Synthesis and Pharmacological Evaluation of an 8β-Bis(2-chloroethyl)amino Opiate as a Nonequilibrium Opioid Receptor Probe

Article abstract of DOI:10.1021/jm00374a026

8β--6,7-didehydro-3-hydroxy-17-methyl-4,5α-epoxymorphinan (3) was synthesized from codeine, and its configuration at C-8 was determined by NMR.When evaluated in the quinea 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 8β-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.