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.
Secrist
J A
JA
BioCryst Pharmaceuticals, Inc., Birmingham, Alabama 35244.
Niwas
S
S
Rose
J D
JD
Babu
Y S
YS
Bugg
C E
CE
Erion
M D
MD
Guida
W C
WC
Ealick
S E
SE
Montgomery
J A
JA
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