N-Ethoxybenzylimidazoles: pH Sensitive linkers for controlled release of cancer therapeutics

ORGN 158

Alice Luong1, Seong Deok Kong1, Gerald Manorek2, Stephen B. Howell2, and Jerry Yang, jerryyang@ucsd.edu1. (1) Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr, MC 0358, La Jolla, CA 92093-0358, (2) Department of Medicine and the Rebecca and John Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, MC 0819, La Jolla, CA 92093
This presentation will highlight a new class of N-linked imidazoles as potential pH-sensitive, cleavable linkers for use in cancer drug delivery systems. These acid-sensitive linkers are designed to exploit the slightly lower extracellular pH of some tumors, endosomes and lysosomes in cells, to trigger the controlled release of therapeutic agents from drug delivery vessels. Cleavage of N-ethoxybenzylimidazoles (NEBIs) exhibit a > 10-fold acceleration in the rate of hydrolysis in mild aqueous acidic solutions (at pH = 5.5) compared to solutions at normal, physiological pH. This presentation will include some initial studies towards the development of NEBIs as linkers for conjugation of cancer therapeutics to drug delivery systems for potential cancer therapy applications.
 

Total Synthesis, Materials, Devices and Switches, Molecular Recognition and Self-Assembly, Biologically-Related Molecules and Processes
8:00 PM-10:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Organic Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007