caa a22 4500 47712674X CHVBK 20180405111652.0 cr unu---uuuuu 170330e19971201xx s 000 0 eng 10.1023/A:1012136030849 doi (NATIONALLICENCE)springer-10.1023/A:1012136030849 Studies on Agents with Mixed NO-Dependent Vasodilating and β-Blocking Activities [Elektronische Daten] [Donatella Boschi, Antonella Di Stilo, Clara Cena, Marco Lolli, Roberta Fruttero, Alberto Gasco] Purpose. A series of derivatives having a propranolol-like moiety linked to NO-donor furoxan substructures were synthesized. The main objective of this investigation was to obtain agents with mixed NO-dependent vasodilating and β-blocking activities. Methods. Most of the target compounds were synthesized from the appropriate furoxans bearing XCH2CH2NH2 (X = O, S, SO2) chains at the 4 position of the ring, using A1(C2H5)3 in methylene chloride solution and (±)2,3-epoxypropyl 1-naphtyl ether. Two of the final products (X = CONH) were obtained by coupling the appropriate furoxancarboxylic acids with N-[2-hydroxy-3-(l-naphthoxy)propyl]-ethylenediamine. β1- and β2-blocking activities were examined on isolated guinea pig right atria and on guinea pig trachea respectively. Vasodilating properties were assessed on endothelium denuded strips of rat aorta. Results. Some derivatives behave as well balanced 'hybrids' displaying NO-dependent vasodilating and β-blocking properties in the same concentration range. Some others display either prevalent β-blocking or vasodilating activity. Generally speaking hybrid formation lowers the affinity for β-receptors, in particular for β2-type, to give an increase in β1/β2 selectivity. Conclusions. The furoxan system is a flexible tool in designing analogues of propranolol whose NO-donating and β-blocking properties are modulated over a wide range. Plenum Publishing Corporation, 1997 NO-donors nationallicence β-blockers nationallicence hybrid drugs nationallicence furoxans nationallicence vasodilation nationallicence Boschi Donatella Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut Di Stilo Antonella Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut Cena Clara Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut Lolli Marco Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut Fruttero Roberta Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut Gasco Alberto Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1750-1758 0724-8741 14:12<1750 1997 14 11095 https://doi.org/10.1023/A:1012136030849 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012136030849 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Boschi Donatella Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut NATIONALLICENCE 700 1- Di Stilo Antonella Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut NATIONALLICENCE 700 1- Cena Clara Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut NATIONALLICENCE 700 1- Lolli Marco Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut NATIONALLICENCE 700 1- Fruttero Roberta Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut NATIONALLICENCE 700 1- Gasco Alberto Dipartimento di Scienza e Tecnologia del Farmacp, Via P. Giuria, 9-, 10125, Torino, Italy aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1750-1758 0724-8741 14:12<1750 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer