Synthesis and biological evaluation of 1,1-difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids possessing a N9-purinylmethyl functional group at the ring. a new class of inhibitors for purine nucleoside phosphorylases.
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Yokomatsu T, Hayakawa Y, Suemune K, Kihara T, Soeda S, Shimeno H, Shibuya S
Synthesis and biological evaluation of 1,1-difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids possessing a N9-purinylmethyl functional group at the ring. a new class of inhibitors for purine nucleoside phosphorylases.
Bioorg Med Chem Lett. 1999 Oct 4;9(19):2833-6.
- PubMed ID
- 10522701 [ View in PubMed]
- Abstract
1,1-Difluoro-2-(tetrahydro-3-furanyl)ethylphosphonic acids cis-3 and trans-3 possessing a N9-purinylmethyl functionality at the ring were synthesized and tested as "multi-substrate analogue" inhibitors for purine nucleoside phosphorylases. Radical cyclization of allyic alpha,alpha-difluorophosphonate (E)-7 was applied to construct the alpha,alpha-difluorophosphonate-functionalized tetrahydrofuranyl moiety. The IC50 values of cis-3 and trans-3 for human erythrocyte PNP-catalyzed phosphorylation of inosine were determined to be 88 and 320 nM, respectively. The stereochemistry of the inhibitors was found to affect significantly the inhibitory potency.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 9-(5,5-Difluoro-5-Phosphonopentyl)Guanine Purine nucleoside phosphorylase Ki (nM) 53 N/A N/A Details 9-(5,5-Difluoro-5-Phosphonopentyl)Guanine Purine nucleoside phosphorylase IC 50 (nM) 540 N/A N/A Details 9-(5,5-Difluoro-5-Phosphonopentyl)Guanine Purine nucleoside phosphorylase IC 50 (nM) 380 N/A N/A Details