Synthesis of novel nucleotide analogues possessing a difluoromethylenephosphonato group. Evaluation of the inhibitory activity for purine nucleoside phosphorylase.
Novel nucleotide analogues 1-6 were prepared as "multi-substrate" analogue inhibitors for purine nucleoside phosphorylases (PNPs). The cyclopropane and the tetrahydrofuran moieties of the alkyl spacer connecting a nucleobase and difluoromethylene phosphonic acid were found to be effective for good inhibition of PNPs.
Yokomatsu
T
T
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Hayakawa
Y
Y
Abe
H
H
Shibuya
S
S
Kihara
T
T
Soeda
S
S
Shimeno
H
H
D000192:Actinomycetales / Q000201:enzymology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005663:Furans; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005663:Furans; D007202:Indicators and Reagents; D009943:Organophosphorus Compounds; C018674:tetrahydrofuran; D011683:Purine-Nucleoside Phosphorylase