Document Report Card

ID: ALA1131096

Journal: J Med Chem

Title: 2-[N-Acylamino(C1-C3)alkyl]indoles as MT1 melatonin receptor partial agonists, antagonists, and putative inverse agonists.

Authors: Spadoni G, Balsamini C, Bedini A, Diamantini G, Di Giacomo B, Tontini A, Tarzia G, Mor M, Plazzi PV, Rivara S, Nonno R, Pannacci M, Lucini V, Fraschini F, Stankov BM.

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]GTPgammaS), 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.

CiteXplore: 9733487

DOI: 10.1021/jm970721h