Development of novel anti-atheroscleroic agents

我们发现格列苯达胺是一种典型的抗糖尿病磺脲类药物，可抑制酰基辅酶a：胆固醇酰基转移酶（ACAT），而ACAT在巨噬细胞中对细胞内游离胆固醇的酯化和泡沫细胞的形成起着至关重要的作用。在本项目中，我们的目标是开发在化学结构和性质上与传统药物不同的新型ACAT抑制剂，因为化学中性的传统候选药物担心它们对肾上腺的不良影响。在过去的三年里，我们组织了一支由生物有机化学家、合成有机化学家、分子药理学家和药物体内评价、计算机辅助药物设计等专业人员组成的团队。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，并且在选择性递送到靶细胞和器官方面具有独特的ACAT抑制特性。化合物正在准备申请专利，我们将在专利申请完成后公开详细信息。

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.