Synthesis 2014; 46(04): 430-444
DOI: 10.1055/s-0033-1338589
short review
© Georg Thieme Verlag Stuttgart · New York

Functionalized Organozinc Reagents in Medicinal Chemistry: Discovery of Novel Drug Candidates

Achyutharao Sidduri*
a   Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA   Fax: +1(973)6434502   Email: sidduri@aunovamedchem.com
b   Aunova Medchem LLC, Newark, NJ 07103, USA
,
Jefferson W. Tilley
a   Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA   Fax: +1(973)6434502   Email: sidduri@aunovamedchem.com
,
Nader Fotouhi
a   Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA   Fax: +1(973)6434502   Email: sidduri@aunovamedchem.com
› Author Affiliations
Further Information

Publication History

Received: 11 December 2013

Accepted after revision: 07 January 2014

Publication Date:
29 January 2014 (online)


Abstract

Discovery, optimization, and early development of drug candidates are very challenging and require a versatile synthetic chemistry toolbox. Organozinc chemistry is a powerful methodology for carbon–carbon bond formation which tolerates several functional groups that are critical for maintaining good physicochemical properties of drug molecules. Here we demonstrate that organozinc chemistry offers facile solutions to otherwise challenging medicinal chemistry problems commonly encountered during lead optimization. In this review, we summarize several examples in which utilization of organozinc-mediated couplings enabled us to rapidly explore a medicinal chemistry hypothesis using readily available intermediates. This chemistry allowed us to make rapid decisions with limited chemistry resources.

1 Introduction

2.1 Alpha4 Integrin Antagonists

2.2 CRTH2 Antagonists

2.3 Glucokinase (GK) Activators

2.4 Leukotriene B4 (LTB4) Receptor Antagonists

2.5 Janus Activated Kinase 3 (JAK3) Inhibitors

2.6 Synthesis of Novel Scaffolds

3 Conclusions

4 Experimental Methods

 
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