2790-97-8Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of hydroxamic acid-substituted 2,4-diaryl aminopyrimidines as potent EGFRT790M/L858R inhibitors for the treatment of NSCLC
Chen, Lixue,Li, Lei,Li, Yanxia,Ma, Xiaodong,Meng, Qiang,Qi, Yan,Sun, Hunjun,Tang, Zeyao,Wang, Changyuan,Xu, Youjun,Zhang, Yunhao
, (2021/07/14)
A series of 2,4-diarylaminopyrimidine derivatives bearing hydrophilic hydroxamic acids were designed and synthesized as potent EGFRT790M/L858R inhibitors. Among the derivatives synthesized, 10c (IC50 = 5.192 nM), 10j (IC50 = 10.35 nM), and 10o (IC50 = 0.3524 nM) exhibited higher potencies against EGFRT790/M/L858R compared to the known EGFR inhibitor AZD-9291 (IC50 = 20.80 nM). Moreover, 10j showed moderate activity against H1975 cells transfected with the EGFRT790M/L858R mutant, with an IC50 of 0.2113 μM over A431 (wild-type EGFR, SI = 47.3). In addition, 10j exhibited low toxicity in normal HBE cells (human bronchial epithelial cells, IC50 > 40 μΜ). Analysis of the mode of action indicated that 10j effectively induced apoptosis in H1975 cells by arresting the cells in the G2/M phase. Compound 10j also demonstrated efficacy in inhibiting tumor growth in a H1975 xenograft mouse model without losing body weight or killing the mice. Taken together, these results suggested that 10j might be a promising candidate for development as a potential treatment for NSCLC harboring the EGFRT790M/L858R mutation.
Synthesis and anticonvulsant activity of some 2/3- benzoylaminopropionanilide derivatives
Uysal,Calis,Soyer
experimental part, p. 295 - 300 (2012/08/07)
In this study, the synthesis and anticonvulsant properties of sixteen 2/3-benzoylaminopropionanilide derivatives were described. Molecular design of the compounds has been based on the modification of lacosamide which is a functionalized amino acid with a novel anticonvulsant activity. The structural confirmation of the title compounds was achieved by spectral and analytical data. The anticonvulsant activity profile of synthesized compounds was determined by maximal electroshock (MES) and subcutaneous metrazole (scMet) seizure tests, whereas their neurotoxicity was examined using rotarod test. All these tests were performed in accordance with the procedures of the Antiepileptic Drug Development (ADD) program. The majority of the compounds were effective in the MES or scMet screening tests. None of the compounds showed neurotoxicity according to the rotarod test at studied doses. Most active compounds in the series were 3, 12 and 13, which bearing 2-methyl, 2-ethyl and 2-isopropyl substituent on the N-phenyl ring, respectively. Georg Thieme Verlag KG Stuttgart - New York.
Synthesis and biological screening of novel derivatives of 3-(N-substituted carboxamidoethylthio)-(4H)-1,2,4-triazoles
Manikrao, Anil M.,Fursule, Ravindra A.,Rajesh,Kunjwani, Harish K.,Sabale, Prafulla M.
experimental part, p. 1642 - 1647 (2011/03/17)
3-Mercapto-(4H)-1,2,4-triazole has been synthesized from 1-formylthiosemicarbazide. Different N-substituted β-chloropropionamides have been prepared by reacting substituted amines with β- chloropropionylchloride. Different Nsubstituted β-chloropropionamides have been condensed with 3-mercapto-(4H)-1,2,4-triazole in basic medium to obtain various 3-(N-substituted carboxamidoethylthio)-(4H)-1,2,4-triazoles. The structure of the synthesized compounds are confirmed by IR, 1H NMR spectra and elemental analysis. All the compounds have been screened for their analgesic, anti-inflammatory and anxiolytic activity.
Synthesis and anticonvulsant activity of some ω-(1H-1-imidazolyl)-N- phenylalkanoic acid amide derivatives
Aktuerk, Zeynep,Kilic, Fatma,Erol, Kevser,Pabuccuoglu, Varol
, p. 201 - 206 (2007/10/03)
In this study, 15 ω-(1H-imidazol-1-yl)-N-phenylacetamide, propionamide and butyramide derivatives having methoxyl, methyl, nitro and chloro in ortho position of N-phenyl ring or without any substituent have been realized by two-step synthesis. Their antic
