选择性 Stobbe 缩合适用于放大的 15k 的实用合成方法。
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