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Wayne W. Harding, Ph.D.

Assistant Professor - Medicinal Chemistry

 Wayne2

Contact Information:

office 1321ccN (tel 212-772-5359), lab 1400N, dept fax 212-772-5332, email wayne.harding@hunter.cuny.edu

Research Summary:

Synthesis and Evaluation of Central Nervous System (CNS) Receptor Ligands  (Typified by the following): Compounds that are 5-HT2A or alpha1 adrenergic receptor antagonists have been shown to block or reverse effects of the psychostimulant drug MDMA (commonly called "Ecstasy") in animal models.  However, the potential value of dual potent 5-HT2A/alpha1 adrenergic receptor antagonists as anti-MDMA therapeutic agents has not been robustly investigated.  Our group is involved in the synthesis and biological evaluations of compounds which modulate serotonergic and adrenergic receptors.  Through our research, we hope to uncover novel dual potent 5-HT2A/alpha1 antagonists which may be useful as chemical tools to study the effects of antagonist potency and selectivity at these and other CNS receptors in the antagonism of MDMA's effects. 

Psychoactive Natural Products: We are investigating plants or plant products that are reputed to possess psychoactive (eg. sedative, anxiolytic, stimulant) properties.  Through traditional natural products isolation and spectroscopic identification techniques as well as in vitro and in vivo biological evaluations, our goal is to chemically and pharmacologically characterize novel psychoactive natural products.  Such molecules and their semi-synthetic derivatives will be useful as receptor-selective pharmacological probes or as potential lead compounds for future drug development.

Selected Publications

Microwave-assisted direct biaryl coupling: first application to the synthesis of aporphines. S. Chaudhary, O. LeGendre, S. Pecic and W.W. Harding Tetrahedron Letters 2009, 50, 2437-2439.

(±)-Nantenine analogs as antagonists at human 5-HT2A receptors: C1 and flexible congeners. S. Chaudhary, O. LeGendre, S. Pecic and W.W. Harding. Biorganic and Medicinal Chemistry Leters 2009, 19, 2530-2532

 Synthetic studies of neoclerodane diterpenes from Salvia divinorum: selective modification of the furan ring. W.W. Harding, M. Schmidt, K. Tidgewell, P. Kannan, K. G. Holden, C. M. Dersch, R. B. Rothman, T. E. Prisinzano. Bioorganic and Medicinal Chemistry Letters 2006, 16, 3170-3174.

Enantioselective synthesis of (2R,3R) and (2S,3S)-2-[(3-chloro-phenyl)-(2-methoxy-phenoxy)-methyl]-morpholine. W.W. Harding, M. Hodge, D. Parrish, J. R. Deschamps, W. Woolverton and T. E. Prisinzano Tetrahedron:Asymmetry 2005, 16, 2249-2256.

Neoclerodane Diterpenes as a novel Scaffold for µ opioid receptor ligands. W.W. Harding, K. Tidgewell, N. Byrd, H. Cobb, C. M. Dersch, E. R. Butelman, R. B. Rothman and T. E. Prisinzano. J. Med. Chem. 2005. 48, 4765-4771.

Salvinicins A and B, new neoclerodane diterpenes from Salvia divinorum. W.W. Harding, K. Tidgewell, M. Schmidt, K. Shah, D. Parrish, J. R. Deschamps, J. Snyder, C. Dersch, R. B. Rothman and T. E. Prisinzano. Organic Letters, 2005, 7, 3017-3020.

Pharmacokinetics of the plant-derived hallucinogen salvinorin A in non-human primates. T.E. Prisinzano, E. R. Butelman, M. S.. Schmidt, W. W. Harding, K. Tidgewell, M. J. Kreek, D. J. Murry Synapse 2005, 58, 208-210.

Determination of Salvinorin A in body fluids by high performance liquid-chromatography-atmospheric pressure chemical ionization. M. S. Schimdt, T. E. Prisinzano, K. Tidgewell, W. Harding, E. R. Butelman, M. J. Kreek and D. J. Murry. Journal of Chromatography B 2005, 818, 221-225.

A facile method for the preparation of deuterium labeled salvinorin A: synthesis of [2,2,2-2H3]-salvinorin A. K. Tidgwell, W. W. Harding, M. Schmidt, K. G. Holden, D.J. Murry and T. E. Prisinzano. Bioorganic and Medicinal Chemistry Letters 2004, 5099-5102.