Two novel opioid analogues have been designed by substituting the native d-Ala residues in position 2,2' of biphalin with two residues of d-penicillamine or l-penicillamine and by forming a disulfide bond between the thiol groups. The so-obtained compound 9 containing d-penicillamines showed excellent μ/δ mixed receptor affinities (K i (δ) = 5.2 nM; K i (μ) = 1.9 nM), together with an efficacious capacity to trigger the second messenger and a very good in vivo antinociceptive activity, whereas product 10 was scarcely active. An explanation of the two different pharmacological behaviors of products 9 and 10 was found by studying their conformational properties.
Novel cyclic biphalin analogue with improved antinociceptive properties / Mollica, A., Carotenuto, A., Novellino, E., Limatola, A., Costante, R., Pinnen, F., Stefanucci, A., Pieretti, S., Borsodi, A., Samavati, R., Zador, F., Benyhe, S., Davis, P., Porreca, F., Hruby, V.J.. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 5:9(2014), pp. 1032-1036. [10.1021/ml500241n]
Novel cyclic biphalin analogue with improved antinociceptive properties.
CAROTENUTO, ALFONSO
;NOVELLINO, ETTORE;LIMATOLA, ANTONIO;
2014
Abstract
Two novel opioid analogues have been designed by substituting the native d-Ala residues in position 2,2' of biphalin with two residues of d-penicillamine or l-penicillamine and by forming a disulfide bond between the thiol groups. The so-obtained compound 9 containing d-penicillamines showed excellent μ/δ mixed receptor affinities (K i (δ) = 5.2 nM; K i (μ) = 1.9 nM), together with an efficacious capacity to trigger the second messenger and a very good in vivo antinociceptive activity, whereas product 10 was scarcely active. An explanation of the two different pharmacological behaviors of products 9 and 10 was found by studying their conformational properties.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
