290342-18-6Relevant academic research and scientific papers
Synthesis of (+)- and (-)-cis-2-[(1-adamantylamino)-methyl]-1-phenylcyclopropane derivatives as high affinity probes for σ1 and σ2 binding sites
Marrazzo, Agostino,Prezzavento, Orazio,Pappalardo, Maria S,Bousquet, Ennio,Iadanza, Manuela,Pike, Victor W,Ronsisvalle, Giuseppe
, p. 45 - 53 (2007/10/03)
Selective ligands for either sigma1 (σ1) or σ2 binding sites are potentially useful for gaining a better understanding of the physiological functions of these proteins. Moreover, potent and selective homochiral σ1/su
Synthesis and pharmacological evaluation of potent and enantioselective σ1 and σ2 ligands
Marrazzo, Agostino,Prezzavento, Orazio,Pasquinucci, Lorella,Vittorio, Franco,Ronsisvalle, Giuseppe
, p. 181 - 189 (2007/10/03)
In a previous study we found that substitutions of the (+)-cis-N-normetazocine nucleus of (+)-MPCB with 1-adamantanamine provide the compound (±)-10 with high affinity and selectivity for σ receptors. Starting with this result we have synthesized a new series of eight 1-phenyl-2-cyclopropylmethylamines structurally related to (±)-10, and binding affinities, with respect to σ1, σ2, opioid and dopaminergic D2 receptors, have been reported. All compounds showed a negligible opioid and dopaminergic affinity and high selectivity for σ receptors. Modifications on the amino moiety and methylcarboxyester group of 10 provide compounds with different σ1 and σ2 binding affinity and selectivity. Moreover, we have also synthesized the respective enantiomers of componds (±)-10 and (±)-18 in order to evaluate the enantioselectivity for σ1 and σ2 receptors. The binding data showed that carboxymethylester on the cyclopropane ring was more critical for enantioselectivity than the hydroxymethylenic group. In fact, the (-)-10 enantiomer showed a preference for σ1 whereas (+)-10 showed a preference for σ2.
Substituted 1-phenyl-2-cyclopropylmethylamines with high affinity and selectivity for sigma sites
Ronsisvalle, Giuseppe,Marrazzo, Agostino,Prezzavento, Orazio,Pasquinucci, Lorella,Falcucci, Barbara,Di Toro, Rosanna,Spampinato, Santi
, p. 1503 - 1513 (2007/10/03)
A series of 1-phenyl-2-cyclopropylmethylamines structurally related to (+)- and (-)-MPCB were synthesized and their binding affinities for σ1, σ2, opioid and dopamine (D2) receptors were evaluated. Substitution of the cis-N-normetazocine with different aminic moieties provided compounds with high affinity and selectivity for σ binding sites with respect to opioid and dopamine (D2) receptors. The observed increase in σ2 affinity as compared to the parent (+)-MPCB, supports the idea that the particular stereochemistry of (+)-cis-N-normetazocine affects σ1 selectivity but does not affect σ1 affinity. The (±)-cis isomers of methyl 2-[(1-adamantylamino)methyl]-1-phenylcyclopropane-1-carboxylate (18) displayed a higher affinity and selectivity for the σ1 and σ2 receptor subtypes compared to the (±)-trans 19. Interestingly, the enantiomer (-)-cis 18 displayed a preference for σ1 receptor subtype whereas the (+)-cis 18 did for σ2. These results prompt us to synthesize compounds with modification of nitrogen and carboxyl groups. The compounds obtained showed high affinities and selectivity for σ sites. Moreover, modifications of carboxyl groups provided compounds with the highest affinities in the series. In particular, compound 25 with reverse-type ester showed a K(i) of 0.6 and 4.05nM for σ1 and σ2 binding sites, respectively. Copyright (C) 2000 Elsevier Science Ltd.
