title: Computer-aided structure-affinity relationships in a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives binding to the mu-opioid receptor.
abstract: Molecular modeling studies were carried out on a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives with the aim to highlight the main factors modulating their affinity for the mu-opioid receptor. Structure-affinity relationships were developed with the aid of molecular mechanics and semiempirical quantum-mechanics methods. According to our proposed pharmacodynamic model, the binding to the mu-receptor is promoted by the following physico-chemical features: the presence of hydrocarbon fragments on the nitrogen ring frame capable of interacting with one of two hypothesized hydrophobic receptor pockets; a 'correct' orientation of an N-propionyl side chain so as to avoid a sterically hindered region of the receptor; the possibility of accepting a hydrogen bond from a receptor site complementary to the morphine phenol oxygen.
authors.affiliation: Istituto Chimico Farmaceutico e Tossicologico, Università degli Studi di Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Barlocco
authors.forename: G
authors.initials: G
authors.lastname: Cignarella
authors.forename: G
authors.initials: G
authors.lastname: Greco
authors.forename: E
authors.initials: E
authors.lastname: Novellino
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry / Q000378:metabolism*; D011789:Quantum Theory; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D001643:Bridged Bicyclo Compounds; D010879:Piperazines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu