Premium
Synthesis of Novel Triplets with a 1,3,5‐Trioxazatriquinane Skeleton and Their Pharmacologies for Opioid Receptors
Author(s) -
Nagase Hiroshi,
Kutsumura Noriki
Publication year - 2015
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201500031
Subject(s) - phenethylamine , chemistry , receptor , stereochemistry , agonist , syk , opioid receptor , opioid , chemical synthesis , tricyclic , combinatorial chemistry , in vitro , biochemistry , tyrosine kinase
We designed and synthesized novel triplet molecules with 1,3,5‐trioxazatriquinane skeletons. One class comprises double‐capped triplets with a morphinan skeleton; the other class comprises simple phenol derivatives with phenethylamine moieties. One compound with m ‐phenolic hydroxyl group, called SYK‐146, is a highly selective, potent agonist for the κ receptor, with activity nearly equivalent to that of U‐50488H. The o ‐phenolic isomer of SYK‐146, called SYK‐524, showed potent but non‐selective agonistic activity for the opioid receptors. We also added several simple phenol derivatives to a library of compounds that target opioid receptors, and they showed high hit rates for the receptor. This library might also be expected to show high hit rates for other receptors.