Structural-based design and synthesis of novel 9-deazaguanine derivatives having a phosphate mimic as multi-substrate analogue inhibitors for mammalian PNPs.

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Hikishima S, Hashimoto M, Magnowska L, Bzowska A, Yokomatsu T

Structural-based design and synthesis of novel 9-deazaguanine derivatives having a phosphate mimic as multi-substrate analogue inhibitors for mammalian PNPs.

Bioorg Med Chem. 2010 Mar 15;18(6):2275-84. doi: 10.1016/j.bmc.2010.01.062. Epub 2010 Feb 4.

PubMed ID

20189401 [ View in PubMed

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Abstract

9-(5',5'-Difluoro-5'-phosphonopentyl)-9-deazaguanine (DFPP-DG) was designed as a multi-substrate analogue inhibitor against purine nucleoside phosphorylase (PNP) on the basis of X-ray crystallographic data obtained for a binary complex of 9-(5',5'-difluoro-5'-phosphonopentyl)guanine (DFPP-G) with calf-spleen PNP. DFPP-DG and its analogous compounds were synthesized by the Sonogashira coupling reaction between a 9-deaza-9-iodoguanine derivative and omega-alkynyldifluoromethylene phosphonates as a key reaction. The experimental details focused on the synthetic chemistry along with some insights into the physical and biological properties of newly synthesized DFPP-DG derivatives are disclosed.

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	IC 50 (nM)	20.2	N/A	N/A	Details
9-(5,5-Difluoro-5-Phosphonopentyl)Guanine	Purine nucleoside phosphorylase	Ki (nM)	10.8	N/A	N/A	Details