The Evolution of High-Throughput Experimentation in Pharmaceutical Development and Perspectives on the Future

被引：308

作者：

Mennen, Steven M. ^{[1
,15
]}

Alhambra, Carolina ^{[2
]}

Allen, C. Liana ^{[3
,12
]}

Barberis, Mario ^{[2
]}

Berritt, Simon ^{[4
]}

Brandt, Thomas A. ^{[5
]}

Campbell, Andrew D. ^{[6
]}

Castanon, Jesus ^{[2
]}

Cherney, Alan H. ^{[1
]}

Christensen, Melodie ^{[7
]}

Damon, David B. ^{[5
,12
]}

Eugenio de Diego, J. ^{[2
]}

Garcia-Cerrada, Susana ^{[2
]}

Garcia-Losada, Pablo ^{[2
]}

Haro, Ruben ^{[2
]}

Janey, Jacob ^{[8
]}

Leitch, David C. ^{[13
]}

Li, Ling ^{[3
]}

Liu, Fangfan ^{[9
]}

Lobben, Paul C. ^{[8
,14
]}

MacMillan, David W. C. ^{[10
]}

Magano, Javier ^{[5
]}

McInturff, Emma ^{[5
]}

Monfette, Sebastien ^{[5
]}

Post, Ronald J. ^{[11
]}

Schultz, Danielle ^{[7
]}

Sitter, Barbara J. ^{[5
]}

Stevens, Jason M. ^{[8
]}

Strambeanu, Julia I. ^{[3
]}

Twilton, Jack ^{[10
]}

Wang, Ke ^{[9
]}

Zajac, Matthew A. ^{[3
]}

机构：

[1] Amgen Inc, Drug Subst Technol, 360 Binney St, Cambridge, MA 02142 USA

[2] Ctr Invest Lilly SA, Avda Ind 30, Madrid 28108, Spain

[3] GlaxoSmithKline, API Chem, 1250 South Collegeville Rd, Collegeville, PA 19426 USA

[4] Pfizer Worldwide R&D, Appl Synth Technol, Internal Med, Eastern Point Rd, Groton, CT 06340 USA

[5] Pfizer Worldwide R&D, Chem R&D, Proc Chem, Eastern Point Rd, Groton, CT 06340 USA

[6] AstraZeneca, Pharmaceut Technol & Dev, Silk Rd,Business Pk, Macclesfield SK10 2NA, Cheshire, England

[7] Merck & Co Inc, Proc Res & Dev, Rahway, NJ 07065 USA

[8] Bristol Myers Squibb, Chem & Synthet Dev, 1 Squibb Dr, New Brunswick, NJ 08901 USA

[9] Pfizer Worldwide R&D, Pfizer Global Supply Stat, Pharmaceut Sci, Eastern Point Rd, Groton, CT 06340 USA

[10] Princeton Univ, Merck Ctr Catalysis, Washington Rd, Princeton, NJ 08544 USA

[11] Pfizer Worldwide R&D, Chem R&D, Engn Grp, Eastern Point Rd, Groton, CT 06340 USA

[12] Vertex Pharmaceut, 50 Northern Ave, Boston, MA 02210 USA

[13] Univ Victoria, Dept Chem, STN CSC, POB 1700, Victoria, BC V8W 2Y2, Canada

[14] Thermo Fisher Sci, 29851 Willow Creek Rd, Eugene, OR 97402 USA

[15] Fulcrum Therapeut, Mol Sci, 26 Landsdowne St, Cambridge, MA 02139 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2019年 / 23卷 / 06期

关键词：

automation; catalysis; high-throughput experimentation; screening; SELECTIVE CATALYTIC-HYDROGENATION; SINGLE-ELECTRON TRANSMETALATION; PHOTOREDOX CATALYSIS; DECARBOXYLATIVE ARYLATION; ENABLING TECHNOLOGY; ALPHA-FLUORINATION; MERGING PHOTOREDOX; NICKEL CATALYSIS; SCALE; LIGHT;

D O I：

10.1021/acs.oprd.9b00140

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

High-throughput experimentation (HTE) has revolutionized the pharmaceutical industry, most notably allowing for rapid screening of compound libraries against therapeutic targets. The past decade has also witnessed the extension of HTE principles toward the realm of small-molecule process chemistry. Today, most major pharmaceutical companies have created dedicated HTE groups within their process development teams, invested in automation technology to accelerate screening, or both. The industry's commitment to accelerating process development has led to rapid innovations in the HTE space. This review will deliver an overview of the latest best practices currently taking place within our teams in process chemistry by sharing frequently studied transformations, our perspective for the next several years in the field, and manual and automated tools to enable experimentation. A series of case studies are presented to exemplify state-of-the-art workflows developed within our laboratories.

