Synthesis and pharmacological evaluation of an 8 beta-bis(2-chloroethyl)amino opiate as a nonequilibrium opioid receptor probe.
8 beta-[Bis(2-chloroethyl)amino]-6,7-didehydro-3-hydroxy-17-methyl-4 ,5 alpha-epoxymorphinan (3) was synthesized from codeine, and its configuration at C-8 was determined by NMR. When evaluated in the guinea pig ileum and mouse vas deferens preparations, 3 was found to be a feeble, reversible agonist in both tissues without any irreversible agonist or antagonist activity. The fact that the 8 beta-bis-(2-hydroxyethyl)amino analogue was devoid of opioid activity suggests that steric hindrance to ligand-receptor association by a bulky 8-substituent may be responsible for this inactivity.
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D014649:Vas Deferens / Q000378:metabolism
D009019:Morphinans; D011957:Receptors, Opioid; C042342:8 beta-(bis(2-chloroethyl)amino)-6,7-didehydro-3-hydroxy-17-methyl-4,5 alpha-epoxymorphinan