Mark L. Trudell University Research Professor – Organic Chemistry & Pharmacophor Synthesis B.S., Hope College 1983 Ph.D., University of Wisconsin, Milwaukee 1989 email: mtrudell@uno.edu phone: (504) 280-7339 office: CBS 320

Research Interests One of the main areas of research in my group is the synthesis and pre-clinical evaluation of the biological and behavioral effects of novel compounds targeted for the monoamine transporters. These compounds are designed to aide in the elucidation of the mechanism of action of the monoamine transporters as well as provide leads toward the development of therapeutic agents for cocaine addiction and depression. Novel compounds based on the structures of potent dopamine and serotonin uptake inhibitors (e.g. benztropine, cocaine, GBR 12909, meperidine, fluoxetine, paraoxetine) are synthesized and tested in vitro and in vivo to investigate the structure-activity relationships at the dopamine, serotonin and norepinephrine transporters. From these studies several lead compounds have been identified to probe various aspects of dopamine and serotonin transporter composition and function. These studies are fundamental towards understanding the mechanism of action of cocaine and depression as well as for the development of new therapeutic agents. A second major area of research is directed toward the synthesis of the naturally occurring amphibian alkaloids (e.g., decahydroquinolines, epibatidine indolizidines and pyrrolidines). These alkaloids have been shown to elicit their pharmacological activity via interaction with nicotinic acetylcholine receptor-ion channels in both the central and the peripheral nervous systems. Epibatidine has been isolated for the Ecuadorian poison dart frog Epipedobates tricolor and has been shown to possess potent analgesic activity mediated by occupation of acetylcholine nicotinic receptors in the brain, while the decahydroquinline 275B indolizidine 195B and pyrrolidine 225H have been shown to be non-competitive ion channel blockers. The synthesis of these natural products as well as related-analogues is under investigation to study the structure-activity relationships of these novel alkaloids in search of new pharmacological strategies and therapeutic agents for the nicotinic acetylcholine receptor-ion channel mediated disorders and disease states.

Selected Publications "Synthesis of Dopamine Transporter Selective 3-(Diarylmethoxymethyl)-8-alkyla4yl-8- azabicyclo[3.2.1] octane Derivatives." Zhang, S.; Izenwasser, S.; Wade, D.; Trudell, M. L. Bioorg. Med. Chem 2006, 14, 7943-7952. "Oxidative Cyclization of N-Alkyl-o-methyl-arenesulfon -amides to Biologically Important Saccharin Derivatives." Xu, L.; Shu, H.; Liu, Y.; Zhang, S.; Trudell, M. L. Tetrahedron 2006, 62, 7902-7910. "Structure-Activity Studies of 3’,4’-Dichloromeperidine Analogues at Dopamine and Serotonin Transporters." Rhoden, J.; Bouvet, M.; Izenwasser, S.; Wade, D.; Lomenzo, S. A.; Trudell, M. L. Bioorg. Med. Chem. 2005, 13 , 5623-5634. "Selective Oxidation of Benzylic Alcohols and TBDMS Ethers to Carbonyl Compounds with CrO3-H5IO6" Zhang, S.; Xu, L.; Trudell, M. L. Synthesis 2005, (10), 1757-1760. "Synthesis and Biological Evaluation of Meperidine Analogues at Monoamine Transporters," Lomenzo, S. A.; Rhoden, J.; Izenwasser, S.; Wade, D.; Kopajtic, T.; Katz^,J. L.; Trudell, M. L. J. Med. Chem 2005, 1336-143. "Novel N-Dealkylation of N-Alkyl Sulfonamides and N,N-Dialkyl Sulfonamides with Perodic Acid catalyzed by Chromium (III) Acetate Hydroxide." Xu, L.; Zhang, S.; Trudell, M. L. Synlett. 2004, 1901-1904. "Novel Chromium(VI) Catalyzed Oxidation of N-Alkylamides to Imides with Periodic Acid." Xu, L.; Zhang, S.; Trudell, M. L. Chem Commun. 2004, 1668-1669. "Stereoselective Synthesis of the cis 275B Decahydroquinoline ring System." Banner, E. J.; Stevens, E. D.; Trudell. M. L. Tetrahedron Lett 2004, 45, 4411-4414. "Synthesis and Monoamine Transporter Binding of 2-(Diarylmethoxy-methyl)-3 b-aryltropane Derivatives." Xu, L; Kulkarni, S. K.; Izenwasser, S.; Katz, J. L.; Kopajtic, T.;, Lomenzo, S. A.; Newman, A.; Trudell, M. L. J. Med. Chem. 2004, 47, 1676-1682. "A Short and Efficient Synthesis of (±)-Epibatidine." Zhang, C.; Trudell, M. L. J. Org Chem. 1996, 61, 7189-7191.