Development of novel anti-atheroscleroic agents

格列本脲是一种典型的抗糖尿病磺酰脲类药物，它对脂酰辅酶A：胆固醇酰基转移酶（ACAT）有抑制作用，而ACAT在细胞内游离胆固醇的降解和巨噬细胞泡沫细胞的形成中起着重要作用。本课题的目的是开发新型ACAT抑制剂，这些抑制剂在化学结构和性质上与传统的ACAT抑制剂不同，因为传统的化学中性药物候选人担心它们对肾上腺素的不良影响。在过去的三年里，我们组织了一个团队的生物有机化学家，合成有机化学家，分子药理学家和专业人员在药物的体内评价，并在计算机辅助药物设计。我们成功地创造了几种候选药物，它们消除了胰岛素分泌活性，并在选择性地递送到靶细胞和器官方面具有独特的ACAT抑制特性。目前化合物正在申请专利，专利申请完成后，我们将公开详细信息。

We have found that glibendamide, a typical antidiabetic sulfonylurea, inhibits acyl CoA:cholesterol acyllransferase (ACAT) that plays a crucial role to esterify the intracellular free cholesterol and a trigger to form foamed cells in macrophage. In this project we aim to develop novel ACAT inhibitors that are distinct from conventional ones in chemical structures and properties, because the conventional drug candidates of chemically neutral in charge are worried about their adverse effects on adrenal grand. During the passed three years, we organized a team of bioorganic chemist, synthetic organic chemist, molecular pharmacologist, and professionals in in vivo evaluation of drugs, and incomputer-aided drug design. We are succeeded in creating several drug candidates that are eliminated inslin secrition activity and have unique characteristics for ACAT inhibition in term of selective deliverly to taget cells and organs. The compounds are preparing for the patents and we will open the detailed information after the patent issue is completed.