71083-01-7Relevant articles and documents
Hybrids of Imatinib with Quinoline: Synthesis, Antimyeloproliferative Activity Evaluation, and Molecular Docking
Bastos, Monica,Boechat, Nubia,Canzian, Henayle,Cunha, Anna,Dantas, Rafael,Hoelz, Lucas,Junior, Floriano,Marinho, Debora,Oliveira, Andressa,Pimentel, Luiz,Santos, Carine
, (2022/03/27)
Imatinib (IMT) is the first-in-class BCR-ABL commercial tyrosine kinase inhibitor (TKI). However, the resistance and toxicity associated with the use of IMT highlight the importance of the search for new TKIs. In this context, heterocyclic systems, such as quinoline, which is present as a pharmacophore in the structure of the TKI inhibitor bosutinib (BST), have been widely applied. Thus, this work aimed to obtain new hybrids of imatinib containing quinoline moieties and evaluate them against K562 cells. The compounds were synthesized with a high purity degree. Among the produced molecules, the inhibitor 4-methyl-N3-(4-(pyridin-3-yl)pyrimidin-2-yl)-N1-(quinolin-4-yl)benzene-1,3-diamine (2g) showed a suitable reduction in cell viability, with a CC50 value of 0.9 μM (IMT, CC50 = 0.08 μM). Molecular docking results suggest that the interaction between the most active inhibitor 2g and the BCR-ABL1 enzyme occurs at the bosutinib binding site through a competitive inhibition mechanism. Despite being less potent and selective than IMT, 2g is a suitable prototype for use in the search for new drugs against chronic myeloid leukemia (CML), especially in patients with acquired resistance to IMT.
Conjugate Addition Routes to 2-Alkyl-2,3-dihydroquinolin-4(1H)-ones and 2-Alkyl-4-hydroxy-1,2-dihydroquinoline-3-carboxylates
Kingsbury, Alex,Brough, Steve,McCarthy, Antonio Pedrina,Lewis, William,Woodward, Simon
supporting information, p. 1011 - 1017 (2019/12/27)
Under CuBr·SMe2/PPh3 catalysis (5/10 mol-%) RMgCl (R = Me, Et, nPr, CH=CH2, nBu, iBu, nC5H11, cC6H11, Bn, CH2Bn, nC11H23) readily (–78 °C) undergo 1,4-addition to Cbz or Boc protected quinolin-4(1H)-ones to provide 2-alkyl-2,3-dihydroquinolin-4(1H)-ones (14 examples, 54–99 % yield). Asymmetric versions require AlEt3 to Boc-protected ethyl 6-substituted 4(1H)-quinolone-3-carboxylates (6-R group = all halogens, n/i/t-alkyls, CF3) and provide 61–91 % yield, 30–86 % ee; any halogen, Me, or CF3 provide the highest stereoselectivities (76–86 % ee). Additions of AlMe3 or Al(nC8H17)3 provide ≈ 45 and ≈ 75 % ee on addition to the parent (6-R = H). Ligand (S)-(BINOL)P–N(CHPh2)(cC6H11) provides the highest ee values engendering addition to the Si face of the 4(1H)-quinolone-3-carboxylate. Allylation and deprotection of a representative 1,4-addition product example confirm the facial selectivity (X-ray crystallography).
Synthesis and biological evaluation of 4-oxoquinoline-3-carboxamides derivatives as potent anti-fibrosis agents
Zhu, Jun,He, Lin,Ma, Liang,Wei, Zhe,He, Jiqiang,Yang, Zhuang,Pu, Yuzhi,Cao, Dong,Wu, Yuzhe,Xiang, Mingli,Peng, Aihua,Wei, Yuquan,Chen, Lijuan
supporting information, p. 5666 - 5670 (2015/01/08)
Thirty-one 4-oxoquinoline-3-carboxamides derivatives were synthesized and evaluated for their anti-fibrotic activities by the inhibition of TGF-β1-induced total collagen accumulation and anti-inflammatory activities by the inhibition of LPS-stimulated TNF-α production. Among them, three compounds (10a, 10l and 11g) exhibited potent inhibitory effects on both TGF-β1-induced total collagen accumulation and LPS-stimulated TNF-α production. Furthermore, oral administrations of 10l at a dose of 20 mg/kg/day for 4 weeks effectively alleviated lung inflammation and injury, and decreased lung collagen accumulation in bleomycin-induced pulmonary fibrosis model. Histopathological evaluation of lung tissue confirmed 10l as a potential, orally active agent for the treatment of pulmonary fibrosis.