引用

页码：1213 / 1242

页数：30

共 98 条

[1] Mechanism of the palladium-catalyzed homocoupling of arylboronic acids: Key involvement of a palladium peroxo complex
Adamo, Carlo
Amatore, Christian
Ciofini, Ilaria
Jutand, Anny
Lakmini, Hakim
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (21) : 6829 - 6836
[2] Ahneman DT, 2016, CHEM SCI, V7, P7002, DOI [10.1039/c6sc02815b, 10.1039/C6SC02815B]
[3] A Scalable Route for the Regio- and Enantioselective Preparation of a Tetrazole Prodrug: Application to the Multi-Gram-Scale Synthesis of a PCSK9 Inhibitor
Akin, Anne
Barrila, Mark T.
Brandt, Thomas A.
Dechert-Schmitt, Anne-Marie R.
Dube, Pascal
Ford, David D.
Kamlet, Adam S.
Limberakis, Chris
Pearsall, Andrew
Piotrowski, David W.
Quinn, Brian
Rothstein, Sarah
Salan, Jerry
Wei, Liuqing
Xiao, Jun
[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2017, 21 (12) : 1990 - 2000
[4] Enantioselective organocatalytic α-fluorination of aldehydes
Beeson, TD
MacMillan, DWC
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (24) : 8826 - 8828
[5] Adventures in Atropisomerism: Total Synthesis of a Complex Active Pharmaceutical Ingredient with Two Chirality Axes
Beutner, Gregory
Carrasquillo, Ronald
Geng, Peng
Hsiao, Yi
Huang, Eric C.
Janey, Jacob
Katipally, Kishta
Kolotuchin, Sergei
La Porte, Thomas
Lee, Andrew
Lobben, Paul
Lora-Gonzalez, Federico
Mack, Brendan
Mudryk, Boguslaw
Qiu, Yuping
Qian, Xinhua
Ramirez, Antonio
Razler, Thomas M.
Rosner, Thorsten
Shi, Zhongping
Simmons, Eric
Stevens, Jason
Wang, Jianji
Wei, Carolyn
Wisniewski, Steven R.
Zhu, Ye
[J]. ORGANIC LETTERS, 2018, 20 (13) : 3736 - 3740
[6] An approach to the synthesis of the phomoidrides
Bio, MM
Leighton, JL
[J]. JOURNAL OF ORGANIC CHEMISTRY, 2003, 68 (05) : 1693 - 1700
[7] Selective Catalytic Hydrogenation of Functionalized Nitroarenes: An Update
Blaser, Hans-Ulrich
Steiner, Heinz
Studer, Martin
[J]. CHEMCATCHEM, 2009, 1 (02) : 210 - 221
[8] Selective functionalization of complex heterocycles via an automated strong base screening platform
Boga, Sobhana Babu
Christensen, Melodie
Perrotto, Nicholas
Krska, Shane W.
Dreher, Spencer
Tudge, Matthew T.
Ashley, Eric R.
Poirier, Marc
Reibarkh, Mikhail
Liu, Yong
Streckfuss, Eric
Campeau, Louis-Charles
Ruck, Rebecca T.
Davies, Ian W.
Vachal, Petr
[J]. REACTION CHEMISTRY & ENGINEERING, 2017, 2 (04): : 446 - 450
[9] A scaleable synthesis of methyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate
Boros, Eric E.
Burova, Svetlana A.
Erickson, Greg A.
Johns, Brian A.
Koble, Cecilia S.
Kurose, Noriyuki
Sharp, Matthew J.
Tabet, Elie A.
Thompson, James B.
Toczko, Matthew A.
[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2007, 11 (05) : 899 - 902
[10] Bose P, EP patent, Patent No. [EP1427524 B1, 1427524]

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