“精准化学”在药物发现中的应用

doi:10.6023/cjoc202505031

综述与进展

“精准化学”在药物发现中的应用

刘荣^a, 左应林^*a,b,c, 张英俊^*a,b,c, 张霁^*a,b,c

^a广东东阳光药业股份有限公司东莞 523871
^b抗感染新药研发全国重点实验室东莞 523871
^c广东省抗病毒药物研发企业重点实验室东莞 523871

收稿日期:2025-05-30 修回日期:2025-08-06
作者简介:刘荣, 2022年毕业于四川大学化学学院有机化学专业,获博士学位,以第一或第二作者在Org. Lett., Chem. Commun., Tetrahedron, Toxicol. Appl. Pharmacol., Pharmacol. Res.等国际知名期刊发表SCI论文5篇,申请专利8项且8项已经获得授权; 2024 年加入广东东阳光药业股份有限公司,从事抗感染药物研发;
左应林,博士,2012年中山大学药物化学专业博士毕业,随后加入东阳光研究院,从事一类新药研发工作, 先后担任心血管原创部副部长、计算化学部部长、代谢组药化总监、抗感染组药化总监、抗感染新药研发全国重点实验室首席研究员和抗感染新药研发全国重点实验室管理委员会委员等职务,负责公司多个1类新药项目研发,作为主要研究者和项目负责人主导以下临床项目：治疗慢性肾脏病相关的贫血1类新药、治疗肺动脉高压/慢性血栓栓塞性肺高血压1类新药、治疗慢性心力衰竭1类新药、治疗非髓系恶性肿瘤受试者化疗引起的贫血1类新药、治疗糖尿病肾脏病1类新药; 目前有多个临床前小核酸和小分子项目在研; 获公司新药之星,科技进步一等奖,总公司级劳模等表彰; 曾参与1项国家863项目,2项国家自然科学基金项目; 在J. Med. Chem., Biochem.Pharmacol., Eur. J. Med. Chem., Mol. Cancer. Ther.等国际知名杂志发表SCI论文13篇; 目前已申请专利219项,其中68项已授权; 担任广东省药学会药物化学专业委员会委员;
张英俊,广东东阳光药业股份有限公司董事长,药业研究院院长; 国务院特殊津贴专家,国家中青年科技创新领军人才,抗感染新药研发全国重点实验室常务副主任和学术委员会委员,全国药学会药物化学专业委员会委员,国家知识产权局中国专利审查技术专家,广东省药物化学委员会主任委员,曾担任国家“重大新药创制”科技重大专项负责人; 2007年获湖南大学有机化学博士学位,随后在日本冈山理科大学从事博士后研究; 2008年加盟东阳光,主要从事原创新药的研发,2009年带领团队完成对流感用药“达菲”的工艺改造,顺利完成国家下达的2亿片储备药的任务,为国家抗击禽流感做出了应有的贡献,为此团队获得了国家发改委表扬信的表彰; 近年来先后主持50多个1类创新药物研究,具有超16年的药物研发和管理经验,在感染、慢病、肿瘤领域疾病具有较深造诣,作为专利第一发明人带领团队成功上市了国产首个自主原研的抗丙肝新药东卫恩; 共推动3个创新药上市,1个创新药申请上市,10个全新分子处于临床II、III期研究,3个完成海外临床,打造了极具竞争力的原创新药产品线; 作为主要负责人承担多项国家“重大新药创制”重大科技专项课题和省市级科研项目; 迄今已在国内外重要学术刊物发表论文40多篇,并受邀撰写专著《Innovative Drug Synthesis》（Wiley, 2016）,担任多家国内知名刊物编委; 在新分子创新药治疗领域,申请发明专利1200余项,其中PCT专利136项,700多项获得授权,其中作为第一发明人已获230余项发明专利;
张霁,国家特聘专家,东阳光研究院药学首席科学家; 抗感染新药研发全国重点实验室学术委员会委员, 中国化学会工艺化学专委会委员, 同时兼任《中国医药工业杂志》副主编、《Pharmaceutical Fronts》副主任编委、《药学进展》编委, 曾担任国家“重大新药创制”科技重大专项负责人,广东省创新团队核心成员; 1987年获北京师范大学有机化学硕士学位并留校任教,1997 获加拿大维多利亚大学博士学位; 1997-2000 年在美国雅培任新药研发科学家,先后从事肿瘤,关节炎等新药的研发工作,由于药物研发工作取得重大成果, 2000 年获雅培CEO主席奖; 2000-2007 任美国辉瑞研发中心实验室高级研究员,博士后导师,药物研发项目总监,致力于抗肿瘤、抗病毒、中枢神经系统和心脑血管疾病等多种药物的研究及开发; 2007-2011 年任美国百时美施贵宝制药首席科学家,药物研发主管; 在三大跨国药业工作期间和加盟东阳光药业后, 先后领导并参与数十个新药、改良性新药的研究和开发工作; 推动新药获批上市的药物合成与工艺技术发展以及数个临床阶段及研发早期候选药物的化学合成与方法学/工艺研究及绿色化学的应用; 著作包括《Modern Drug Synthesis》（Wiley, 2010）,《Innovative Drug Synthesis》（Wiley, 2016）,《Current Drug Synthesis 》（Wiley, 2022）及《Chemistry and Pharmacology of Drug Discovery》（Wiley, 2024）; 发表研究论文近60篇及获得数十项授权专利, 同时担任中山大学药学院研究生导师、浙江大学博士生校外导师。
基金资助:
抗感染新药研发全国重点实验室(No.2015DQ780357),广东省抗病毒药物研发企业重点实验室(GrantNo.2020B1212070003),广东省抗病毒药物研发企业重点实验室(No.2023B1212070004)资助项目.

