- Synthesis of benzotriazoles derivatives and their dual potential as α-amylase and α-glucosidase inhibitors in vitro: Structure-activity relationship, molecular docking, and kinetic studies
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Benzotriazoles (4–6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7–40). The synthetic compounds (7–40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α-glucosidase and α-amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC50 values of 2.00–5.6 and 2.04–5.72 μM against α-glucosidase and α-amylase enzymes, respectively. The synthetic compounds were divided into two categories “A” and “B”, in order to understand the structure-activity relationship. Compounds 25 (IC50 = 2.41 ± 1.31 μM), (IC50 = 2.5 ± 1.21 μM), 36 (IC50 = 2.12 ± 1.35 μM), (IC50 = 2.21 ± 1.08 μM), and 37 (IC50 = 2.00 ± 1.22 μM), (IC50 = 2.04 ± 1.4 μM) with chloro substitution/s at aryl ring were found to be most active against α-glucosidase and α-amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α-amylase and non-competitive mode of inhibition against α-glucosidase enzyme.
- Hameed, Shehryar,Kanwal,Seraj, Faiza,Rafique, Rafaila,Chigurupati, Sridevi,Wadood, Abdul,Rehman, Ashfaq Ur,Venugopal, Vijayan,Salar, Uzma,Taha, Muhammad,Khan, Khalid Mohammed
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- Tert -Butyl nitrite mediated nitrogen transfer reactions: Synthesis of benzotriazoles and azides at room temperature
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A conversion of o-phenylenediamines into benzotriazoles was achieved at room temperature using tert-butyl nitrite. The optimized conditions are also well suited for the transformation of sulfonyl and acyl hydrazines into corresponding azides. This protocol does not require any catalyst or acidic medium. The desired products were obtained in excellent yields in a short span of time.
- Azeez, Sadaf,Chaudhary, Priyanka,Sureshbabu, Popuri,Sabiah, Shahulhameed,Kandasamy, Jeyakumar
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supporting information
p. 6902 - 6907
(2018/10/02)
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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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- 2 - (3-cyano-4-alkoxy) phenyl-4-substituted thiazole-5- formic acid class compound, composition and its preparation and use
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The invention relates to a 2-(3-cyano-4-alkoxy) phenyl-4-substituted thiazole-5-formic acid compound which has xanthine oxidase inhibitory activity and is shown in a general formula I, a composition and preparation methods thereof. The invention also relates to applications of the compound and the composition thereof to preparation of medicaments for treating and/or preventing hyperuricemia and gout diseases. In the formula I, R2 is substituted or unsubstituted phenyl or a substituted or unsubstituted heteroaromatic radical, R1 is a substitutive aliphatic group of a straight chain or a branched chain, substituted or unsubstituted alicyclic hydrocarbonyl or substituted or unsubstituted aryl alkyl and A is an oxygen atom, a sulfur atom or a nitrogen atom.
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Paragraph 0164
(2016/10/07)
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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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- Synthesis, Characterization and Energetic Properties of 1,3,4-Oxadiazoles
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An efficient cyclization between nitro-substituted benzoic acids and nitro-substituted benzohydrazides affords 1,3,4-oxadiazoles. Facile synthesis and a broad substrate scope produce a range of compounds, some of them with potential as high-energy compounds. Heats of formation (ΔHf) and densities (ρ) were calculated, and heats of decomposition (ΔHd) and combustion (ΔHc) were determined experimentally. The densities of seven of the synthesized compounds were determined by gas pycnometry, and the respective values of detonation velocity (VD), detonation pressure (PD) and specific impulse (ISP) were calculated using the EXPLO5 program. An X-ray structure of 2-(2,4-dinitrophenyl)-5-(3,5-dinitrophenyl)-1,3,4-oxadiazole (4n) revealed the non-planarity of the molecule and afforded a crystal density of 1.698 (at 120 K), close to the pycnometric value of 1.64 at room temperature. Efficient cyclization between nitro-substituted benzohydrazides and nitro-substituted benzoic acids affords energetic 1,3,4-oxadiazoles.
- Wang, Zuoquan,Zhang, Hong,Killian, Benjamin J.,Jabeen, Farukh,Pillai, Girinath G.,Berman, Heather M.,Mathelier, Michael,Sibble, Ashani J.,Yeung, Justin,Zhou, Wenfeng,Steel, Peter J.,Hall, C. Dennis,Katritzky, Alan R.
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p. 5183 - 5188
(2015/08/18)
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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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- Synthesis and Properties of Energetic 1,2,4-Oxadiazoles
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The synthesis and characterization of a series of 3,5-di-aryl-1,2,4-oxadiazoles are reported and the effects of nitro groups in the aromatic rings on the experimental heats of decomposition (ΔHd) and heats of combustion (ΔHc) are evaluated. Heats of formation (ΔHf) and densities (ρ) were calculated and correlations between ΔHd and ΔHf were assessed for these compounds. Experimental determination of ρ (by gas pycnometry) on a selection of the compounds led to the calculation of detonation velocity (VD), detonation pressure (PD) and specific impulse (ISP) parameters by the Explo 5 program. An X-ray analysis of compound (4i) confirmed the structure and showed a crystal density (at 120 K) close to that determined by gas pycnometry.
