Inhibitors of Adenosine Deaminase: Continued Studies of Structure‐Activity Relationships in Analogues of Coformycin

Abstract

Synthesis and adenosine deaminase (ADA) inhibitory activity of two analogues of coformycin, containing the imidazo[4,5‐e][1,2,4]triazepine ring system, have been reported as part of the structure‐activity relationship (SAR) studies to explore the factors responsible for the extremely tight‐binding characteristics of coformycins to ADA.

^†In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.

Keywords:

• Adenosine deaminase
• Inhibitors
• Coformycin analogues
• Ring‐expanded (“fat”) purines
• Imidazotriazepines

Acknowledgments

This research was supported by a grant (#9 RO1 AI55452) from the National Institutes of Health. Authors thank Dr. Diana S. Hamilton for advice regarding the reported enzyme kinetics studies.

Notes

^†In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.

^aMolecular modeling studies were performed using Insight/DiscoverTM Software package, available from Molecular Simulations, Inc., San Diego, California.