100524-24-1Relevant articles and documents
Novel, highly potent adenosine deaminase inhibitors containing the pyrazolo[3,4-d]pyrimidine ring system. Synthesis, structure-activity relationships, and molecular modeling studies
Da Settimo, Federico,Primofiore, Giampaolo,La Motta, Concettina,Taliani, Sabrina,Simorini, Francesca,Marini, Anna Maria,Mugnaini, Laura,Lavecchia, Antonio,Novellino, Ettore,Tuscano, Daniela,Martini, Claudia
, p. 5162 - 5174 (2005)
This study reports the synthesis of a number of 1- and 2-alkyl derivatives of the 4-aminopyrazolo[3,4-d]pyrimidine (APP) nucleus and their evaluation as inhibitors of ADA from bovine spleen. The 2-substituted aminopyrazolopyrimidines proved to be potent inhibitors, most of them exhibiting Ki values in the nanomolar/subnanomolar range. In this series the inhibitory activity is enhanced with the increase in length of the alkyl chain, reaching a maximum with the n-decyl substituent. Insertion of a 2′-hydroxy group in the ra-decyl chain gave 3k, whose (R)-isomer displayed the highest inhibitory potency of the series (Ki 0.053 nM), showing an activity 2 orders of magnitude higher than that of (+)-EHNA (Ki 1.14 nM), which was taken as the reference standard. Docking simulations of aminopyrazolopyrimidines into the ADA binding site were also performed, to rationalize the structure-activity relationships of this class of inhibitors.