Conformational characteristics of opioid kappa-receptor agonist: crystal structure of (5S,7S,8S)-(-)-N-methyl-N-[7-(1-pyrrolidinyl)-1- oxaspiro[4.5]dec-8-yl]benzeneacetamide (U69,593), and conformational comparison with some kappa-agonists.
(5S,7S,8S)-(-)-N-Methyl-N-[7-(1-pyrrolidinyl)-1- oxaspiro[4.5]dec-8-yl]benzeneacetamide (U69,593) is a potent agonist to opioid kappa-receptor. The crystal structure of U69,593 has been analyzed by the X-ray diffraction method. The molecule, as a whole, took an open conformation, and four cyclic rings composing the main skeleton were far apart from each other. The N and O atoms substituted for the cyclohexane ring were all in the equatorial position. The best planes of two 5-membered rings were almost perpendicular to that of the cyclohexane ring, and the N-methylamide linkage was also orthogonal to this ring plane. The conformation of the U69,593 molecule was compared with other kappa-agonists.
Doi
M
M
Osaka University of Pharmaceutical Sciences, Japan.
Ishida
T
T
Inoue
M
M
D044482:Benzeneacetamides; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000032:analysis* / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D014961:X-Ray Diffraction
D044482:Benzeneacetamides; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C045444:U 69593