Erythro-2-Phenyl-9-(2-hydroxy-3-nonyl)adenine and its 8-aza analog were prepared and showed a very high inhibitory activity towards adenosine deaminase (ADA), with K-i 0.55 and 1.67 nM, respectively, and high affinity for A, adenosine receptors, with K-i 28 and 2.8 nM, respectively. To increase affinity for A(1) receptors we introduced a substituent on the N-6 position such as alkyl or cycloalkyl groups, which are present in effective agonists or antagonists. Furthermore, for some compounds, we prepared the two diastereoisomers erythro and threo to verify whether the binding with A(1) receptors is stereoselective, as in ADA. Results show that some of the synthesised compounds are good inhibitors for ADA and good ligands for A(1), and the erythro diastereoisomers are more active than the threo ones. The experimental evidence allows us to hypothesise some similarity in the three dimensional structures of the binding site of the two proteins, ADA and A(1) adenosine receptor, in spite of lacking any homologies in the aminoacid sequences.
ERYTHRO AND THREO 2-HYDROXYNONYL SUBSTITUTED 2-PHENYLADENINES AND 2-PHENYL-8-AZAADENINES: LIGANDS FOR A1 ADENOSINE RECEPTORS AND ADENOSINE DEAMINASE
GIORGI, IRENE;COSTA, BARBARA;MAZZONI, MARIA ROSA;GIUSTI, LAURA
2002-01-01
Abstract
Erythro-2-Phenyl-9-(2-hydroxy-3-nonyl)adenine and its 8-aza analog were prepared and showed a very high inhibitory activity towards adenosine deaminase (ADA), with K-i 0.55 and 1.67 nM, respectively, and high affinity for A, adenosine receptors, with K-i 28 and 2.8 nM, respectively. To increase affinity for A(1) receptors we introduced a substituent on the N-6 position such as alkyl or cycloalkyl groups, which are present in effective agonists or antagonists. Furthermore, for some compounds, we prepared the two diastereoisomers erythro and threo to verify whether the binding with A(1) receptors is stereoselective, as in ADA. Results show that some of the synthesised compounds are good inhibitors for ADA and good ligands for A(1), and the erythro diastereoisomers are more active than the threo ones. The experimental evidence allows us to hypothesise some similarity in the three dimensional structures of the binding site of the two proteins, ADA and A(1) adenosine receptor, in spite of lacking any homologies in the aminoacid sequences.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
