Diversity oriented synthesis: Synthesis, design and qualitative SAR analysis of novel anticancer motifs
Taleb H. Al-Tel College of Pharmacy, University of Sharjah, P.O.Box 27272, Sharjah, UAE
Abstract:
Despite the availability of improved drugs, including targeted cancer therapies, cancer is still one of the leading causes of mortality worldwide. Due to the high failure rate of currently available therapies for most types of cancer, due to lack of selectivity and in most cases chemotherapeutic regimens target all proliferating cells based on the principle that tumor cells proliferate at a faster rate than normal cells, resulting in differential cytotoxicity. Thus, much effort has been made to increase tissue, cell, and target selectivity for chemotherapy. In this regard, extensive synthesis and design of new structural motifs in order to overcome the aforementioned problems and improve antitumor activity and selectivity are highly desirable. The engine of such endeavor, however, will be driven by the development of novel scaffolds that will lead to skeletally diverse molecules to dissect the gap between the chemical and biological space. For this purpose, diversity oriented synthesis to generate a plethora of novel scaffolds, is a powerful and highly productive tool for lead development and analog design. In this meeting, the synthesis, design and qualitative SAR analysis of novel motifs, such as cyclopenta[b]pyranes fused to pyrazolones, tetrahydro-2H-pyrano[3,2-c]pyridazin-3(6H)-one, hexahydropyrano[3,2-c][1,2]diazepin-3(4H)-one and tetrahydropyrano[3,2-b]pyrrol-2(1H)-one (Scheme 1), and assessing their potential as selective anticancer agents, will be presented. 1
Scheme1. Strategies used to understand the SAR of the new scaffolds.
1. Al-Tel, T. H. et. al.; Eur. J. Org. Chem., (2010), DOI: 10.1002/ejoc.201000808; Al-Tel, T. H. et. al. Eur. J. Med. Chem., 2010, 45, 4615-4621; Al-Tel, T. H. et. al. Org. Biomol. Chem., (2010), DOI:10.1039/c0ob00289e.
