title: 2-[N-Acylamino(C1-C3)alkyl]indoles as MT1 melatonin receptor partial agonists, antagonists, and putative inverse agonists.
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.
authors.affiliation: Cattedra di Chemioterapia, Dipartimento di Farmacologia, Università degli Studi di Milano, Via Vanvitelli, 32, I-20129 Milano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Spadoni
authors.forename: C
authors.initials: C
authors.lastname: Balsamini
authors.forename: A
authors.initials: A
authors.lastname: Bedini
authors.forename: G
authors.initials: G
authors.lastname: Diamantini
authors.forename: B
authors.initials: B
authors.lastname: Di Giacomo
authors.forename: A
authors.initials: A
authors.lastname: Tontini
authors.forename: G
authors.initials: G
authors.lastname: Tarzia
authors.forename: M
authors.initials: M
authors.lastname: Mor
authors.forename: P V
authors.initials: PV
authors.lastname: Plazzi
authors.forename: S
authors.initials: S
authors.lastname: Rivara
authors.forename: R
authors.initials: R
authors.lastname: Nonno
authors.forename: M
authors.initials: M
authors.lastname: Pannacci
authors.forename: V
authors.initials: V
authors.lastname: Lucini
authors.forename: F
authors.initials: F
authors.lastname: Fraschini
authors.forename: B M
authors.initials: BM
authors.lastname: Stankov
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008550:Melatonin / Q000378:metabolism*; D051379:Mice; D051381:Rats; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D044094:Receptors, Melatonin; D012965:Sodium Chloride / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D008024:Ligands; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D012965:Sodium Chloride; D019204:GTP-Binding Proteins; D008550:Melatonin