Structure-based design of inhibitors of purine nucleoside phosphorylase. 2. 9-Alicyclic and 9-heteroalicyclic derivatives of 9-deazaguanine

J A Secrist 3rd; S Niwas; J D Rose; Y S Babu; C E Bugg; M D Erion; W C Guida; S E Ealick; J A Montgomery

doi:10.1021/jm00065a007

Structure-based design of inhibitors of purine nucleoside phosphorylase. 2. 9-Alicyclic and 9-heteroalicyclic derivatives of 9-deazaguanine

J Med Chem. 1993 Jun 25;36(13):1847-54. doi: 10.1021/jm00065a007.

Authors

J A Secrist 3rd¹, S Niwas, J D Rose, Y S Babu, C E Bugg, M D Erion, W C Guida, S E Ealick, J A Montgomery

Affiliation

¹ BioCryst Pharmaceuticals, Inc., Birmingham, Alabama 35244.

PMID: 8515423
DOI: 10.1021/jm00065a007

Abstract

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.

MeSH terms

Binding Sites
Cycloparaffins / chemical synthesis
Cycloparaffins / pharmacology
Drug Design
Guanine / analogs & derivatives*
Guanine / chemical synthesis
Guanine / metabolism
Guanine / pharmacology
Models, Molecular
Molecular Conformation
Monte Carlo Method
Protein Binding
Purine-Nucleoside Phosphorylase / antagonists & inhibitors*
Purine-Nucleoside Phosphorylase / metabolism
Structure-Activity Relationship
Thermodynamics
X-Ray Diffraction

Substances

Cycloparaffins
Guanine
9-deazaguanine
Purine-Nucleoside Phosphorylase