In this paper we describe synthesis and biological assays of some A, ligands more water-soluble than the effective, but very lipophilic. 8-azaadenines and adenines discovered in the past and obtained introducing on N-6 or N(9) substituent a hydroxy group. Five of the new N-6-hydroxyalkyl- and N-6-hydroxycycloalkyl-2-phenyl-9-benzyl-8-azaadenines showed very high affinity (Ki < 40 nM) and selectivity for A, adenosine receptors. Among the 2-phenyl-9-(2-hydroxy-3-alkyl)-8-azaadenines or adenines prepared, the compounds with the higher A, affinity and selectivity resulted 2-phenyl-9-(2-hydroxy-3-propyl)-N-6-cyclopentyl- and cyclohexyl-8-azaadeninewith Ki 2.2 +/- 0.2 nM and 2.8 +/- 0.3 nM respectively. From the point of view of water-solubility, 2-phenyl-9-(2-hydroxy-3-propyl)-8-azaadenine was the most interesting compound, having a CLogP of 1.066991 and a water-solubility of 1.2 mg in L-1. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
NEW N6-OR N(9)-HYDROXYALKYL SUBSTITUTED 8-AZAADENINES OR ADENINES AS AFFECTIVE A1 ADENOSINE RECEPTOR LIGANDS
GIORGI, IRENE;COSTA, BARBARA;LUCACCHINI, ANTONIO
2003-01-01
Abstract
In this paper we describe synthesis and biological assays of some A, ligands more water-soluble than the effective, but very lipophilic. 8-azaadenines and adenines discovered in the past and obtained introducing on N-6 or N(9) substituent a hydroxy group. Five of the new N-6-hydroxyalkyl- and N-6-hydroxycycloalkyl-2-phenyl-9-benzyl-8-azaadenines showed very high affinity (Ki < 40 nM) and selectivity for A, adenosine receptors. Among the 2-phenyl-9-(2-hydroxy-3-alkyl)-8-azaadenines or adenines prepared, the compounds with the higher A, affinity and selectivity resulted 2-phenyl-9-(2-hydroxy-3-propyl)-N-6-cyclopentyl- and cyclohexyl-8-azaadeninewith Ki 2.2 +/- 0.2 nM and 2.8 +/- 0.3 nM respectively. From the point of view of water-solubility, 2-phenyl-9-(2-hydroxy-3-propyl)-8-azaadenine was the most interesting compound, having a CLogP of 1.066991 and a water-solubility of 1.2 mg in L-1. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
