- AGRICULTURAL CHEMICALS
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The present invention relates to picolinic acid derivatives that are useful in treating fungal diseases ofplants.
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Page/Page column 59; 108
(2019/08/08)
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- Synthesis, SAR and molecular docking study of novel non-β-lactam inhibitors of TEM type β-lactamase
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The novel classes of acylated phenoxyanilide and thiourea compounds were investigated for their ability to inhibit TEM type β-lactamase enzyme. Two compounds 4g and 5c reveal the inhibition potency in micromolar range and show their action by non-covalent binding in the vicinity of the TEM-171 active site. The structure activity relationship around carbon chain length and different substituents in ortho- and para-positions of acylated phenoxyanilide as well as molecular modelling study has been performed.
- Antipin, Roman L.,Beshnova, Daria A.,Petrov, Rostislav A.,Shiryaeva, Anna S.,Andreeva, Irina P.,Grigorenko, Vitaly G.,Rubtsova, Maya Yu.,Majouga, Alexander G.,Lamzin, Victor S.,Egorov, Alexey M.
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p. 1588 - 1592
(2017/03/17)
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- Structure-based design of N-substituted 1-hydroxy-4-sulfamoyl-2-naphthoates as selective inhibitors of the Mcl-1 oncoprotein
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Structure-based drug design was utilized to develop novel, 1-hydroxy-2-naphthoate-based small-molecule inhibitors of Mcl-1. Ligand design was driven by exploiting a salt bridge with R263 and interactions with the p2 pocket of the protein. Significantly, target molecules were accessed in just two synthetic steps, suggesting further optimization will require minimal synthetic effort. Molecular modeling using the Site-Identification by Ligand Competitive Saturation (SILCS) approach was used to qualitatively direct ligand design as well as develop quantitative models for inhibitor binding affinity to Mcl-1 and the Bcl-2 relative Bcl-xL as well as for the specificity of binding to the two proteins. Results indicated hydrophobic interactions in the p2 pocket dominated affinity of the most favourable binding ligand (3bl: Ki = 31 nM). Compounds were up to 19-fold selective for Mcl-1 over Bcl-xL. Selectivity of the inhibitors was driven by interactions with the deeper p2 pocket in Mcl-1 versus Bcl-xL. The SILCS-based SAR of the present compounds represents the foundation for the development of Mcl-1 specific inhibitors with the potential to treat a wide range of solid tumours and hematological cancers, including acute myeloid leukemia.
- Lanning, Maryanna E.,Yu, Wenbo,Yap, Jeremy L.,Chauhan, Jay,Chen, Lijia,Whiting, Ellis,Pidugu, Lakshmi S.,Atkinson, Tyler,Bailey, Hala,Li, Willy,Roth, Braden M.,Hynicka, Lauren,Chesko, Kirsty,Toth, Eric A.,Shapiro, Paul,MacKerell, Alexander D.,Wilder, Paul T.,Fletcher, Steven
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p. 273 - 292
(2016/03/22)
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- Discovery of 1,2,4-triazole-1,3-disulfonamides as dual inhibitors of mitochondrial complex II and complex III
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Respiratory chain succinate-ubiquinone oxidoreductase (SQR or complex II) and ubihydroquinone-cytochrome (cyt) c oxidoreductase (cyt bc1 or complex III) have been demonstrated as the promising targets of numerous antibiotics and fungicides. As a continuation of our research work on the development of new fungicides, a series of 1,2,4-triazole-1,3-disulfonamide derivatives with dual functions targeting both SQR and cyt bc1 were designed and synthesized by coupling diverse diphenyl ether moieties with triazolesulfonamide units. These newly synthesized compounds were characterized by elemental analyses, 1H NMR and ESI-MS spectrometry. The in vitro assay indicated that most of the synthesized compounds displayed good inhibition against porcine succinate-cytochrome reductase (SCR) with IC50 values ranging from 3.2 to 81.8 μM, revealing much higher activity than that of the commercial control amisulbrom whose IC50 value is 93.0 μM. Further evaluation against the respective SQR and cyt bc1 indicated that most compounds exhibited SQR-inhibiting activity as well as cyt bc1-inhibiting activity, but the inhibition potency against SQR is much higher than that against cyt bc1, showing that the SCR inhibition might be contributed greatly by the SQR inhibition. The further antibacterial evaluation against Xanthomonas oryzae pv. oryzae revealed that four compounds showed excellent potency at the concentration of 20 μg mL-1. In particular, compounds 6h and 6j exhibited much better antibacterial activity than the commercial control bismerthiazol in terms of their EC50. Impressively, 6j has an EC90 of 33.62 μg mL-1, more than 10-fold higher than that of bismerthiazol.
