- Design, synthesis and pharmacological screening of novel renoprotective methionine-based peptidomimetics: Amelioration of cisplatin-induced nephrotoxicity
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Cisplatin (CP) is an effective chemotherapeutic agent for treatment of various types of cancer, however efforts are needed to reduce its toxic side effect. Previous studies revealed promising effect of peptides in decreasing CP induced nephrotoxicity. Herein, novel Met-based peptidomimetics were synthesized using N-acylbenzotriazole as acylating agent in high yield. Evaluation of renoprotective effect of the synthesized targets on CP treated kidney cell line (LLC-PK1) revealed that pretreatment with 1/3 IC50 of targets II, IIIa-g attenuated CP induced cell death where the IC50 of CP was raised from 3.28 μM to 9.25-41.1 μM. The most potent compounds IIIg, II and IIIb exhibited antioxidative stress in CP-treated LLC-PK1 cells as confirmed by raising GSH/GSSG ratio and SOD concentration as well as decreasing ROS and MDA. Additionally, in vivo experiments using Sprague Dawley rats showed renoprotective effect of IIIg against CP-induced nephrotoxicity as evidenced by improved results of renal function tests and attenuated CP-induced renal structural injury. Moreover, antioxidant activity of IIIg was demonstrated via its ability to reduce renal MDA level and up-regulate renal antioxidant element GSH level. Further, immunohistochemistry of renal specimens showed the ability of IIIg to restore CP-induced suppression of Nrf2. Interestingly, in vivo and in vitro studies demonstrated that IIIg had no effect on CP antiproliferative activity. An assessment of the ADMET properties revealed that targets IIIg, II and IIIb showed good drug-likeness in terms of their physicochemical, pharmacokinetic properties. The findings presented here showcase that IIIg is a promising renoprotective candidate with antioxidative stress potential.
- Agha, Khalid A.,Ibrahim, Tarek S.,Elsherbiny, Nehal M.,El-Sherbiny, Mohamed,Abdel-Aal, Eatedal H.,Abdel-Samii, Zakaria K.,Abo-Dya, Nader E.
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- N -Acylbenzotriazoles as Proficient Substrates for an Easy Access to Ureas, Acylureas, Carbamates, and Thiocarbamates via Curtius Rearrangement Using Diphenylphosphoryl Azide (DPPA) as Azide Donor
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A diverse range of ureas, N -acylureas, carbamates, and thiocarbamates has been synthesized in good to excellent yields by reacting N -acylbenzotriazoles individually with amines or amides or phenols or thiols in the presence of diphenylphosphoryl azide (DPPA) as a suitable azide donor in anhydrous toluene at 110 °C for 3-4 hours. In this route, DPPA was found to be a good alternative to trimethylsilyl azide and sodium azide for the azide donor in Curtius degradation. The high reaction yields, one-pot and metal-free conditions, straightforward nature, easy handling, use of readily available reagents, and in many cases avoidance of column chromatography are the notable features of the devised protocol.
- Yadav, Mangal S.,Singh, Sumt K.,Agrahari, Anand K.,Singh, Anoop S.,Tiwari, Vinod K.
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p. 2494 - 2502
(2021/03/26)
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- Ruthenium-Catalyzed Reductive Arylation of N-(2-Pyridinyl)amides with Isopropanol and Arylboronate Esters
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A new three-component reductive arylation of amides with stable reactants (iPrOH and arylboronate esters), making use of a 2-pyridinyl (Py) directing group, is described. The N-Py-amide substrates are readily prepared from carboxylic acids and PyNH2, and the resulting N-Py-1-arylalkanamine reaction products are easily transformed into the corresponding chlorides by substitution of the HN-Py group with HCl. The 1-aryl-1-chloroalkane products allow substitution and cross-coupling reactions. Therefore, a general protocol for the transformation of carboxylic acids into a variety of functionalities is obtained. The Py-NH2 by-product can be recycled.
- Ronson, Thomas O.,Renders, Evelien,Van Steijvoort, Ben F.,Wang, Xubin,Wybon, Clarence C. D.,Prokopcová, Hana,Meerpoel, Lieven,Maes, Bert U. W.
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supporting information
p. 482 - 487
(2019/01/04)
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- An Improved N-Acylation of 1 H-Benzotriazole Using 2,2′-Dipyridyl?-di?-sulfide and Triphenylphosphine
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A novel path has been developed for the conversion of carboxylic acids into the corresponding N-acylbenzotriazoles by using 2,2′-dipyridyl disulfide/PPh 3 in anhydrous dichloromethane in the presence of 1 H-benzotriazole. Mild reaction conditio
- Singh, Anoop S.,Agrahari, Anand K.,Mishra, Nidhi,Singh, Mala,Tiwari, Vinod K.
