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Cinnamoyl Derivatives of 7 α ‐Amino‐ and 7 α ‐(Aminomethyl)‐ N ‐(cyclopropylmethyl)‐6,14‐ endo ‐ethanotetrahydronororipavines are High‐Potency Opioid Antagonists
Author(s) -
Derrick Ian,
Husbands Stephen M.,
Broadbear Jillian,
Traynor John R.,
Woods James H.,
Lewis John W.
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20001220)83:12<3122::aid-hlca3122>3.0.co;2-2
Subject(s) - chemistry , potency , stereochemistry , opioid , receptor , opioid receptor , derivative (finance) , selectivity , methylene , in vivo , antagonist , pharmacology , in vitro , biochemistry , medicinal chemistry , medicine , microbiology and biotechnology , economics , financial economics , biology , catalysis
Methods have been developed for the synthesis of 7 α ‐amino‐ and 7 α ‐(aminomethyl)‐ N ‐cyclopropylmethyl‐6,14‐ endo ‐ethanotetrahydronororipavines and their cinnamoyl derivatives ( Schemes 1 and 3 ). In displacement binding assays, the cinnamoyl derivatives 4c and 5c had high affinity for opioid receptors, but no particular selectivity for any receptor type or differences in affinity between 4c and 5c ( Table 1 ). In tissue assays for opioid receptor function, in which both 4c and 5c were potent antagonists, the aminomethyl derivative 5c was 20‐ to 70‐fold more potent than the amino derivative 4c ( Table 2 ). These data are in keeping with previously reported in vivo data and confirm the major effect of the methylene spacer in 5c .