Dept. of Chemistry

John W. Huffman

Dr. John W. Huffman Research Professor
Organic Chemistry


E-mail: huffman@clemson.edu

Research Interests | Publications

Dr. Huffman earned his B.S. (1954) from Northwestern University followed by his A.M. and Ph.D. (1957) with the late Prof. R. B. Woodward at Harvard. He began his academic career at Georgia Institute of Technology (1957-60) and joined Clemson as assistant professor in 1960. He was an NSF Predoctoral Fellow at Harvard and received an NIH Career Development Award (1965-70). He was a visiting professor at Colorado State University (1982).

Research Interests

The principal emphasis in Dr. Huffman's research group is on the synthesis of analogues and metabolites of delta-9-tetrahydrocannabinol THC), the principal active component of marijuana. The long term goals of this research are two-fold and include the potential development of new pharmaceutical products and an exploration of the geometry of both the cannabinoid brain (CB1) and peripheral (CB2) receptors. Cannabinoid receptors are found in mammalian brain and spleen tissue, however, the structural details of the active sites are currently unknown. Marijuana metabolites are used in drug testing and THC analogues show promise for the treatment of nausea, glaucoma and as appetitie stimulants.

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Publications

Atwood, B. K.; Huffman, J.; Straiker, A.; Mackie, K., JWH018, a common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB1 receptor agonist. British Journal of Pharmacology 2010, 160 (3), 585-593.

Chen, J. H.; Smith, V. J.; Huffman, J. W., 8-Chloro- and 5,8-Dichloro-1-naphthoic Acids. Organic Preparations and Procedures International 2010, 42 (5), 490-493.

Huffman, J. W.; Hepburn, S. A.; Lyutenko, N.; Thompson, A. L. S.; Wiley, J. L.; Selley, D. E.; Martin, B. R., 1-Bromo-3-(1 ',1 '-dimethylalkyl)-1-deoxy-Delta(8)-tetrahydrocannabinols: New selective ligands for the cannabinoid CB2 receptor. Bioorganic & Medicinal Chemistry 2010, 18 (22), 7809-7815.

Huffman, J. W.; Hepburn, S. A.; Reggio, P. H.; Hurst, D. P.; Wiley, J. L.; Martin, B. R., Synthesis and pharmacology of 1-methoxy analogs of CP-47,497. Bioorganic & Medicinal Chemistry 2010, 18 (15), 5475-5482.

Vann, R. E.; Warner, J. A.; Bushell, K.; Huffman, J. W.; Martin, B. R.; Wiley, J. L., Discriminative stimulus properties of Delta(9)-tetrahydrocannabinol (THC) in C57Bl/6J mice. European Journal of Pharmacology 2009, 615 (1-3), 102-107.

Breivogel, C. S.; Lambert, J. M.; Gerfin, S.; Huffman, J. W.; Razdan, R. K., Sensitivity to Delta 9-tetrahydrocannabinol is selectively enhanced in beta-arrestin2-/- mice. Behavioural Pharmacology 2008, 19 (4), 298-307.

Huffman, J. W.; Smith, V. J.; Padgett, L. W., Acylation of N-p-toluenesulfonylpyrrole under Friedel-Crafts conditions: evidence for organoaluminum intermediates. Tetrahedron 2008, 64 (9), 2104-2112.

Huffman, J. W.; Thompson, A. L. S.; Wiley, J. L.; Martin, B. R., Synthesis and pharmacology of 1-deoxy analogs of CP-47,497 and CP-55,940. Bioorganic & Medicinal Chemistry 2008, 16 (1), 322-335.

Marriott, K. S. C.; Huffman, J. W., Recent advances in the development of selective ligands for the cannabinoid CB2 receptor. Current Topics in Medicinal Chemistry 2008, 8 (3), 187-204

Poso, A.; Huffman, J. W., Targeting the cannabinoid CB2 receptor: modelling and structural determinants of CB2 selective ligands. British Journal of Pharmacology 2008, 153 (2), 335-346.

