1999 Fiscal Year Final Research Report Summary
Synthesis and Biological Evaluation of Difluoromethylenephosphonic Acid Derivatives
| Project/Area Number |
10672001
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Chemical pharmacy
|
|---|
| Research Institution | School of Pharmacy,Tokyo University of Pharmacy & Life Science |
|---|
Principal Investigator |
YOKOMATSU Tsutomu Tokyo University of Pharmacy & Life Science, School of Pharmacy, Associate Professor, 薬学部, 助教授 (70158369)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Keywords | Purine nucleoside phosphorylase / Protein-tyrosine phosphatase / Inhibitors / Difluoromethylenephosphonic acids / Structure-activity relation ship |
|---|
| Research Abstract |
1.Synthesis and biological evaluation of novel nucleotide analogues possessing difluoromethylene phosphonic acids. Novel nucleotide analogues derived from connecting purine nucleobases and difluoromethylenephosphonic acid (CFィイD22ィエD2POィイD23ィエD2HィイD22ィエD2) with a variety of alkyl spacer were prepared for "multi-substrate analogue" inhibitors of purine nucleoside phosphorylase (PNPs). The cyclopropane and the tetrahydrofuran moieties of the alkyl spacer connecting a nucleobase and CFィイD22ィエD2POィイD23ィエD2HィイD22ィエD2 were found to be effective for good inhibition of PNPs.
2.Synthesis of α, α-difluorobenzylphosphonic acid derivatives for inhibitors of purotein-tyrosine phosphatase 1B. A series of α, α-difluorobenzylphosphonic acids having a hydrophobic functional group were prepared via the Stille coupling reaction from halogenated α, α-difluorobenzylphosphonates. Evaluation of inhibitory activity toward protein tyrosine phosphatase (PTP 1B) revealed that the ethynyl, phenylthynyl and (E)-styryl groups on the benzene nuclei increased the inhibitory activity upon α, α-defluorobenzylphosphonic acid. Inhibitory activities significantly increased upon introducing both (E)-styryl and bis-methylsulfonamide functional groups onto the benzene nuclei of α, α-difluorobenzylphosphonic acid.
|
