Facile synthesis of 8-benzoylthio-2,6-methano-3-benzazocines and 3-benzoylthiomorphinans having small-ring substituents.
Synthesis of 3-cyclopropylmethyl-, 3-cyclobutylmethyl-, and 3-methyl-8-benzoylthio-2,6-methano-3-benzazocines (1j-l) was performed by regio-selective chlorosulfonation of non-narcotic 8-deoxy derivatives (1a-c) followed by reduction and benzoylation. 3-Benzoylthiomorphinans (2h-j) were also obtained by the same method. Compounds having small-ring substituents (1k, 1l, 2i, 2j) were found to be weak but pure mu- and delta-opioid antagonists. The analgetic activity of 1k was almost equal to that of pentazocine.
Hori
M
M
Iwamura
T
T
Morita
T
T
Imai
E
E
Oji
H
H
Kataoka
T
T
Shimizu
H
H
Ban
M
M
Nozaki
M
M
Niwa
M
M
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D001575:Benzomorphans / Q000138:chemical synthesis* / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D008297:Male; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology; D010423:Pentazocine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism
D000700:Analgesics; D001575:Benzomorphans; D009019:Morphinans; D011957:Receptors, Opioid; D010423:Pentazocine