Deazapurine Analogues Bearing a 1H‐Pyrazolo[3, 4‐b]pyridin‐3(2H)‐one Core: Synthesis and Biological Activity. Issue 20 (25th May 2018)

• Record Type: Journal Article
• Authors: Supe, Linda; Afzal, Saira; Mahmood, Abid; Ejaz, Syeda Abida; Hein, Martin; Iaroshenko, Viktor O.; Villinger, Alexander; Lecka, Joanna; Sévigny, Jean; Iqbal, Jamshed; Langer, Peter
• Is Part Of: European journal of organic chemistry. Issue 20/21(2018)
• Page Start: 2629
• Page End: 2644
• Publication Date: 2018-05-25
• Subjects: Organofluorine compounds -- 1, 3‐Diketones -- Deazapurine analogues -- Heterocycles -- Cyclization -- Regioselectivity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201800163
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : 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. Abstract : New deazapurine analogues were prepared and their bioactivity studied. Most of the derivatives exhibited selective and potent inhibition on tissue non‐specific and intestinal alkaline phosphatase and nucleotide pyrophosphatase enzymes.