Wonderful Opportunities for Drug Development Based on Prodrugs and Codrugs

Abraham Nudelman, Chemistry - Medicinal Chemistry Diviison, Bar Ilan Unniversity, Ramat Gan, Israel (nudelman@biu.ac.il)

To overcome many of the problems encountered in the course of drug development, such as; poor aqueous solubility, toxicity, lack of specificity, instability, unpleasant taste or odor, etc., two major approaches have been developed, involving the use of prodrugs and codrugs as suitable clinical candidates. Prodrugs are defined as inactive substances, which upon metabolic activation release the active drug. Codrugs are substances wherein two or more active agents are covalently linked, that when metabolized release the synergistically active components of the administered substance. In recent years, prodrugs and codrugs comprise a major group of substances approved for clinical use. Our investigations led to the discovery of biologically active compounds in a variety of fields including: water soluble prodrugs; antischizophrenic codrugs; prodrugs and codrugs of various types of anticancer agents; codrugs of analgesics; codrug inducers of hemoglobin biosynthesis; lipophilic prodrugs of depigmenting agents. These areas of research will be discussed in the presentation.

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Abstract Reference & Short Personal Biography of Presenting Author

Prof. Abraham Nudelman received his Ph.D. under the direction of Nobel Laureate Prof. Donald Cram at UCLA. Established the Division of Medinal Chemistry at the Chemistry Department of Bar Ilan Universitty. Published about 150 papers most of them in Medicinal Chemistry and Drug Development. He has under his name some 80 patents.

In collaboration with Dr. Hugo Gotlieb he published the artcle: NMR Chemical Shifts of Common Laboratory Solvents as Trace Impurities. H. E. Gottlieb, V. Kotlyar and A. Nudelman. J. Org. Chem.1997, 62, 7512-7515”, which as become the “Most Read” paper in the history of the Journal of Organic Chemistry, and has been cited by close to 4000 times.

A large volume of his investugations have dealt with the dvelopment of prodrugs and codrgus, three ofwhich have reached human clinical trials.

Among his discoveruies is a Novel, Patented Process for the Synthesis of Etoposide - The process was licensed to Teva Pharmaceuticals, which synthesized and marketed this compound for many years.