N-cubylmethyl substituted morphinoids as novel narcotic antagonists.
N-Cubylmethylnormorphine (1) and N-cubylmethylnoroxymorphone (2) have been synthesized and found to be more potent ligands at the mu and kappa opioid receptors than morphine and oxymorphone respectively. In the guinea-pig ileum preparation, compounds 1 and 2 were characterized as opioid mu antagonists (Ke = 68 and 16 nM, respectively). Compound 2 also showed effective kappa-antagonism (Ke = 22 nM). The narcotic antagonism activity of 1 has been confirmed by in vivo assays.
Cheng
C Y
CY
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, R.O.C.
Hsin
L W
LW
Lin
Y P
YP
Tao
P L
PL
Jong
T T
TT
D000701:Analgesics, Opioid / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D018360:Crystallography, X-Ray; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009269:Nalorphine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009270:Naloxone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; C100554:N-cubylmethylnormorphine; C100555:N-cubylmethylnoroxymorphone; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D009269:Nalorphine