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Deazapurine Analogues Bearing a 1 H ‐Pyrazolo[3,4‐ b ]pyridin‐3(2 H )‐one Core: Synthesis and Biological Activity
Author(s) -
Supe Linda,
Afzal Saira,
Mahmood Abid,
Ejaz Syeda Abida,
Hein Martin,
Iaroshenko Viktor O.,
Villinger Alexander,
Lecka Joanna,
Sévigny Jean,
Iqbal Jamshed,
Langer Peter
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800163
Subject(s) - chemistry , regioselectivity , stereochemistry , alkaline phosphatase , phosphodiesterase , enzyme , nucleotide , docking (animal) , biological activity , biochemistry , catalysis , in vitro , medicine , nursing , gene
A new methodology for the synthesis of fluorinated and non‐fluorinated 1 H ‐pyrazolo[3,4‐ b ]pyridin‐3‐ones was developed. The reactions proceed by cyclization of electron‐rich 3‐amino‐1 H ‐pyrazol‐5(4 H )‐ones with 1,3‐diketones and the products were obtained in good to excellent yields and with excellent regioselectivity. The products, which can be regarded as deazapurine analogues, were tested for the alkaline phosphatase ( h ‐TNAP and h ‐IAP) and nucleotide pyrophosphatase/phosphodiesterase ( h ‐NPP1 and h ‐NPP3) inhibition profile. Most of the derivatives exhibited selective and potent inhibition on tissue non‐specific and intestinal alkaline phosphatase and nucleotide pyrophosphatase (NPP1 and NPP3) enzymes. Possible binding modes of the most potent inhibitors were studied by molecular docking analysis.