Alan R. Katritzky, Kazuyuki Suzuki, and Sandeep K. Singh
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200 Abstract
Polymer-supported N-acylation utilizing carbodiimides with additives, direct coupling reagents (phosphonium salts and uronium salts), N-acylazoles, and other reagents have been discussed. Full Text (PDF)
US-driven trends in combinatorial chemistry
Chris Tils
The Institute for Prospective Technological Studies Report Abstract
Combinatorial Chemistry is set to become a core technology for pharmaceutical and chemical companies. In combination with technologies such as High Throughput Screening (HTS), robotics, advanced software and genetics, it has the ability to shorten the time to market for new drugs and make drug discovery a less costly process. Combinatorial chemistry is now also moving into new fields of application like agrochemicals and advanced materials. Full Text (HTML)
Solid-phase parallel synthesis applied to lead development: potent analogues of the GPIIb/IIIa antagonist RWJ-50042
William J. Hoekstra, Bruce E. Maryanoff, Patricia Andrade-Gordon, Judith H. Cohen, Michael J. Costanzo, Bruce P. Damiano, Robert Falotico, Barbara J. Haertlein, Bruce D. Harris, Jack A. Kauffman, Patricia M. Keane, David F. McComsey, John A. Mitchell, Frank J. Villani, Jr. and Stephen C. Yabut
Drug Discovery and Chemical Development Department, The R. W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477, USA Abstract
A series of β-turn peptide mimetics with a nipecotic acid heterocyclic scaffold was designed by NMR analysis of the C-terminal γ-chain of fibrinogen to provide the lead GPIIb/IIIa (fibrinogen receptor) antagonist RWJ-50042. We have employed solid-phase parallel synthesis for the preparation of over 200 analogues of this lead with a protocol of optimization cycles. This strategy produced some nipecotamide analogues with a 100-fold improvement in potency. Full Text (HTML)
Advances in the use of synthetic combinatorial chemistry: Mixture-based libraries
Clemencia Pinilla, Jon R. Appel, Eva Borras & Richard A. Houghten
Torrey Pines Institute for Molecular Studies, San Diego, California, USA
Mixture Sciences, Inc., San Diego, California, USA Abstract
The conceptual and technical approaches that led to the explosive growth of combinatorial chemistry began approximately 20 years ago. In the past decade, combinatorial chemistry has continued to expand with new chemistries, technological improvements and, most importantly, a clear demonstration of its utility in the identification of active compounds for research and drug-discovery programs. This article describes the conceptual and practical breakthroughs that have been critical for the development of synthetic combinatorial methods and includes the most recent developments and applications of mixture-based combinatorial libraries. Full Text (HTML)
A new and efficient multicomponent solid-phase synthesis of 2-acylaminomethylthiazoles
Bernd Henkel, Michael Sax and Alexander Domling
Tetrahedron Letters 44 (2003) 3679–3682 Abstract
A new multicomponent reaction (MCR) for the preparation of 2-substituted thiazole libraries using Rink amide resin is described. Thiazoles are assembled in a one-pot MCR of a thiocarboxylic acid, aldehyde, 3-(N,N-dimethylamino)-2-iso-cyanoacrylate with a resin-bound primary amine. Aliphatic and aromatic thiocarboxylic acids as well as aliphatic and (hetero-) aromatic aldehydes work in the reaction. Cleavage of the product yields the substituted thiazoles in reasonable to good purity. Full Text (PDF)
