Structure-based design of inhibitors of purine nucleoside phosphorylase. 2. 9-Alicyclic and 9-heteroalicyclic derivatives of 9-deazaguanine.
Alicyclic and heteroalicyclic derivatives of 9-deazaguanine (2-amino-1,5-dihydro-4H-pyrrolo[3,2-d] [pyrimidin-4-one) are, with one exception, potent inhibitors of purine nucleoside phosphorylase (PNP) equaling the corresponding 9-arylmethyl derivatives previously investigated. The mode of binding of these compounds to PNP was determined by X-ray crystallography.
BioCryst Pharmaceuticals, Inc., Birmingham, Alabama 35244.
J A
JA
Secrist
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S
Niwas
J D
JD
Rose
Y S
YS
Babu
C E
CE
Bugg
M D
MD
Erion
W C
WC
Guida
S E
SE
Ealick
J A
JA
Montgomery
D001665:Binding Sites; D003516:Cycloparaffins / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D009010:Monte Carlo Method; D011485:Protein Binding; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014961:X-Ray Diffraction
D003516:Cycloparaffins; D006147:Guanine; C076777:9-deazaguanine; D011683:Purine-Nucleoside Phosphorylase