10394-67-9Relevant academic research and scientific papers
Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study
He, Haifeng,Xia, Hongying,Xia, Qin,Ren, Yanliang,He, Hongwu
, p. 5652 - 5661 (2017/10/09)
By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel ‘open-chain’ classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1–23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC50 = 0.15–23.55 μM). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC50 values of 0.60, 0.15, 0.39 and 0.34 μM against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E.coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide.
Synthesis and biological evaluation of substituted 2-anilino-7H- pyrrolopyrimidines as PDK1 inhibitors
O'Brien, Nathan J.,Brzozowski, Martin,Wilson, David J.D.,Deady, Leslie W.,Abbott, Belinda M.
, p. 4947 - 4956 (2014/07/07)
An efficient and scalable route for a series of novel substituted 2-anilino-7H-pyrrolopyrimidine compounds as potential inhibitors of PDK1, an important regulator of the PI3K/Akt pathway that is dysregulated in many cancers, was developed and is described. The synthetic strategy was designed around Suzuki and Buchwald-Hartwig cross-couplings of a boronate fragment and various customised anilines sequentially with 2,4-dichloro-7-tosyl-7H- pyrrolopyrimidine. All fragments were constructed separately and cross-coupled to provide access to a range of novel compounds. Biological evaluation of these was undertaken, with modest inhibition observed.
Metal-free transfer hydrogenation of nitroarenes in water with vasicine: Revelation of organocatalytic facet of an abundant alkaloid
Sharma, Sushila,Kumar, Manoranjan,Kumar, Vishal,Kumar, Neeraj
, p. 9433 - 9439 (2014/12/11)
Vasicine, an abundantly available quinazoline alkaloid from the leaves of Adhatoda vasica, has been successfully employed for metal- and base-free reduction of nitroarenes to the corresponding anilines in water. The method is chemoselective and tolerates a wide range of reducible functional groups, such as ketones, nitriles, esters, halogens, and heterocyclic rings. Dinitroarenes reduced selectively to the corresponding nitroanilines under the present reaction conditions.
Zinc phthalocyanine with PEG-400 as a recyclable catalytic system for selective reduction of aromatic nitro compounds
Sharma, Upendra,Kumar, Neeraj,Verma, Praveen Kumar,Kumar, Vishal,Singh, Bikram
supporting information; experimental part, p. 2289 - 2293 (2012/09/10)
Zinc phthalocyanine with PEG-400 was established as a catalytic system for chemo and regioselective reduction of aromatic nitro compounds to corresponding amines. A large range of reducible functional groups such as acid, amide, ester, halogen, lactone, nitrile, N-benzyl, O-benzyl, hydroxy and heterocycles were well tolerated. Direct synthesis of benzotriazole from O-dinitrobenzene was achieved for the first time. The present catalytic system was successfully employed for the reduction of carbonyl and ester compounds to corresponding alcohols and reductive amination of benzaldehydes with primary amines to form corresponding secondary amines. Remarkable advantages of the present catalytic method include low loading of metal, avoidance of toxic ligands and high isolated yields. The catalyst was recyclable up to four times without any loss of selectivity and activity.
New anti-viral drugs for the treatment of the common cold
Maugeri, Caterina,Alisi, Maria A.,Apicella, Claudia,Cellai, Luciano,Dragone, Patrizia,Fioravanzo, Elena,Florio, Saverio,Furlotti, Guido,Mangano, Giorgina,Ombrato, Rosella,Luisi, Renzo,Pompei, Raffaello,Rincicotti, Vito,Russo, Vincenzo,Vitiello, Marco,Cazzolla, Nicola
, p. 3091 - 3107 (2008/09/20)
Human Rhinovirus (HRV) is the most important aetiologic agent of common cold in adults and children. HRV is a single-stranded, positive sense RNA virus and, despite the high level of conservation among different serotypes, sequence alignment of viral protease 3C with mammalian protease reveals no homology. Thus, protease 3C is an optimal target for the development of anti-HRV agents. In the present work we investigated the design, the synthesis and the development of new potential reversible inhibitors against HRV protease 3C. Docking studies on the crystallized structure of HRV2 protease 3C led us to the design and the synthesis of a series of 3,5 disubstituted benzamides able to act as analogues of the substrate. We also developed 1,3,5 trisubstituted benzamides where aromatic substitutions on the aryl ring led us to investigate the importance of π-π interaction on the stabilization of protease 3C-inhibitor complex. All structures were tested for enzymatic inhibition on HRV14 protease 3C. Results highlighted the inhibitory activity of compounds 13, 14, and 20 (91%, 81%, and 85% at 10 μM, respectively), with the latter exhibiting an ID50 (dose that inhibits 50% of the viral cytopathic effect) on HRV-14 = 25 μg/ml.
Calix[3]amides - Bowl-shaped cyclic trimers toward building block for molecular recognition: Self-complementary dimeric structure in the crystal
Imabeppu, Fumiaki,Katagiri, Kosuke,Masu, Hyuma,Kato, Takako,Tominaga, Masahide,Therrien, Bruno,Takayanagi, Hiroaki,Kaji, Eisuke,Yamaguchi, Kentaro,Kagechika, Hiroyuki,Azumaya, Isao
, p. 413 - 416 (2007/10/03)
Bowl-shaped cyclic trimers of aromatic amides were simply synthesized in high yield by condensation reaction of meta-substituted 3-(alkylamino)benzoic acid using dichlorotriphenylphosphorane. The cyclic amides exist in syn conformation, which has a small chiral cavity, and a pair of each enantiomeric conformer formed a dimeric structure in the crystal.
Neuroprotective small organic molecules, compositions and uses related thereto
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Page/Page column sheet 5; 44, (2008/06/13)
The present application is directed to therapeutic compounds, compositions, and methods for culturing neuronal cells and for preventing and the treatment of neurodegenerative diseases, such as Parkinson's disease and amyotrophic lateral sclerosis (ALS).
