Chemical methods will be developed for the preparation of six classes of C-nucleoside derivatives which are close analogs of either synthetic derivatives with established antitumor and/or antiviral activity or natural products. Isosteres and isoelectronic analogs of nicotinamide nucleoside (classes 1 and 2) will by synthesized. These C-nucleosides may show potent antitumor activity by inhibiting IMP-dehydrogenase or they may potentiate the activity of other anticancer drugs whose mode of action involves DNA strand disruption. NAD analogs (class 3) in which the nicotinamide nucleoside is replaced by a class 1 or class 2 C-nucleoside will be prepared. These analogs may be more active that the C-nucleosides of classes 1 and 2. C-Nucleoside analogs (class 4) of the potent antiherpetic and potential antileukemic agents, FMAU and FEAU, will be synthesized by modification of a preformed nucleoside (gamma-uridine) at the sugar moiety. Novel ring transformation reactions will be developed and applied to facile synthesis of antitumor antibiotics, showdomycin and oxazinomycin, and their analogs (classes 5 and 6) from Gamma-uridine. """"""""In house"""""""" biochemical and chemotherapeutic collaborative studies for proper evaluation of the targeted C-nucleosides are described briefly. From these studies, structure-activity relationships should be forthcoming to aid in the development of new agents superior to those currently available for the treatment of cancer and/or viral infection in man.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA033907-04
Application #
3171649
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1983-07-01
Project End
1990-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
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