申请人长期从事药物设计与发现研究，尤其在磷酸二酯酶PDE高选择性抑制剂发现领域取得较大突破：①发展了两项药物设计新技术；②设计和优化了嘧啶酮类PDE9抑制剂，发现得到目前选择性最高的先导物28s（JMC2012）和活性最强的3r（JMC2014,选择性/活性明显优于辉瑞二期临床药物,被F1000重点推荐），后发展得到了抗AD临床前候选药物LW33，已进入临床前研究；与西地那非相比，发现了骨架新颖且选择性更高的吡咯色原酮类PDE5抑制剂5r；并揭示这两个靶标中主导抑制剂选择性的结构要素(分子机制)；③从中药卷柏中发现具有全新骨架结构、nM级抗哮喘PDE4选择性抑制剂JB20。近五年发表SCI论文48篇，他引527次，其中通讯作者28篇第一作者2篇；申请7项发明专利和2项PCT。入选中国药学会施维雅青年药物化学奖。本项目在已有基础上，拟开展抗AD高选择性创新先导结构的系统发现、优化和机制研究。

My research interests mainly focus on drug design and discovery, especially made great breakthrough in the field of discovery of highly selective inhibitor against Phosphodiesterase (PDE): 1) development of two new drug design technologies; 2) with the combination of structural biology methods, design and optimize PDE9 inhibitors, found at the highest selectivity and the strongest inhibitory effect of the lead structures 28s （JMC 2012）and 3r (JMC2014, whose selectivity and inhibitory effect are obviously superior to Pfizer phase two clinical drug). Based on 28s and 3r, an anti-AD preclinical drug candidate LW33 is entering the preclinical studies. Compared with the control drug sildenafil, a novel structure framework but higher selectivity of pyrrole chromones PDE5 inhibitor 5r was discovered. Both studies reveal the molecular mechanism of PDE9 and PDE5 highly selective inhibitors; 3) discover an anti-asthma PDE4 selective inhibitor JB20 at nM level from Chinese traditional medicine Selaginella tamariscina. Since 2010, I have published 48 SCI papers, which have been cited for 517 times. In 28 articles (such as J Med Chem and Chem Commun ) and 2 papers, I worked as the corresponding and first authors, respectively. I have applied two PCT and seven invention patents. I have won the CPA-Servier Young Investigator Awards in Medicinal Chemistry. Based on previous work in this project, studies on the design, optimization, and mechanism for anti-AD agents with high selectivity will be performed.