The objective of the proposed research will be to synthesize certain bicyclic diazolo[1,3]oxazine nucleosides from the appropriate monocyclic nucleosides. This study will provide analogs of the naturally occurring nucleosides (inosine, adenosine, guanosine and xanthosine), which will then be tested as substrates and/or inhibitors of the enzymes adenosine deaminase (ADase), adenosine kinase, purine nucleoside phosphorylase (PNPase), and hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). Additional derivatives will be synthesized as deemed necessary in order to establish a structure activity relationship. Physico-chemical studies involving tautomeric forms, pKa's, etc., will be undertaken in efforts to correlate some of these factors with their biological and chemotherapeutic activity. These nucleosides will also be evaluated as anticancer agents both in vitro (in house) and in vivo (NCI). Studies will also be conducted in order to determine if these nucleosides are acting as purine-like compounds, pyrimidine-like compounds or perhaps as a pro-drug of the monocyclic nucleosides which we will be using as our starting materials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA028381-06
Application #
3168125
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1980-08-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1988-06-30
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Pharmacy
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109