Structural-based design and synthesis of novel 9-deazaguanine derivatives having a phosphate mimic as multi-substrate analogue inhibitors for mammalian PNPs
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 ω-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.
Get Best Price for1225194-27-39-[7',7'-difluoro-7'-(diethylphosphono)hept-1'-ynyl]-2-N-(N,N-dimethylaminomethylidene)-7-N-(2-nitrophenyl)sulfonyl-1N-(pivaloyloxy)methyl-9-deazaguanine