Early Optimization or Hit-to-Lead Libraries

among the increasing number of reported examples, demonstrate how the focused library approach extends further along the drug-discovery pipeline than the initial HTS screen. 

Martina and F. Quartieri, Use of multicomponent, domino, and other one-pot syntheses on sohd phase powerful tools for the generation of libraries of diverse and complex compounds. Comb. Chem. High Throughput Screening, 2003, 6(7), 693. (ii) N.A. Boyle and K.J. Janda, Formats for combinatorial synthesis solid-phase, hquid-phase and surface, Curr. Opin. Chem. Bio., 2002, 6(3), 339. (iii) T. Carell, E.A. Wintner, A.J. Sutherland, J. Rebek Jr., Y.M. Dunayevskiy and P. Vouros, New promise in combinatorial chemistry synthesis, characterization, and screening of small-molecule libraries in solution, Chem. Bio., 1995, 2(3), 171. 

Synthetic methods, Controlled microwave heating in modem organic synthesis, Angew. Chem. Int. Ed., 2004, 43(46), 6250. (ii) C.J. Cullen, R.C.R. Wootton and A.J. de Mello, Microfluidic systems for high-throughput and combinatorial chemistry, Curr. Opin. Drug Disc. Dev., 2004, 7(6), 798. (iii) S.H. DeWitt, Microreactors for chemical synthesis, Curr. Opin. Chem. Bio., 1999, 3(3), 350. 

Falchetto, G. Bovermann, L. Oberer and H.-J. Roth, Quality control in combinatorial chemistry determinations of amounts and comparison of the purity of LC-MS-purified samples by NMR, LC-UV and CLND, J. Comb. Chem., 2005, 7(3), 364. 

(i) PS. Marshall, B. Leavens, O. Heudi and C. Ramirez-Molina, Liquid chromatography coupled with inductively coupled plasma mass spectrometry in the pharmaceutical industry selected examples, J. Chromatogr. A, 2004, 1056(1-2), 3. (ii) L. Prokai, A. Zharikova, T. Janaky, X. Li, A.C. Braddy, P. Perjesi, L. Matveeva, D.H. Powell and K. Prokai-Tatrai, Integration of mass spectrometry into early-phase discovery and development of central nervous system agents, J. Mass Spec., 2001, 36(11), 1211. 

---