Practical synthetic approaches to several new """"""""purine-like"""""""" C-nucleosides are described. These substances are structurally related to several new purine nucleoside antimetabolites synthesized recently in our laboratory, namely the 9-deazapurine C-nucleosides and their thieno(3,2-d)pyrimidine congeners which have exhibited a wide spectrum of useful biological activity. Rationales are offered which are based on: a) the demonstrated anticancer, antitrypanosomal and antileishmanial activity of several members of the 9-deazapurine C-nucleosides and b) their potential use as biochemical probes. It is suggested that the candidates may possess chemotherapeutic properties similar to, or better than those of the lead compounds. """"""""In house"""""""" biochemical and biological studies for the proper antitumor evaluations of all target C-nucleosides are described. Other collaborative studies would help evaluate their antiprotozoal properties. Relationships between chemical structures and biological activity should be ascertainable from these investigations.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA024634-10
Application #
3166522
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1988-06-01
Project End
1990-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
10
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Montefiore Medical Center (Bronx, NY)
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10467
Bartlett, M S; Marr, J J; Queener, S F et al. (1986) Activity of inosine analogs against Pneumocystis carinii in culture. Antimicrob Agents Chemother 30:181-3
Stoeckler, J D; Ryden, J B; Parks Jr, R E et al. (1986) Inhibitors of purine nucleoside phosphorylase: effects of 9-deazapurine ribonucleosides and synthesis of 5'-deoxy-5'-iodo-9-deazainosine. Cancer Res 46:1774-8