Synthesis and biological evaluation of 14-alkoxymorphinans. 3. Extensive study on cyprodime-related compounds.
A series of cyprodime-related compounds (2, 4-12, and 26) has been synthesized and evaluated for opioid agonist and antagonist activity with the mouse vas deferens and guinea pig ileum preparations. None of the changes to cyprodime, including the introduction of a 3-OMe group, increasing and decreasing the size of or completely removing the substituent in position 4, replacing the N-cyclopropylmethyl group with an N-allyl group, or replacing the 14-OMe with an 14-OEt substituent, resulted in an improved mu antagonist profile and most were detrimental either in terms of mu selectivity and potency or increased agonist activity. Increasing the length of the substituent in position 4 resulted in a compound (6a) with a very similar profile to that of cyprodime.
Schmidhammer
H
H
Institute of Organic and Pharmaceutical Chemistry, University of Innsbruck, Austria.
Smith
C F
CF
Erlach
D
D
Koch
M
M
Krassnig
R
R
Schwetz
W
W
Wechner
C
C
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis*; D011957:Receptors, Opioid / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects
D009019:Morphinans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; C058450:cyprodime