Automation of Synthesis in Medicinal Chemistry: Progress and Challenges

被引:18
作者
Farrant, Elizabeth [1 ]
机构
[1] New Path Mol Res Ltd, Cambridge CB22 3AT, England
来源
ACS MEDICINAL CHEMISTRY LETTERS | 2020年 / 11卷 / 08期
关键词
Automation; medicinal chemistry; synthesis; autonomy; artificial intelligence; ASSISTED SYNTHESIS; INHIBITORS; DISCOVERY; GENERATION; PLATFORM; DIVERSE; SYSTEM;
D O I
10.1021/acsmedchemlett.0c00292
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Since the 1990s, concerted attempts have been made to improve the efficiency of medicinal chemistry synthesis tasks using automation. Although impacts have been seen in some tasks, such as small array synthesis and reaction optimization, many synthesis tasks in medicinal chemistry are still manual. As it has been shown that synthesis technology has a large effect on the properties of the compounds being tested, this review looks at recent research in automation relevant to synthesis in medicinal chemistry. A common theme has been the integration of tasks, as well as the use of increased computing power to access complex automation platforms remotely and to improve synthesis planning software. However, there has been more limited progress in modular tools for the medicinal chemist with a focus on autonomy rather than automation.
引用
收藏
页码:1506 / 1513
页数:8
相关论文
共 43 条
[1]  
[Anonymous], UK ZAIP FLOW TECHN
[2]  
Baker M., 2016, NATURE, V533, P353, DOI DOI 10.1038/NATURE17990
[3]   Integrated Platform for Expedited Synthesis-Purification-Testing of Small Molecule Libraries [J].
Baranczak, Aleksandra ;
Tu, Noah P. ;
Marjanovic, Jasmina ;
Searle, Philip A. ;
Vasudevan, Anil ;
Djuric, Stevan. W. .
ACS MEDICINAL CHEMISTRY LETTERS, 2017, 8 (04) :461-465
[4]   Reconfigurable system for automated optimization of diverse chemical reactions [J].
Bedard, Anne-Catherine ;
Adamo, Andrea ;
Aroh, Kosi C. ;
Russell, M. Grace ;
Bedermann, Aaron A. ;
Torosian, Jeremy ;
Yue, Brian ;
Jensen, Klavs F. ;
Jamison, Timothy F. .
SCIENCE, 2018, 361 (6408) :1220-+
[5]   Analysis of Past and Present Synthetic Methodologies on Medicinal Chemistry: Where Have All the New Reactions Gone? [J].
Brow, Dean G. ;
Bostrom, Jonas .
JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (10) :4443-4458
[6]  
Campos KR, 2019, SCIENCE NEW YORK NY, V363, P6424
[7]   A Photoredox Coupling Reaction of Benzylboronic Esters and Carbonyl Compounds in Batch and Flow [J].
Chen, Yiding ;
May, Oliver ;
Blakemore, David C. ;
Ley, Steven, V .
ORGANIC LETTERS, 2019, 21 (15) :6140-6144
[8]   Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery [J].
Czechtizky, Werngard ;
Dedio, Jueergen ;
Desai, Bimbisar ;
Dixon, Karen ;
Farrant, Elizabeth ;
Feng, Qixing ;
Morgan, Trevor ;
Parry, David M. ;
Ramjee, Manoj K. ;
Selway, Christopher N. ;
Schmidt, Thorsten ;
Tarver, Gary J. ;
Wright, Adrian G. .
ACS MEDICINAL CHEMISTRY LETTERS, 2013, 4 (08) :768-772
[9]   Rapid Discovery of a Novel Series of Abl Kinase Inhibitors by Application of an Integrated Microfluidic Synthesis and Screening Platform [J].
Desai, Bimbisar ;
Dixon, Karen ;
Farrant, Elizabeth ;
Feng, Qixing ;
Gibson, Karl R. ;
van Hoorn, Willem P. ;
Mills, James ;
Morgan, Trevor ;
Parry, David M. ;
Ramjee, Manoj K. ;
Selway, Christopher N. ;
Tarver, Gary J. ;
Whitlock, Gavin ;
Wrightt, Adrian G. .
JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (07) :3033-3047
[10]   Continuous Flow Photochemistry for the Preparation of Bioactive Molecules [J].
Di Filippo, Mara ;
Bracken, Cormac ;
Baumann, Marcus .
MOLECULES, 2020, 25 (02)