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Synthesis and Evaluation of a New Series of 3,5‐bis((5‐bromo‐6‐methyl‐2‐ t ‐aminopyrimidin‐4‐yl)thio)‐4 H ‐1,2,4‐triazol‐4‐amines and their Cyclized Products ‘Pyrimidinylthio Pyrimidotriazolothiadiazines’ as 15‐ Lipo‐Oxygenase Inhibitors
Author(s) -
Asghari Tayebe,
Bakavoli Mehdi,
Rahimizadeh Mohammad,
Eshghi Hossein,
Saberi Sattar,
Karimian Azam,
Hadizadeh Farzin,
Ghandadi Moreteza
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12375
Subject(s) - chemistry , thio , nucleophile , piperazine , ring (chemistry) , hydrogen bond , nucleophilic substitution , triazole , stereochemistry , chlorine atom , pyrimidine , amine gas treating , medicinal chemistry , molecule , organic chemistry , catalysis
A series of new 3,5‐bis((5‐bromo‐6‐methyl‐2‐ t ‐aminopyrimidin‐4‐yl)thio)‐4 H ‐1,2,4‐triazol‐4‐amines and their cyclized products ‘pyrimidinylthio pyrimidotriazolothiadiazines’ were designed, synthesized, and evaluated as potential inhibitors of 15‐lipo‐oxygenase (15‐ LO ). Their syntheses started by initial condensation of 2:1 equivalents of pyrimidine with triazole and subsequent nucleophilic displacement of the chlorine atoms with secondary amines and finally cyclocondensation in the presence of Na NH 2 . The compounds 4d and 4f showed the best IC 50 of 15‐ LO inhibition ( IC 50 = 9 and 12 μ m , respectively). Compounds 4a – g were docked into 15‐ LO . We suggest that the hydrogen bonds in quaternary nitrogen of piperazine ring of compounds 4d and 4f appear to play major role in lipo‐oxygenase inhibition by this set of synthesized analogs and hydrophobic nature of this protein's binding site should be considered in ongoing investigations.