Structural requirements for antitussive activity in some novel 16‐substituted derivatives of 6, 14‐endoethenotetrahydrothebaine

Structural requirements for antitussive activity in some novel 16-substituted derivatives of 6,14-endoethenotetrahydrothebaine Sm,-Powerful morphine-like analgesics and narcotic antagonists have been found in derivatives of 6,14-endoethenotetrahydrothebaine (Bentley, Boura & others, 1965; Bentley and Hardy, 1967; Blane, Boura & others, 1967). Many of these compounds resemble other narcotics by causing depression of medullary centres mediating the cough reflex, and a search was therefore made within this seric for an antitussive agent in which some dissociation of other morphinelike properties was apparent. The work led to the finding that substitution in the 16-position with an alkyl group resulted in the production of compounds possessing powerful antitussive properties, but having less prominent analgesic and other morphine-like actions than the unsubstituted compound (I ; R=H) which is a highly potent analgesic.