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p. 470 - 476
(2019/01/10)
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- Trichloroisocyanuric Acid Mediated High-Yielding Synthesis of N -Acylbenzotriazoles under Mild Reaction Conditions
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N -Acylbenzotriazoles are achieved in good yields from the corresponding carboxylic acids by using only 0.35 equivalent of trichloroisocyanuric acid and 1.2 equivalents of PPh 3. The salient features of the developed reaction path include an ec
- Singh, Mala,Singh, Anoop S.,Mishra, Nidhi,Agrahari, Anand K.,Tiwari, Vinod K.
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p. 2183 - 2190
(2019/05/10)
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- Visible-Light-Induced C(sp2)-P Bond Formation by Denitrogenative Coupling of Benzotriazoles with Phosphites
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A visible-light-induced denitrogenative phosphorylation of benzotriazoles is presented, in which diverse substituted aryl phosphonates could be obtained in good to excellent yields. This efficient protocol exhibits good tolerance with various functional g
- Jian, Yong,Chen, Ming,Huang, Binbin,Jia, Wei,Yang, Chao,Xia, Wujiong
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supporting information
p. 5370 - 5374
(2018/09/13)
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- A new methodology for the synthesis of N-acylbenzotriazoles
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A facile and economic path for an easy access of diverse N-acylbenzotriazoles from carboxylic acid has been devised using NBS/PPh3 in anhydrous dichloromethane. High yield of product was obtained at room temperature in one hour reaction time under mild reaction conditions.
- Singh, Anoop S.,Agrahari, Anand K.,Singh, Mala,Mishra, Nidhi,Tiwari, Vinod K.
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- A Biocatalytic Route to Highly Enantioenriched β-Hydroxydioxinones
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A novel biocatalytic system to access a wide variety of β-hydroxydioxinones from β-ketodioxinones employing commercial engineered ketoreductases has been developed. This practical system provides a remarkably straightforward solution to limitations in acc
- Betori, Rick C.,Miller, Eric R.,Scheidt, Karl A.
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supporting information
p. 1131 - 1137
(2017/04/11)
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- An efficient one-pot synthesis of: N, N ′-disubstituted ureas and carbamates from N -acylbenzotriazoles
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A facile and high-yielding one-pot synthesis of carbamates and N,N′-disubstituted symmetrical ureas from N-acylbenzotriazoles has been devised. It is believed that, the intermediate acyl-azide undergo Curtius rearrangement and in different solvents gives different products i.e. carbamates in alcohols and N,N′-disubstituted symmetrical urea in THF.
- Singh, Anoop S.,Kumar, Dhananjay,Mishra, Nidhi,Tiwari, Vinod K.
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p. 84512 - 84522
(2016/10/12)
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- TCT-mediated synthesis of N-acylbenzotriazoles in aqueous media
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The synthesis of N-acylbenzotriazoles has been demonstrated by the 2,4,6-trichloro-1,3,5-triazine (TCT)-mediated condensation of carboxylic acids with 1H-benzotriazole in aqueous media. In saturated aqueous sodium bicarbonate, TCT was found to be relatively stable and functioned as an efficient acid activator in the acyl transfer process. This operationally simple and economic method allows the scalable synthesis of N-acylbenzotriazoles in good to excellent yields.
- Wet-Osot, Sirawit,Phakhodee, Wong,Pattarawarapan, Mookda
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p. 6998 - 7000
(2015/11/27)
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- Facile synthesis of N-acylbenzotriazoles from carboxylic acids mediated by 2,4,6-trichloro-1,3,5-triazine and triethylamine
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Abstract A facile, efficient, and economic method toward N-acylbenzotriazoles was reported using 2,4,6-trichloro-1,3,5-triazine in combination with triethylamine as a carboxylic acid activator. Through reacting 1H-benzotriazole with the generated triacylated triazine intermediate, a series of N-acylbenzotriazoles could be rapidly prepared in high yields without column chromatography.
