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.
Copyright 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cattle
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Drug Design*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Erythrocytes / enzymology
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Guanine / analogs & derivatives*
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Guanine / chemical synthesis
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Guanine / chemistry
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Guanine / pharmacology
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Humans
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Hydrogen-Ion Concentration
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Kinetics
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Models, Molecular
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Molecular Structure
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Organophosphonates / chemical synthesis*
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Organophosphonates / chemistry
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Organophosphonates / pharmacology*
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Purine-Nucleoside Phosphorylase / antagonists & inhibitors*
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Purine-Nucleoside Phosphorylase / chemistry
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Purine-Nucleoside Phosphorylase / metabolism
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Spleen / enzymology
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Stereoisomerism
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Structure-Activity Relationship
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Time Factors
Substances
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9-(5',5'-difluoro-5'-phosphonopentyl)-9-deazaguanine
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Enzyme Inhibitors
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Organophosphonates
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Guanine
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Purine-Nucleoside Phosphorylase