Rajesh, M.; Mukhopadhyay, P.; Hasko, G.; Huffman, J. W.; Mackie, K.; Pacher, P., CB2 cannabinoid receptor agonists attenuate TNF-alpha-induced human vascular smooth muscle cell proliferation and migration. British Journal of Pharmacology 2008, 153 (2), 347-357.

1.Huffman, J. W.; Bushell,, S. M.; Joshi, S. N.; Wiley, J. L.; Martin. B. R. Enantioselective Synthesis of 1-methoxy- and 1-deoxy-2¢-methyl-∆8-tetrahydrocannabinols. New selective ligands for the CB2 receptor. Bioorg. Med. Chem. 2006, 14, 247-262.

2.Marriott, K. C.; Huffman, J. W.; Wiley, J. L.; Martin, B. R. Synthesis and pharmacology of 11-nor-1-methoxy-9-hydroxyhexahydrocannabinols and 11-nor-1-deoxy-9-hydroxyhexahydrocannabinols: new selective ligands for the cannabinoid CB2 receptor. Bioorg. Med. Chem.. 2006, 14, 2386-2397.

3.Huffman, J. W.; Padgett, L. W.; Isherwood, M. L.; Wiley, J. L.; Martin, B. R. 1-Alkyl-2-aryl-4-(1-naphthoyl)pyrroles; new high affinity ligands for the cannabinoid CB1 and CB2 receptors. Bioorg. Med. Chem. Lett. 2006, 16, 5432-5435..

4. Huffman, J. W.; Szklennik, P. V.; Almond, A.; Bushell, K.; Selley, D. E.; He, H.; Cassidy, M. P.; Wiley, J. L.; Martin, B. R. 1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles. Bioorg. Med. Chem. Lett. 2005, 15, 4110-4113.

5. Huffman, J. W.; Padgett, L. W. Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr. Med. Chem. 2005, 12, 1395-1411.

6. Thompson, A. L. S.; Kabalka, G. W.; Akula, M. R.; Huffman, J. W. The conversion of phenols to the corresponding aryl halides under mild conditions. Synthesis, 2005, 547-550.

7. Huffman, J. W.; Zengin, G.;Wu, M.-J.; Lu, J.; Hynd, G.; Bushell, K.; Thompson, A. L. S.; Bushell, S.; Tartal, C.; Hurst, D. P.; Reggio, P. H.; Selley, D. E.; Cassidy, M. P.; Wiley, J. L.; Martin, B. R. Structure–activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB1 and CB2 receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB2 receptor agonists. Bioorg. Med. Chem. 2005, 13, 89-112.

8. Knight, L. W.; Huffman, J. W.; Isherwood, M. L. 2-Bromo-N-(p-toluenesulfonyl)pyrrole: A Robust Derivative of 2-Bromopyrrole, Synlett 2003, 1993-1996.

9. Blázquez, C; Casanova, M. L.; Planas, A.; Gómez del Pulgar, T.; Villanueva, C.; Fernández-Aceñero, M. J.; Aragonés, J.; Huffman, J. W.; Jorcano, J. L.; Guzmán, M. Inhibition of tumor angiogenesis by cannabinoids. FASEB J. 2003, 17, 529-531.

10. Casanova, M. L.; Blazquez, C.; Martinez-Palacio, J.; Villanueva, C.; Fernandez-Acenero, M. J.; Huffman, J. W.; Jorcano, J. L.; Guzman, M. Inhibition of skin tumor growth and angiogenisis in vivo by activation of cannabinoid receptors. J. Clin. Invest. 2003, 111, 43-50.