- Wang, Zuoquan,Zhang, Hong,Jabeen, Farukh,Gopinathan-Pillai, Girinath,Arami, Justin A.,Killian, Benjamin J.,Stiegler, Kelcie D.,Yudewitz, Dalia S.,Thiemann, Pauline L.,Turk, Jessica D.,Zhou, Wenfeng,Steel, Peter J.,Hall, C. Dennis,Katritzky, Alan R.
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p. 7468 - 7474
(2016/01/25)
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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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- Macrocyclic peptoids by selective s-acylation of cysteine esters
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Optimized selective S-acylations of cysteine esters gave intermediates for the synthesis of macrocyclic peptoids by a benzotriazole-based method. Georg Thieme Verlag Stuttgart · New York.
- Ibrahim, Mohamed A.,Panda, Siva S.,Nhon, Linda,Hamed, Ahmed,El-Feky, Said A.,Katritzky, Alan R.
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p. 767 - 772
(2013/04/10)
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- Microwave-assisted regiospecific synthesis of pseudohalohydrin esters
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N-Acylbenzotriazoles react regiospecifically with epoxides under palladium catalysis to give novel -(benzotriazol-1-yl)ethyl esters (52-87%) constituting halohydrin ester surrogates. Georg Thieme Verlag Stuttgart · New York.
- El Khatib, Mirna,Elagawany, Mohamed,Todadze, Ekaterina,Khelashvili, Levan,El-Feky, Said A.,Katritzky, Alan R.
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supporting information; experimental part
p. 1384 - 1388
(2012/07/27)
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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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- Selective synthesis and structural elucidation of S-acyl- and N-acylcysteines
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(Chemical Equation Presented) N-(Acyl)-1H-benzotriazoles 6a-f react with L-cysteine 5 at 20°C to give exclusively (i) N-acyl-L-cysteines 8a-e in the presence of triethylamine in CH3CN-H2O (3:1), but (ii) S-acyl-L-cysteines 7a-e in CH
- Katritzky, Alan R.,Tala, Srinivasa R.,Abo-Dya, Nader E.,Gyanda, Kapil,El-Gendy, Bahaa El-Dien M.,Abdel-Samii, Zakaria K.,Steel, Peter J.
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body text
p. 7165 - 7167
(2009/12/09)
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- Cinnamoyl inhibitors of tissue transglutaminase
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(Figure Presented) Transglutaminases (TGases) catalyze the intermolecular cross-linking of certain proteins and tissue TGases (TG2) are involved in diverse biological processes. Unregulated, high TGase activities have been implicated in several physiological disorders, but few reversible inhibitors of TG2 have been reported. Herein, we report the synthesis of a series of novel trans-cinammoyl derivatives, discovered to be potent inhibitors of guinea pig liver transglutaminase. The most effective inhibitors evaluated can be sorted into two subclasses: substituted cinnamoyl benzotriazolyl amides and the 3-(substituted cinnamoyl)pyridines, referred to more commonly as azachalcones. Kinetic evaluation of both of these subclasses revealed that they display reversible inhibition and are competitive with acyl donor TGase substrates at IC50 values as low as 18 μM. An analysis of structure - activity relationships within these series of inhibitors permitted the identification of potentially important binding interactions. Further testing of some of the most potent inhibitors demonstrated their selectivity for TG2 and their potential for further development.
- Pardin, Christophe,Pelletier, Joelle N.,Lubell, William D.,Keillor, Jeffrey W.
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p. 5766 - 5775
(2008/12/22)
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- CINNAMOYL INHIBITORS OF TRANSGLUTAMINASE
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A compound of Formula, (I) or Formula: (II)
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Page/Page column 72
(2009/01/20)
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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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- Efficient microwave access to polysubstituted amidines from imidoylbenzotriazoles
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Microwave reactions of primary and secondary amines with imidoylbenzotriazoles 6a-w gave diversely substituted amidines 7a-Aa in 76-94% yields. Convenient preparations of a variety of amides 5a-Ab (87-96%) and imidoylbenzotriazoles 6a-w (56-95%) have also been developed using microwave irradiation under mild conditions and short reaction times. These results demonstrate further the advantages of microwave synthesis and introduce a new application of imidoylbenzotriazoles in the preparation of polysubstituted amidines.
- Katritzky, Alan R.,Cai, Chunming,Singh, Sandeep K.
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p. 3375 - 3380
(2007/10/03)
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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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- Regiospecific C-acylation of pyrroles and indoles using N-acylbenzotriazoles
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Reactions of pyrrole (2) or 1-methylpyrrole (4) with readily available N-acylbenzotriazoles 1a - g (RCOBt, where R = 4-tolyl, 4-nitrophenyl, 4-diethylaminophenyl, 2-furyl, 2-pyridyl, 2-indolyl, or 2-pyrrolyl) in the presence of TiCl4 produced 2
- Katritzky, Alan R.,Suzuki, Kazuyuki,Singh, Sandeep K.,He, Hai-Ying
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p. 5720 - 5723
(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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