title: Structure of a kappa-opioid receptor misfit: (1S,5R,8R,9R)-2'-hydroxy-5,9-dimethyl-8,2-epoxyethano-6,7-benzomorphan hydrochloride.
abstract: C16H22NO+2.Cl-, Mr = 295.808, monoclinic, P2(1), a = 11.967 (1), b = 12.529 (1), c = 9.9369 (9) A, beta = 93.00 (1) degrees, V = 1487.8 (2) A3, Z = 4, Dm = 1.32 (2), Dx = 1.321 Mg m-3, lambda(Cu K alpha) = 1.54178 A, mu(Cu K alpha) = 2.289 mm-1, F(000) = 632, T = 291 K, final R = 0.040 for 2448 observed reflections. The two molecules present in the asymmetric unit are linked by an extensive network of hydrogen bonds, including several of the less common (C-)H...O and (C-)-H...Cl types. This interpretation is substantiated by a Mulliken population analysis resulting from CNDO/2 calculations. The major effect of the presence of the epoxyethano bridge is a marked flattening about the N atom of the piperidinium ring. Whether this is sufficient to explain the inactivity of the compound at the opioid kappa receptor is not clear.
authors.affiliation: Instituut voor Farmaceutische, Wetenschappen, Katholieke Universiteit Leuven, Belgium.
authors.forename: C L
authors.initials: CL
authors.lastname: Verlinde
authors.forename: N M
authors.initials: NM
authors.lastname: Blaton
authors.forename: C J
authors.initials: CJ
authors.lastname: De Ranter
authors.forename: O M
authors.initials: OM
authors.lastname: Peeters
mesh_terms: D001575:Benzomorphans / Q000138:chemical synthesis; D003460:Crystallization; D003461:Crystallography; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009019:Morphinans / Q000138:chemical synthesis; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D013329:Structure-Activity Relationship
chemical_list: D001575:Benzomorphans; D009019:Morphinans; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C062176:2'-hydroxy-5,9-dimethyl-8,2-epoxyethano-6,7-benzomorphan