- Cheng, Hua,Shen, Yan-Qing,Pan, Xia-Yan,Hou, Yi-Ping,Wu, Qiong-You,Yang, Guang-Fu
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p. 7281 - 7292
(2015/09/02)
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- Metabolism of nitrodiphenyl ether herbicides by dioxin-degrading bacterium Sphingomonas wittichii RW1
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Nitrodiphenyl ether herbicides, including chlomethoxyfen, nitrofen, and oxyfluorfen are potent herbicides. Some metabolites and parent compounds are considered as possible mutagens and endocrine disruptors. Both properties pose serious hygienic and environmental risks. Sphingomonas wittichii RW1 is a well-known degrader of polychlorinated dibenzo-p-dioxins, dibenzofurans, and diphenyl ethers. However, no detailed research of its metabolic activity has been performed against pesticides with a diphenyl ether scaffold. In this study, we report S. wittichii RW1 as a very potent diphenyl ether herbicide- metabolizing bacterium with broad substrate specificity. The structures of metabolites were determined by instrumental analysis and synthetic standards. Most pesticides were rapidly removed from the culture medium in the order of nitrofen > oxyfluorfen > chlomethoxyfen. In general, herbicides were degraded through the initial reduction and N-acetylation of nitro groups, followed by ether bond cleavage. Relatively low concentrations of phenolic and catecholic metabolites throughout the study suggested that these metabolites were rapidly metabolized and incorporated into primary metabolism. These results indicate that strain RW1 has very versatile metabolic activities over a wide range of environmental contaminants.
- Young, Soo Keum,Young, Ju Lee,Kim, Jeong-Han
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experimental part
p. 9146 - 9151
(2010/04/23)
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- Heterocyclic compounds
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A herbicidal compound of formula (I): in which R1 is independently selected from H, CN, NO2, halogen, lower alkyl, lower haloalkyl; m is an integer of from 1 to 4; R2 is N or CR1 where R1 is as defined above; R3 is a group of formula (a), (b) or (c): or N-oxide or quaternary salt derivatives thereof wherein R4 is a specified organic group. Processes for the preparation of these compounds and compositions containing them are also described.
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- Glycosides of N-Hydroxy-N-arylamine Derivatives. Part 3. Kinetic and Mechanistic Studies on the Degradation Reaction of O-Glycosides of N-Hydroxy-N-arylamines and their Acetohydroxamic Acids in Acidic and Alkaline Media
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Good first-order kinetics of the degradation reaction of 1--1-deoxy-β-D-glucopyranoses (1a-d), 1-(N-arylamino)oxy-1-deoxy-β-D-glucopyranose (2a) and sodium 1--1-deoxy-β-D-glucopyranuronate (3a) in aqueous acidic solutions have been observed.Compounds (1a-d) and (3a) were fairly stable in neutral solution, but in aqueous acidic solutions at 20 deg C these compounds decomposed to the corresponding arylamino derivatives (4a-d) and D-gluconic acid (5) .The compound (2a) decomposed ca. 7400 times faster than compound (1a) to the same products (4a) and (5) in the same conditions.In an alkaline solution, compounds (1a)-(3a) gave the corresponding azoxybenzene.In the acid-catalysed redox degradation reaction, the hydrolysis of the N-acetyl group of compounds (1a-d) and (3a) is considered to be the rate-determining step.The effects of pH and additives on the reaction rate are reported.The mechanism of the acid-catalysed redox fission of the N-O linkage in the above O-glycosides is discussed.
- Yoshioka, Tadao,Uematsu, Takayoshi
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p. 1377 - 1382
(2007/10/02)
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