11. Huffman, J. W.; Miller, J. R. A.; Liddle, J.; Yu, S.; Thomas, B. F.; Wiley, J. L.; Martin, B. R. Structure-activity relationships for 1',1'-dimethylalkyl-?8-tetrahydrocannabinols. Bioorg. Med. Chem. 2003, 11. 1397-1410

12. Huffman, J. W.; Mabon, R.; Wu, M.-J.; Lu, J.; Hart, R.; Hurst, D. P.; Reggio, P. H.; Wiley, J. L.; Martin, B. R. 3-Indolyl-1-naphthylmethanes: new cannabimimetic indoles provide evidence for aromatic stacking interactions with the CB1 cannabinoid receptor, Bioorg. Med. Chem. 2003, 11, 539-549.

13. Huffman, J. W.; Bushell, S. M.; Miller, J. R. A.; Wiley, J. L.; Martin, B. R. 1-Methoxy-, 1-Deoxy-11-hydroxy- and 11-hydroxy-1-methoxy-?8-tetrahydrocannabinols: new selective ligands for the CB2 receptor. Bioorg. Med. Chem. 2002, 10, 4119-4129.

14. Sanchez, C., M.L. de Ceballos, T.G. del Pulgar, D. Rueda, C. Corbacho, G. Velasco, I. Galve-Roperh, J.W. Huffman, S.R.Y. Cajal, and M. Guzman, Inhibition of glioma growth in vivo by selective activation of the CB2 cannabinoid receptor. Cancer Research, 2001. 61(15): p. 5784-5789.

15. Liddle, J. and J.W. Huffman, Enantioselective synthesis of 11-hydroxy-(1 ' S,2 ' R)- dimethylheptyl-Delta(8)-THC, a very potent CB1 agonist. Tetrahedron, 2001. 57(36): p. 7607-7612.

16. Huffman, J.W., J.Z. Lu, G. Hynd, J.L. Wiley, and B.R. Martin, A pyridone analogue of traditional cannabinoids. A new class of selective ligands for the CB2 receptor. Bioorganic & Medicinal Chemistry, 2001. 9(11): p. 2863-2870.

17. Huffman, J.W., J.Z. Lu, D. Dai, A. Kitaygorodskiy, J.L. Wiley, and B.R. Martin, Synthesis and pharmacology of a hybrid cannabinoid. Bioorganic & Medicinal Chemistry, 2000. 8(2): p. 439-447.

18. Huffman, J.W., The search for selective ligands for the CB2 receptor. Current Pharmaceutical Design, 2000. 6(13): p. 1323-1337.

19. Baker, D., G. Pryce, J.L. Croxford, P. Brown, R.G. Pertwee, J.W. Huffman, and L. Layward, Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature, 2000. 404(6773): p. 84-87.

20. Aung, M.M., G. Griffin, J.W. Huffman, M.J. Wu, C. Keel, B. Yang, V.M. Showalter, M.E. Abood, and B.R. Martin, Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2 receptor binding. Drug and Alcohol Dependence, 2000. 60(2): p. 133-140.

21. Martin, B.R., R. Jefferson, R. Winckler, J.L. Wiley, J.W. Huffman, P.J. Crocker, B. Saha, and R.K. Razdan, Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists. Journal of Pharmacology and Experimental Therapeutics, 1999. 290(3): p. 1065-1079.

22. Huffman, J.W., J. Liddle, S. Yu, M.M. Aung, M.E. Abood, J.L. Wiley, and B.R. Martin, 3-(1 ',1 '-dimethylbutyl)-1-deoxy-Delta(8)-THC and related compounds: Synthesis of selective ligands for the CB2 receptor. Bioorganic & Medicinal Chemistry, 1999. 7(12): p. 2905-2914.

23. Chin, C.N., J.W. Murphy, J.W. Huffman, and D.A. Kendall, The third transmembrane helix of the cannabinoid receptor plays a role in the selectivity of aminoalkylindoles for CB2, peripheral cannabinoid receptor. Journal of Pharmacology and Experimental Therapeutics, 1999. 291(2): p. 837-844.

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