title: Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors.
abstract: In an effort to improve diazabicycloalkane-based opioid receptor ligands, N-3(6)-arylpropenyl-N-6(3)-propionyl-3,6-diazabicyclo[3.1.1]heptanes (3A,Ba-i) were synthesized and their affinity and selectivity towards mu-, delta- and kappa-receptors were evaluated. The results of the current study revealed a number of compounds (3Bb, 3Bg and 3Bh) having a high affinity for mu (Ki at mu-receptors ranging from 2.7 to 7.9 nM) versus delta (Ki at delta-receptors > 2000 nM) and versus kappa (Ki at kappa-receptors > 5000 nM) receptors. Molecular modelling carried out on the pair 3Aa/3Ba and on the 3Bh was consistent with the hypothesis that the two series of compounds 3A and 3B interact with the mu-receptor in very different ways.
authors.affiliation: Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, via F. Muroni 23/A, 07100 Sassari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Loriga
authors.forename: Ilaria
authors.initials: I
authors.lastname: Manca
authors.forename: Gabriele
authors.initials: G
authors.lastname: Murineddu
authors.forename: Giorgio
authors.initials: G
authors.lastname: Chelucci
authors.forename: Stefania
authors.initials: S
authors.lastname: Villa
authors.forename: Stefania
authors.initials: S
authors.lastname: Gessi
authors.forename: Lucio
authors.initials: L
authors.lastname: Toma
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cignarella
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Pinna
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu