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

被引：335

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

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