85418-82-2Relevant articles and documents
Sulfonamide-based 4-anilinoquinoline derivatives as novel dual Aurora kinase (AURKA/B) inhibitors: Synthesis, biological evaluation and in silico insights
Abdelgawad, Mohamed A.,Al-Sanea, Mohammad M.,Alharbi, Khalid S.,Ali Farahat, Ibrahim,Alzarea, Abdulaziz I.,Alzarea, Sami I.,Bakr, Rania B,El Kerdawy, Ahmed M.,Eldehna, Wagdy M.,Elkamhawy, Ahmed,Elshemy, Heba A. H.,Joo Roh, Eun,Lee, Kyeong,Paik, Sora,Syed Nasir Abbas, Bukhari
, (2020/05/08)
Aurora kinases (AURKs) were identified as promising druggable targets for targeted cancer therapy. Aiming at the development of novel chemotype of dual AURKA/B inhibitors, herein we report the design and synthesis of three series of 4-anilinoquinoline derivatives bearing a sulfonamide moiety (5a-d, 9a-d and 11a-d). The percent inhibition of AURKA/B was determined for all target quinolines, then compounds showed more than 50percent inhibition on either of the enzymes, were evaluated further for their IC50 on the corresponding enzyme. In particular, compound 9d displayed potent AURKA/B inhibitory activities with IC50 of 0.93 and 0.09 μM, respectively. Also, 9d emerged as the most efficient anti-proliferative analogue in the US-NCI anticancer assay toward the NCI 60 cell lines panel, with broad spectrum activity against different cell lines from diverse cancer subpanels. Docking studies, confirmed that, the sulfonamide SO2 oxygen was involved in a hydrogen bond with Lys162 and Lys122 in AURKA and AURKB, respectively, whereas, the sulfonamide NH could catch hydrogen bond interaction with the surrounding amino acid residues Lys141, Glu260, and Asn261 in AURKA and Lys101, Glu177, and Asp234 in AURKB. Furthermore, N1 nitrogen of the quinoline scaffold formed an essential hydrogen bond with the hinge region key amino acids Ala213 and Ala173 in AURKA and AURKB, respectively.
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).
Antiviral activity of 4-oxoquinoline-3-carboxamide derivatives against bovine herpesvirus type 5
Pinto, Ana Maria V.,Leite, José Paulo G.,Marinho, Robson S.S.,Forezi, Luana da S.M.,Batalha, Pedro N.,Boechat, Fernanda da C.S.,Cunha, Anna C.,Silva, David O.,Gama, Ivson L.,Faro, Letícia V.,de Souza, Maria C.B.V.,Paix?o, Izabel Christina P.
, p. 13 - 20 (2020/10/21)
Background: Bovine herpesvirus type 5 is an important agent of meningoencephalitis in cattle and has been identified in outbreaks of bovine neurological disease in several Brazilian states. In recent years, oxoquinoline derivatives have become an important focus in antiviral drug research. Methods: The cytotoxicity and anti BoHV-5RJ42/01 activity of a set of synthetic 4-oxoquinoline derivatives 4a-k were assayed on Madin-Darby Bovine Kidney cell and antiviral activity by plaque reduction assay. Results: The most promising substance (4h) exhibited CC50 and EC50 values of 1,239 μM ±5.5 and 6.0 μM ±1.5, respectively, with an SI =206. Two other compounds 4j (CC50 = 35 μM ±2 and EC50 = 24 μM ±7.0) and 4k (CC50= 55 μM ±2 and EC50 = 24 μM ±5.1) presented similar inhibitory profile and selectivity indexes of 1.4 and 2.9, respectively. The results of the time-of-addition studies revealed expressive reduction of virus production (≥80%) in different stages of virus replication cycle except for compound 4h that slightly inhibited virus yield in the first 2 h post infection, but it showed expressive virus inhibition after this time. Conclusions: All three compounds slightly interact with the virus on the virucidal assay and they are not able to block virus attachment and penetration. Antiviral effect of oxoquinoline 4h was more prominent than acyclovir which leads us to suggest compound 4h as a promising molecule for further anti-BoHV-5 drug design.
