164522-90-1Relevant articles and documents
Pyrimidine onium compound and application thereof
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Paragraph 0286-0289, (2019/10/23)
The invention relates to a pyrimidine onium compound, nitride oxides, salt of the nitride oxides and a composition comprising the compound. The invention further relates to an application of the compound to plant pest control.
Natural Product Neopeltolide as a Cytochrome bc1 Complex Inhibitor: Mechanism of Action and Structural Modification
Zhu, Xiao-Lei,Zhang, Rui,Wu, Qiong-You,Song, Yong-Jun,Wang, Yu-Xia,Yang, Jing-Fang,Yang, Guang-Fu
, (2019/03/19)
The marine natural product neopeltolide was isolated from a deep-water sponge specimen of the family Neopeltidae. Neopeltolide has been proven to be a new type of inhibitor of the cytochrome bc1 complex in the mitochondrial respiration chain. However, its detailed inhibition mechanism has remained unknown. In addition, neopeltolide is difficult to synthesize because of its very complex chemical structure. In the present work, the binding mode of neopeltolide was determined for the first time by integrating molecular docking, molecular dynamics simulations, and molecular mechanics Poisson-Boltzmann surface area calculations, which showed that neopeltolide is a Qo site inhibitor of the bc1 complex. Then, according to guidance via inhibitor-protein interaction analysis, structural modification was carried out with the aim to simplify the chemical structure of neopeltolide, leading to the synthesis of a series of new neopeltolide derivatives with much simpler chemical structures. The calculated binding energies (ΔGcal) of the newly synthesized analogues correlated very well (R2 = 0.90) with their experimental binding free energies (ΔGexp), which confirmed that the computational protocol was reliable. Compound 45, bearing a diphenyl ether fragment, was successfully designed and synthesized as the most potent candidate (IC50 = 12 nM) against porcine succinate cytochrome c reductase. The molecular modeling results indicate that compound 45 formed a π-π interaction with Phe274 and two hydrogen bonds with Glu271 and His161. The present work provides a new starting point for future fungicide discovery to overcome the resistance that the existing bc1 complex inhibitors are facing.
A 2,2′-bipyridine-palladacycle catalyzed the coupling of arylboronic acids with nitroarenes
Peng, Dongpo,Yu, Ajuan,Wang, Hailei,Wu, Yangjie,Chang, Junbiao
, p. 6884 - 6889 (2013/07/26)
A novel palladium-catalyzed protocol for the synthesis of diaryl ethers derivatives has been developed. In the presence of 2,2′-bipyridine- cyclopalladated ferrocenylimine complex (Cat. Ic), diaryl ethers were selectively generated by adjusting reaction parameters through the coupling of arylboronic acids and nitroarenes with yields ranging from poor to good. The efficiency of this reaction was demonstrated by its compatibility with a range of groups. Moreover, the rigorous exclusion of air or moisture was not required in these transformations.
Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials
Yeates, Clive L.,Batchelor, John F.,Capon, Edward C.,Cheesman, Neil J.,Fry, Mitch,Hudson, Alan T.,Pudney, Mary,Trimming, Helen,Woolven, James,Bueno, José M.,Chicharro, Jesús,Fernández, Esther,Fiandor, José M.,Gargallo-Viola, Domingo,De Las Heras, Federico Gómez,Herreros, Esperanza,León, María L.
, p. 2845 - 2852 (2008/12/23)
A series of diaryl ether substituted 4-pyridones have been identified as having potent antimalarial activity superior to that of chloroquine against Plasmodium falciparum in vitro and murine Plasmodium yoelii in vivo. These were derived from the anticoccidial drug clopidol through a systematic study of the effects of varying the side chain on activity. Relative to clopidol the most active compounds show > 500-fold improvement in IC50 for inhibition of P. falciparum in vitro and about 100-fold improvement with respect to ED50 against P. yoelii in mice. These compounds have been shown elsewhere to act selectively by inhibition of mitochondrial electron transport at the cytochrome bc1 complex.
Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles
Arienti, Kristen L.,Brunmark, Anders,Axe, Frank U.,McClure, Kelly,Lee, Alice,Blevitt, Jon,Neff, Danielle K.,Huang, Liming,Crawford, Shelby,Pandit, Chennagiri R.,Karlsson, Lars,Breitenbucher, J. Guy
, p. 1873 - 1885 (2007/10/03)
The discovery of a series of novel, potent, and highly selective inhibitors of the DNA damage control kinase chk2 is disclosed. Here we report the first SAR study around inhibitors of this kinase. High-throughput screening of purified human chk2 led to the identification of a novel series of 2-arylbenzimidazole inhibitors of the kinase. Optimization was facilitated using homology models of chk2 and docking of inhibitors, leading to the highly potent 2-arylbenz-imidazole 2h (IC50 15 nM). Compound 2h is an ATP-competitive inhibitor of chk2 that dose dependency protects human CD4 + and CD8+ T-cells from apoptosis due to ionizing radiation. This work suggests that a selective small molecule inhibitor of chk2 could be a useful adjuvant to radiotherapy, increasing the therapeutic window of such treatment.
Inhibitors of squalene synthase and protein farnesyltransferase
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, (2008/06/13)
The present invention provides a compound of the formula STR1 or a pharmaceutically acceptable salt thereof, which are useful for inhibiting protein farnesyltransferase and the farnesylation of the oncogene protein Ras or inhibiting de novo squalene production resulting in the inhibition of cholesterol biosynthesis, processes for the preparation of the compounds of the invention in addition to intermediates useful in these processes, a pharmaceutical composition, and to methods of using such compounds.
(Aryloxy)aryl semicarbazones and related compounds: A novel class of anticonvulsant agents possessing high activity in the maximal electroshock screen
Dimmock, Jonathan R.,Puthucode, Ramanan N.,Smith, Jennifer M.,Hetherington, Mark,Quail, J. Wilson,Pugazhenthi, Uma,Lechler, Terry,Stables, James P.
, p. 3984 - 3997 (2007/10/03)
A number of (aryloxy)aryl semicarbazones and related compounds were synthesized and evaluated far anticonvulsant activities. After intraperitoneal injection to mice, the semicarbazones were examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and neurotoxicity (NT) screens. The results indicated that greater protection was obtained in the MES test than the scPTZ screen. Quantitation of approximately one-third of the compounds revealed an average protection index (PI, i.e. TD50/ED50) of approximately 9. After oral administration to rats, a number of compounds displayed significant potencies in the MES screen (ED50 of 1-5 mg/kg) accompanied by very high protection indices. In fact over half the compounds had PI figures of greater than 100, and two were in excess of 300. The compounds were essentially inactive in the scPTZ and NT screens after oral administration to rats. Various compounds displayed greater potencies and PI figures in the mouse intraperitoneal and rat oral screens than three reference clinically used drugs. The data generated supported a binding site hypothesis. Quantitative structure-activity relationships indicated a number of physicochemical parameters which contributed to activity in the MES screen. X-ray crystallography of five compounds suggested the importance of certain interatomic distances and bond angles for activity in the mouse and rat MES screens.