- Wet-Osot, Sirawit,Duangkamol, Chuthamat,Pattarawarapan, Mookda,Phakhodee, Wong
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p. 959 - 963
(2015/02/19)
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- Acyloxyphosphonium versus aminophosphonium intermediates: Application to the synthesis of N-acylbenzotriazoles
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In attempts to convert carboxylic acids directly into N-acylbenzotriazoles by using Ph3P/I2 as an acid-activating system, the outcome of the reaction is reversed from no reaction to almost quantitative yield of the expected product simply by switching the order of the addition of the reagents to the presumed acyloxyphosphonium intermediate. If triethylamine was present before treatment with 1H-benzotriazole, anhydride was always exclusively generated without a detectable amount of the expected product. However, if the base was applied after the addition of 1H-benzotriazole, the reaction proceeded smoothly to afford N-acylbenzotriazoles in good to excellent yields within short reaction times. 31P NMR spectroscopy revealed the presence of a benzotriazophosphonium species in preventing the formation of the anhydride by attack of the carboxylate anion at the acyl function of the acyloxyphosphonium salt.
- Duangkam Ol, Chuthamat,Wangngae, Sirilak,Pattarawarapan, Mookda,Phakhodee, Wong
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supporting information
p. 7109 - 7112
(2015/02/19)
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- Synthesis and structure-activity relationship studies of cytotoxic anhydrovinblastine amide derivatives
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A series of 3-demethoxycarbonyl-3-amide methyl anhydrovinblastine derivatives (5b-24b) was designed, synthesized, and evaluated for their proliferation inhibition activities against two tumor cell lines (A549 and HeLa). Most of the amide anhydrovinblastin
- Shao, Yong,Zhang, Han-Kun,Ding, Hong,Quan, Hai-Tian,Lou, Li-Guang,Hu, Li-Hong
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experimental part
p. 1170 - 1177
(2011/03/20)
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- Synthesis and structure-activity relationship studies of cytotoxic ester and ether anhydrovinblastine derivatives
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Two new series of 3-demethoxycarbonyl-3-ester and 3-demethoxycarbonyl-3- ether methyl anhydrovinblastine derivatives were designed, synthesized, and evaluated for their inhibitory activities against human non-small-cell lung cancer (A549) and cervical epi
- Zhang, Han-Kun,Shao, Yong,Ding, Hong,Hu, Li-Hong
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experimental part
p. 1669 - 1676
(2009/07/11)
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- Gas-phase thermolysis of benzotriazole derivatives. Part 3: Kinetic and mechanistic evidence for biradical intermediates in pyrolysis of aroylbenzotriazoles and related compounds
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Gas-phase pyrolysis (static and FVP) of 1-aroylbenzotriazoles gave the corresponding substituted benzoxazole, benzimidazole, benzamide, N-phenylbenzamide, phenanthridin-6(5H)-one derivatives and 1- cyanocyclopentadiene. The present kinetic and mechanistic findings also provide further evidence of the involvement of biradical or carbene reactive intermediates in the reaction pathway of gas-phase pyrolysis of benzotriazoles.
- Al-Awadi, Nouria A.,George, Bobby J.,Dib, Hicham H.,Ibrahim, Maher R.,Ibrahim, Yehia A.,El-Dusouqui, Osman M. E.
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p. 8257 - 8263
(2007/10/03)
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- Facile Syntheses of Oxazolines and Thiazolines with N-Acylbenzotriazoles under Microwave Irradiation
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Microwave reactions of 2-amino-2-methyl-1-propanol (2) or 2-aminoethanethiol hydrochloride (4) with readily available N-acylbenzotriazoles 1a-j in the presence of SOCl2 produced 2-substituted 2-oxazolines 3a-j in 84-98% yields and 2-substituted
- Katritzky, Alan R.,Cai, Chunming,Suzuki, Kazuyuki,Singh, Sandeep K.
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p. 811 - 814
(2007/10/03)
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- Hypervalent iodine in synthesis. 65: A new route to synthesize N-acylbenzotriazoles via palladium catalyzed carbonylation of benzotriazole and hypervalent iodonium salts in the presence of carbon monoxide
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N-acylbenzotriazoles are obtained directly in fair yields by palladium-catalyzed carbonylation of diaryliodonium salts with benzotriazoles in the presence of carbon monoxide.
- Wang,Chen
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p. 1633 - 1637
(2007/10/03)
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- N-acylbenzotriazoles: Neutral acylating reagents for the preparation of primary, secondary, and tertiary amides
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Readily available N-acylbenzotriazoles 2a-q efficiently acylate aqueous ammonia and primary and secondary amines to give primary, secondary, and tertiary amides in good to excellent yields. The wide applicability of the procedure is illustrated by the preparation of (i) α-hydroxyamides from α-hydroxy acids and of (ii) perfluoroalkylated amides.
- Katritzky,He,Suzuki
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p. 8210 - 8213
(2007/10/03)
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