Our research group is involved in the design, synthesis and development of structurally and mechanistically diverse biological and chemotherapeutic agents. The majority of this research effort is expended in one of the most successful areas for the development of potentially active chemotherapeutic agents, antimetabolites. The antimetabolite approach has been used with considerable success in the search for effective antiviral, antibacterial, antiparasitic, and anti-cancer agents.
The design, synthesis and evaluation of the tricyclic nucleoside 5'-phosphate (TCN-P) is an excellent example of the success which can be achieved by using this approach since TCN-P has been recently placed on Phase II clinical trials as an anti-cancer agent. Human cytomegalovirus (HCMV) is a major cause of sickness and death among AIDS victims, infants and organ transplant patients. There is no effective therapy currently for HCMV. However, our research group has designed and synthesized several compounds which are undergoing evaluation for HCMV activity in animal, Phase I and Phase II clinical studies.
Our research group has recently become involved in the design and synthesis of specific compounds as potential anti-AIDS agents. This research is the synthetic component of a rather large NIH Drug Development Program on AIDS research and involves collaborations with biochemists, biochemical pharmacologists, virologists, etc., and complements the anti-cancer and HCMV research.
Total Synthesis of the Naturally Occurring Antibiotic Toyocamycin Using New and Improved Synthetic Procedures," Anthony R. Porcari and Leroy B. Townsend, Nucleosides & Nucleotides, 18, 153-159, (1999).
"Acyclic Pyrrolo[2,3-d]pyrimidine Analogs as Antiviral Agents" Leroy B. Townsend and John C. Drach, United States Patent, No. RE36,2879 granted on 6 April 1999.
"Synthesis and Regioselective Ribosylation of 6,7-Dichloroimidazo[4,5-b]quinolin-2-one," Zhijian Zhu, Blaise Lippa, and Leroy B. Townsend, J. Org. Chem., 64, 4159-4168 (1999).
"Synthesis of b-L-Lyxofuranosyl Benzimidazoles by an Unexpected Intramolecular Displacement Reaction," Jean-Luc Girardet and Leroy B. Townsend, J. Org. Chem., 64, 4169-4172 (1999).
"Nonnucleoside Pyrrolopyrimidines with a Unique Mechanism of Action against Human Cytomegalovirus," Jennie G. Jaqcobson, Thomas E. Renau, M. Reza Nassiri, Dominica G. Sweier, Julie M. Breitenbach, Leroy B. Townsend, and John C. Drach, Antimicrobial Agents and Chemotherapy, 43(8), 1888-1894 (1999).
"An Unprecedented Nitrogen Elimination Reaction: Mechanistic Studies Using 15N-Labeled 4-Amino-7-benzyl-pyrrolo [2,3-d][1,2,3]triazine-5-carbonitrile," Michael T. Migawa and Leroy B. Townsend, Organic Letters, 1(4), 537-539 (1999).
"Studies Designed to Increase the Stability and Antiviral Activity (HCMV) of the Active Benzimidazole Nucleoside, TCRB," Leroy B. Townsend, Kristjan S. Gudmundsson, Susan M. Daluge, Jiong J. Chen, Zhijian Zhu, George W. Koszalka, Leslie Boyd, Stanley D. Chamberlain, George A. Freeman, Karen K. Biron, and John C. Drach, Nucleosides & Nucleotides, 18(4&5), 509-519 (1999).
"An Efficient Synthesis of 2-Nitropyrrole-3,4-dicarboxamide," Michael T. Migawa and Leroy B. Townsend, Synthetic Communications, 29(21), 3757-3772 (1999).
"Design, Synthesis and Antiviral Activity of a-L-Arabinofuranosyl Derivatives of 2-Substituted 5,6-Dichlorobenzimidazoles," Jean-Luc Girardet, John C. Drach, Stanley D. Chamberlain, George W. Koszalka and Leroy B. Townsend, Nucleosides & Nucleotides, 17, 2389-2401 (1998).