%0 Journal Article
%A Settimo, Federico Da
%A Primofiore, Giampaolo
%A Motta, Concettina La
%A Taliani, Sabrina
%A Simorini, Francesca
%A Marini, Anna Maria
%A Mugnaini, Laura
%A Lavecchia, Antonio
%A Novellino, Ettore
%A Tuscano, Daniela
%A Martini, Claudia
%D 2005
%T Novel, Highly Potent Adenosine Deaminase Inhibitors Containing the
Pyrazolo[3,4-d]pyrimidine Ring System. Synthesis, Structure−Activity
Relationships, and Molecular Modeling Studies
%U https://acs.figshare.com/articles/journal_contribution/Novel_Highly_Potent_Adenosine_Deaminase_Inhibitors_Containing_the_Pyrazolo_3_4_i_d_i_pyrimidine_Ring_System_Synthesis_Structure_Activity_Relationships_and_Molecular_Modeling_Studies/3273286
%R 10.1021/jm050136d.s001
%2 https://acs.figshare.com/ndownloader/files/5111005
%K study reports
%K APP
%K series
%K ADA binding site
%K alkyl chain
%K activity 2 orders
%K Docking simulations
%K K i values
%K decyl chain
%K pyrimidine Ring System
%K aminopyrazolopyrimidine
%K Potent Adenosine Deaminase Inhibitors Containing
%K 3 k
%K inhibitor
%K nM
%K EHNA
%K Molecular Modeling Studies
%K decyl substituent
%X 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 n-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.
%I ACS Publications