- 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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- Synthesis and QSAR studies of novel triazole compounds containing thioamide as potential antifungal agents
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Eighteen novel triazole compounds containing thioamide were designed and synthesized. Their structures were confirmed by elemental analysis, 1H NMR, IR, and MS. The title compounds exhibited certain antifungal activity. And the geometry structures of the title compounds were optimized by means of the density functional theory (DFT) method at B3LYP/6-31G* level. The quantitative structure-activity relationship (QSAR) of the title compounds was systematically investigated. A correlative equation between FA and DELH, V was well established by using the multiple linear regression (MLR).
- Wei, Qing-Li,Zhang, Shu-Sheng,Gao, Jun,Li, Wei-hua,Xu, Liang-Zhong,Yu, Zhi-Gang
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p. 7146 - 7153
(2007/10/03)
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- One-carbon homologation of carboxylic acids via BtCH2TMS: A safe alternative to the Arndt-Eistert reaction
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Carboxylic acids are converted into the corresponding homologated acids or esters, using easily available 1-(trimethylsilylmethyl)benzotriazole (1) as a one-carbon synthon. The effectiveness of the reaction has been investigated on six aryl and seven alkyl carboxylic acids.
- Katritzky,Zhang,Haleem,Hussein,Fang,Steel
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p. 5606 - 5612
(2007/10/03)
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- BtCH2TMS-assisted Homologation of Carboxylic Acids: A Safe Alternative to the Arndt-Eistert Reaction
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formula presented One-carbon homologation of carboxylic acids is achieved by (i) treatment of an acyl chloride with 1-[(trimethylsilyl)methyl]-1H-1,2,3,-benzotriazole (BtCH2TMS) (1) to afford N-(acylmethyl)benzotriazoles 3a-f, followed by (ii) conversion of 3a-f with triflic anhydride into RC(OTf)=CHBt 4a-f, and (iii) the subsequent reaction of 4a-c with NaOCH3 followed by 1N HCl to afford esters RCH2CO2R′ 7a-c in overall yields of 50-70%. For the aliphatic compounds 5d-f, treatment of 5d-f with p-toluenesulfonic acid followed by TBAF/THF afforded acids RCH2COOH 7d-f.
- Katritzky, Alan R.,Zhang, Suoming,Fang, Yunfeng
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p. 3789 - 3791
(2007/10/03)
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- Flash vacuum pyrolysis of stabilised phosphorus ylides. Part 11. Unexpected generation and rearrangement of acetyl benzotriazolyl carbene
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Seventeen novel α-benzotriazolyl-β-oxo phosphorus ylides 2 have been prepared and characterised. Flash vacuum pyrolysis (FVP) of these generally leads to loss of both R13PO and N2 to give intractable products but, in one case, 21, extrusion of Bu3P is observed to give 3-acetyl-1,2,4-benzotriazine 6 and 2′-cyanoaceto-phenone 7, products apparently derived from rearrangement of the initially formed carbene 11, and involving in the latter case a novel 1,3-acetyl migration process.
- Aitken, R. Alan,Fairhurst, Ian M.,Ford, Adrian,Milne, Paul E. Y.,Russell, Duncan W.,Whittaker, Martin
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p. 3107 - 3112
(2007/10/03)
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- A Novel Transformation of Esters to Alkynes with 1-Substituted Benzotriazoles
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Reactions of lithio benzotriazol-1-yl derivatives 2, 11, and 25 with aromatic and aliphatic esters 3, 12, and 26 gave α-(benzotriazol-l-yl) ketones 4, 13, and 27, respectively, in high yields. Alternatively, α-(benzotriazol-l-yl) ketones 22 can be accessed by the reaction of α-(benzotriazol-1-yl) esters 20 with Grignard reagents. Condensation of 4, 13, 22, and 27 with (p-toluenesulfonyl)hydrazine provided p-tosylhydrazones 5, 14, 21, and 28. Treatment of hydrazones 5, 21, and 28 with n-butyllithium in diethyl ether resulted in the elimination of the tosyl group, dinitrogen, and benzotriazolyl group to afford the corresponding acetylenes 9, 23, and 29 in good yields. When α-(benzotriazol-l-yl) 1-α-phenoxy hydrazones 14 were treated with methyllithium, n-butyllithium, or phenyllithium, alkynes 18 were obtained, in which phenoxy groups were replaced by the lithium reagents.
- Katritzky, Alan R.,Wang, Jin,Karodia, Nazira,Li, Jianqing
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p. 4142 - 4147
(2007/10/03)
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