Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)


Pharmaceutical Sciences


College of Graduate Studies

First Advisor

Rosalie K. Crouch

Second Advisor

Jose D. Benmaman

Third Advisor

Charles F. Bean, Jr.

Fourth Advisor

J. Walter Sowell

Fifth Advisor

Kennerly S. Patrick


As a follow up to interest in a new class of agents that have potential for the treatment of arthritic conditions, two series of cocaine derivatives were synthesized. Specifically, an N-alkyl series consisting of the ethyl, n-propyl, isopropyl, n-butyl and benzyl norcocaine derivatives and an N-acyl series consisting of the acetyl, propionyl, butyryl, and benzoyl norcocaine derivatives were synthesized. The structures of these compounds were verified using GC/MS, 1H NMR, and FT-IR with support from elemental analysis. Evaluation of the effect of these cocaine analogs on the inhibition of dopamine uptake represented the biological focus of this project. Each of these series of compounds was evaluated in ligand binding and neurotransmitter uptake blockade assays as part of an ongoing research project at the National Institute of Drug Abuse. This program is designed to screen compounds for their usefulness in the treatment of cocaine abuse. None of the compounds in these two series demonstrated sufficient in vitro activity to warrant animal testing. A separate small series of unique compounds in which the 3-carboxylic acid moiety of benzoylecgonine was reduced to a primary alcohol and esterified with various nonsteroidal antiinflammatory drugs were synthesized. These compounds are potential prodrugs for the esterified NSAID and for benzoylecgonine. They will be evaluated for potential antirheumatic activity as part of a future study.


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