The synthesis of a number of new analogs of camptothecin are proposed, which incorporate the requisite Alpha-hydroxy lactone moiety in ring E with ring substituents which should confer greater water solubility on the compounds. Thus, referrring to the basic structure of camptothecin, it is planned to synthesize all possible combinations of mono- and dihydroxy or mono- and diamino substituents involving positions 9, 10, 11, 12. Other monofunctional groups in ring A planned are -COOH, CH2OH, CH2NH2. Other structural types are planned. If the basic structures are active in L1210, then syntheses which include water solubilizing substituents will be conducted. The syntheses will be oriented toward obtaining 50-200 mg quantities for initial SAR evaluation in vitro and in vivo.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038996-02
Application #
3177586
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Research Triangle Institute
Department
Type
DUNS #
131606022
City
Research Triangle Park
State
NC
Country
United States
Zip Code
27709