Emerging Applications of Precise Chemistry in Drug Discovery

Rong Liu^a, Yinglin Zuo^*,a,b,c, Yingjun Zhang^*,a,b,c, Ji Zhang^*,a,b,c

^aSunshine Lake Pharma Co.,Ltd, Dongguan 523871
^bState Key Laboratory of Anti-Infective Drug Development, Sunshine Lake Pharma Co.,Ltd, Dongguan 523871
^cEnterprise Key Laboratory of Anti-viral Drug Development for Guangdong Province, Dongguan 523871

Received:2025-05-30 Revised:2025-08-06
Contact: *E-mail: zuoyinglin@hec.cn; ZhangYingjun@hec.cn; zhangji@hec.cn
Supported by:
State Key Laboratory of Anti-Infective Drug Development (NO.2015DQ780357) and Enterprise Key Laboratory of Anti-viral Drug Development for Guangdong Province (Grant No.2020B1212070003) and Enterprise Key Laboratory of Anti-viral Drug Development for Guangdong Province (Grant No.2023B1212070004).

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摘要/Abstract

为了提高药物研发的效率,对药物分子进行分子层面的精准设计与控制以实现药物发现的高效性、高选择性、可预测性的“精准化学”势在必行。“精准化学”方法与手段与已有的 “绿色化学”的原子经济性、废物最小化等目标高度契合,但其核心在精准性与效率。在此,本文通过展示“精准化学”在抗癌药物、靶向蛋白降解药物、抗感染药物、心血管/代谢药物、抗炎药物等药物发现的相关示例,进一步对“精准化学”的理念进行深度剖析,从而使“精准化学”更好地服务于药物研发过程。

关键词: 精准化学, 药物发现, 药物合成, 靶向药物, 绿色化学

To enhance the efficiency of drug research and synthesis, the implementation of "Precision Chemistry" characterized by molecular-level precise design and control of drug molecules to achieve highly efficient, selective, and predictable chemical reactions has become imperative. While "Precision Chemistry" aligns with existing goals of "Green Chemistry" such as atom economy and waste minimization, its core emphasis lies in precision and efficiency. These two concepts intersect rather than being subordinate to each other. This review demonstrates the philosophy of "Precision Chemistry" through practical examples of drug discovery and synthesis of anti-cancer drugs, anti-infection drugs, targeted protein degradation drugs、cardiovascular/metabolic drugs, anti-inflammatory drugs, aiming to better understanding the "Precision Chemistry" concept to serve pharmaceutical research and process well.

Key words: Precise Chemistry, Drug Discovery, Drug Synthesis, Targeted drugs, Green chemistry.

引用此文

刘荣, 左应林, 张英俊, 张霁. “精准化学”在药物发现中的应用[J]. 有机化学, doi: 10.6023/cjoc202505031.

Rong Liu, Yinglin Zuo, Yingjun Zhang, Ji Zhang. Emerging Applications of Precise Chemistry in Drug Discovery[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202505031.

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