The synthesis of several novel indole melatonin analogues substituted at the 2-position with acylaminomethyl (8−11), acylaminoethyl (5a−k), or acylaminopropyl (13) side chains is reported. On the basis of a novel in vitro functional assay (specific binding of [35S]GTPγS), which can discriminate agonist from partial agonist, antagonist, and inverse agonist ligands, 5a,g,h,j and 13 were shown to be partial agonists, 5d,e and 8−11 competitive antagonists, and 5b,c,k putative inverse agonists. Binding and functional assays were performed on cloned human MT1 receptor. Structure−activity relationship considerations indicate that N-[1-aryl-2-(4-methoxy-1H-indol-2-yl)(C1−C2)alkyl]alkanamides represent a lead structure for this type of ligands.

2-[N-Acylamino(C1-C3)alkyl]indoles as MT1 Melatonin Receptor Partial Agonists, Antagonists, and Putative Inverse Agonists / Spadoni, G.; Balsamini, C.; Bedini, A.; Diamantini, G.; DI GIACOMO, B.; Tontini, A.; Tarzia, G.; Mor, Marco; Plazzi, P. V.; Rivara, Silvia; Nonno, R.; Pannacci, M.; Lucini, V.; Fraschini, F.; Stankov, B. M.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 41:(1998), pp. 3624-3634. [10.1021/jm970721h]

2-[N-Acylamino(C1-C3)alkyl]indoles as MT1 Melatonin Receptor Partial Agonists, Antagonists, and Putative Inverse Agonists.

MOR, Marco;RIVARA, Silvia;
1998

Abstract

The synthesis of several novel indole melatonin analogues substituted at the 2-position with acylaminomethyl (8−11), acylaminoethyl (5a−k), or acylaminopropyl (13) side chains is reported. On the basis of a novel in vitro functional assay (specific binding of [35S]GTPγS), which can discriminate agonist from partial agonist, antagonist, and inverse agonist ligands, 5a,g,h,j and 13 were shown to be partial agonists, 5d,e and 8−11 competitive antagonists, and 5b,c,k putative inverse agonists. Binding and functional assays were performed on cloned human MT1 receptor. Structure−activity relationship considerations indicate that N-[1-aryl-2-(4-methoxy-1H-indol-2-yl)(C1−C2)alkyl]alkanamides represent a lead structure for this type of ligands.
2-[N-Acylamino(C1-C3)alkyl]indoles as MT1 Melatonin Receptor Partial Agonists, Antagonists, and Putative Inverse Agonists / Spadoni, G.; Balsamini, C.; Bedini, A.; Diamantini, G.; DI GIACOMO, B.; Tontini, A.; Tarzia, G.; Mor, Marco; Plazzi, P. V.; Rivara, Silvia; Nonno, R.; Pannacci, M.; Lucini, V.; Fraschini, F.; Stankov, B. M.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 41:(1998), pp. 3624-3634. [10.1021/jm970721h]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1836513
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