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Novel Triazole‐Tethered Derivatives of Nor‐codeine: Synthesis, Radioligand Binding Assay, Docking Study and Evaluation of Their Analgesic Properties
Author(s) -
Gharehnaghadeh Saman,
Salehi Peyman,
Bararjanian Morteza,
Pecio Łukasz,
BabanezhadHarikandei Kosar,
Khoramjouy Mona,
Shahhosseini Soraya,
Faizi Mehrdad
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202003684
Subject(s) - chemistry , docking (animal) , radioligand , analgesic , codeine , azide , stereochemistry , in vivo , opioid , pharmacology , in vitro , receptor , morphine , organic chemistry , biochemistry , medicine , nursing , microbiology and biotechnology , biology
Abstract A series of novel 1,4‐disubstituted 1,2,3‐triazole derivatives of nor‐codeine were synthesized by N ‐demethylation of codeine by a new procedure followed by propargylation of nitrogen and alkyne‐azide cycloaddition reaction. Affinities of all compounds to Mu opioid receptors were evaluated by in vitro radioligand binding assay method. Seven compounds out of all eighteen novel products were selected for in vivo analgesic tail flick test. Most of the synthesized compounds showed promising results in which 3‐((1‐(2‐hydroxy‐3‐phenoxypropyl)‐1 H ‐1,2,3,–triazol‐4‐yl)methyl)‐9‐methoxy‐2,3,4,4a,7,7a hexahydro‐1 H ‐4,12‐methanobenzofuro[3,2‐e]isoquinolin‐7‐ol ( 16 e ) with an ED 50 of 8.68 mg/kg revealed considerable analgesic activity even better than codeine (9.55 mg/kg) as a commercial drug. Also, docking studies were made on Mu opioid receptor (BU72) which showed good agreement with experimental data. The mentioned compound had the highest docking scores of −10.84 and −9.90 kcal/mol for R and S diastereomers, respectively.