Kenner C. Rice, Ph.D.
Chemical Biology Research Branch, Drug Design and Synthesis Section
5625 Fishers Lane
Bulding 5625FL, Room 4N-03
Rockville, MD 20852
Our major research direction is the elucidation of the structure and function of neurotransmitter systems in the mammalian central nervous system (CNS) in normal, drug-altered, and pathological states and the molecular mechanism of action of CNS active drugs. Organic/medicinal chemistry is the foundation of the multidisciplinary approach utilized in these studies that requires the rational design and chemical synthesis of novel agonists, antagonists, imaging agents, affinity ligands, and other drugs for particular applications. Our principal focus is the application of these techniques to study the mechanism of action of abused drugs and the development of medications for the treatment and prevention of drug abuse. Our present research areas are: (1) opioid receptor subtypes, (2) cocaine and other psychomotor stimulants, (3) cannabinoid (marijuana) receptors, (4) the role of corticotropin releasing hormone receptors in the regulation of the hypothalamic-pituitary-adrenal axis coordinating neuroendocrine, autonomic, immune, and behavioral responses to stress, and (5) development of new ligands for PET and SPECT imaging of drug receptors in the CNS of living animals and conscious humans. The multidisciplinary nature of this program requires extensive collaboration with other groups with diverse pharmacological and biological expertise from within and outside of NIH. These studies also require multistep chemical synthesis of gram and larger quantities of target compounds. Our program has provided potential medications, many new research tools, and much valuable technology for drug abuse research. The latter includes the development of the NIH Opiate Total Synthesis that offers synthetic production of both enantiomers of medical opiates and their antagonists and thus independence from foreign sources of opium.
Sulima A, Jalah R, Antoline JFG, Torres OB, Imler GH, Deschamps JR, Beck Z, Alving CR, Jacobson AE, Rice KC, Matyas GR. A Stable Heroin Analogue That Can Serve as a Vaccine Hapten to Induce Antibodies That Block the Effects of Heroin and Its Metabolites in Rodents and That Cross-React Immunologically with Related Drugs of Abuse. J Med Chem. 2018;61(1):329-343.
Truong PM, Hassan SA, Lee YS, Kopajtic TA, Katz JL, Chadderdon AM, Traynor JR, Deschamps JR, Jacobson AE, Rice KC. Modulation of opioid receptor affinity and efficacy via N-substitution of 9β-hydroxy-5-(3-hydroxyphenyl)morphan: Synthesis and computer simulation study. Bioorg Med Chem. 2017;25(8):2406-2422.
Selfridge BR, Deschamps JR, Jacobson AE, Rice KC. Synthesis of enantiopure 10-nornaltrexones in the search for Toll-like receptor 4 antagonists and opioid ligands. J Org Chem. 2014;79(11):5007-18.
Hiebel AC, Lee YS, Bilsky E, Giuvelis D, Deschamps JR, Parrish DA, Aceto MD, May EL, Harris LS, Coop A, Dersch CM, Partilla JS, Rothman RB, Cheng K, Jacobson AE, Rice KC. Probes for narcotic receptor mediated phenomena. 34. Synthesis and structure-activity relationships of a potent mu-agonist delta-antagonist and an exceedingly potent antinociceptive in the enantiomeric C9-substituted 5-(3-hydroxyphenyl)-N-phenylethylmorphan series. J Med Chem. 2007;50(16):3765-76.
Selfridge BR, Wang X, Zhang Y, Yin H, Grace PM, Watkins LR, Jacobson AE, Rice KC. Structure-Activity Relationships of (+)-Naltrexone-Inspired Toll-like Receptor 4 (TLR4) Antagonists. J Med Chem. 2015;58(12):5038-52.
Related Scientific Focus Areas
This page was last updated on September 12th, 2018