4260-28-0Relevant academic research and scientific papers
Metal-free C-H methylation and acetylation of heteroarenes with PEG-400
Kudale, Vishal Suresh,Wang, Jeh-Jeng
, p. 3506 - 3511 (2020/06/25)
The generation of a methyl carbon source from renewable and cheap sources is challenging. Herein, we describe a novel and an efficient route for methylation and acetylation of aza-heteroarenes using PEG-400 under O2and TsOH·H2O for the first time by tuning the reaction conditions using a different set of starting materials. The key features of the current protocol are oxidative C-O and C-C bond scission under metal-free conditions with good functional group tolerance, and a broad substrate scope. The potential applicability of the designed methodology was demonstrated for the synthesis of central nervous system (CNS) depressant and anticonvulsant drug molecules by a one-pot strategy.
Styryl quinazolinones as potential inducers of myeloid differentiation via upregulation of C/EBPα
Sridhar, Radhakrishnan,Takei, Hisashi,Syed, Riyaz,Kobayashi, Ikei S.,Hui, Liu Bee,Kamal, Ahmed,Tenen, Daniel G.,Kobayashi, Susumu S.
, (2018/09/06)
The CCAAT enhancer-binding protein α (C/EBPα) plays an important role in myeloid cell differentiation and in the enhancement of C/EBPα expression/activity, which can lead to granulocytic differentiation in acute myeloid leukemia (AML) cells. We found that styryl quinazolinones induce upregulation of C/EBPα expression, and thereby induce myeloid differentiation in human myeloid leukemia cell lines. We screened a series of active styryl quinazolinones and evaluated the structure–activity relationship (SAR) of these small molecules in inducing C/EBPα expression—thereby prompting the leukemic cells to differentiate. We observed that compound 78 causes differentiation at 3 μM concentration, while 1 induces differentiation at 10 μM concentration. We also observed an increase in the expression of neutrophil differentiation marker CD11b upon treatment with 78. Both the C/EBPα and C/EBPε levels were found to be upregulated by treatment with 78. These SAR findings are inspiration to develop further modified styryl quinazolinones, in the path of this novel differentiation therapy, which can contribute to the care of patients with AML.
Atropisomeric quinazolin-4-one derivatives are potent noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists
Welch,Ewing,Huang,Menniti,Pagnozzi,Kelly,Seymour,Guanowsky,Guhan,Guinn,Critchett,Lazzaro,Ganong,DeVries,Staigers,Chenard
, p. 177 - 181 (2007/10/03)
Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure-activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated. Separation of these atropisomers resulted in the identification of (+)-38 (CP-465,022), a compound that binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity.
Synthesis and Anticonvulsant Activity of Some New 2-Substituted 3-Aryl-4(3H)-quinazolinones
Wolfe, James F.,Rathman, Terry L.,Sleevi, Mark C.,Campbell, James A.,Greenwood, Thomas D.
, p. 161 - 166 (2007/10/02)
A series of 4(3H)-quinazolinones structurally related to 2-methyl-3-o-tolyl-4(3H)-quinazolinone (methaqualone, 3) were synthesized and evaluated for anticonvulsant activity.Preliminary screening of these compounds revealed that 2--3-aryl-4(3H)-quinazolinones 6l and 8i, 8k, and 8p-r having a single ortho substituent on the 3-aryl group had the most promising anticonvulsant activity.Compounds 6l and 8i possessing 3-o-tolyl and 3-o-chlorophenyl groups, respectively, showed good protection against MES- and scMet-induced seizures, combined with relatively low neurotoxicity after intraperitoneal administration in mice.They also exhibited low toxicity in tests for determining the mean hypnotic dose (HD50) and the median lethal dose (LD50).Although these compounds were markedly more potent as anticonvulsants when administered orally in mice and rats, they were also more neurotoxic.This neurotoxicity was particularly acute in oral tests with rats. which resulted in marginal protective indices.In drug differentiation tests, compound 6l was ineffective against seizures induced by bicuculline, picrotoxin, and strychnine, while 8i showed some protection against picrotoxin-induced seizures.
