Selective synthesis and utility of one tripyrrolic compound and its intermediates.

Highly selective syntheses of tri(2,4-dimethyl-3-carbethoxypyrrolyl)-methane 8 and its dipyrrolic intermediate 6 and pyrrolic one 1 are described based on the successful correction of the wrong process for 1 in literature. Tripyrrolic compounds have attracted much attention recently and been developed in diverse fields. 1 was the key intermediate for some tyrosine kinase inhibitors, including newly-launched Sutent, and most recently we have found 6 was also synthetically useful in the synthesis of 11 that has been discovered as a novel histone deacetylases (HDAC) inhibitor with an IC(50) value of about 1 microM in our assessments and represents a promising lead for the development of more potent histone deacetylase inhibitors (HDACIs).

基于对文献中化合物1错误合成过程的成功纠正，本文描述了三（2,4 - 二甲基 - 3 - 乙酯基吡咯基）甲烷8及其二吡咯中间体6和吡咯化合物1的高选择性合成。三吡咯化合物最近备受关注，并在多个领域得到了发展。化合物1是一些酪氨酸激酶抑制剂（包括新上市的索坦）的关键中间体，并且我们最近发现化合物6在合成11时也具有合成用途，在我们的评估中，11被发现是一种新型的组蛋白去乙酰化酶（HDAC）抑制剂，其IC₅₀值约为1μM，是开发更有效的组蛋白去乙酰化酶抑制剂（HDACIs）的一个有前景的先导化合物。