1H‐Pyrazole‐Appended Pyridines and Their 1, 2, 4‐Triazine Precursors: A Rational Synthesis and in silico and in vitro Evaluation of Anti‐Cancer Activity. Issue 22 (8th June 2022)

• Record Type: Journal Article
• Authors: Krinochkin, Alexey P.; Shtaitz, Yaroslav K.; Rammohan, Aluru; Butorin, Ilya I.; Savchuk, Maria I.; Khalymbadzha, Igor A.; Kopchuk, Dmitry S.; Slepukhin, Pavel A.; Melekhin, Vsevolod V.; Shcheglova, Anna V.; Zyryanov, Grigory V.; Chupakhin, Oleg N.
• Is Part Of: European journal of organic chemistry. Volume 2022:Issue 22(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-08
• Subjects: Aza-Diels-Alder reaction -- Cancer -- Computational chemistry -- Cycloaddition -- Nucleophilic substitution; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202200227
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: An operationally facile and high yielding one‐pot protocol has been developed for the preparation of pyridines appended with pyrazole via NH linker. This protocol includes SN ipso /aza‐Diels‐Alder reactions in up to 54 % yields starting from 1, 2, 4‐triazine precursors. All the synthesized compounds have been evaluated for their in silico activity against JAK1, SYK, and FAK1 kinases. The most promising compound was tested in vitro using A‐172, Hs578T, and HepG2 cancer cell lines and exhibited considerable cytotoxicity with IC50 values <50 μM in A‐172 and HepG2 cell lines. Anticancer in vitro activity correlates well with the predicted in silico data. Abstract : A straightforward one‐pot pathway for the preparation of pyrazole‐appended pyridines was developed. The most promising compound exhibited considerable cytotoxicity with IC50 values <50 μM in A‐172 and HepG2 cell lines.