6202-74-0Relevant articles and documents
Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors
Alamir, Amir,Asgari, Mohammad Sadegh,Bandarian, Fatemeh,Faramarzi, Mohammad Ali,Hajimiri, Mir Hamed,Hamedifar, Haleh,Hosseini, Samanesadat,Iraji, Aida,Larijani, Bagher,Mahdavi, Mohammad,Mojtabavi, Somayeh,Moradi, Shahram,Nasli Esfahani, Anita,Nasli-Esfahani, Ensieh
, (2021/09/18)
A novel series of phenoxymethybenzoimidazole derivatives (9a-n) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC50 values in the range of 6.31 to 49.89?μM compared to standard drug acarbose (IC50 = 750.0 ± 10.0?μM). Enzyme kinetic studies on 9c, 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor.
Synthesis, in vitro assays, molecular docking, theoretical ADMET prediction, and evaluation of 4-methoxy-phenylthiazole-2-amine derivatives as acetylcholinesterase inhibitors
Zhang, Xiao-Zhong,Xu, Yuan,Jian, Meng-Meng,Yang, Kan,Ma, Zheng-Yue
, p. 1683 - 1693 (2019/08/02)
Based on the cholinergic hypothesis of the reported compound, N-(4-(4-methoxy-phenyl)thiazol-2-yl)-3-(pyrrolidin-1-yl)propionamide, which had a good inhibitory activity to acetylcholinesterase (AChE), the new 4-methoxy-phenylthiazole-2-amine derivatives as AChE inhibitors (AChEIs) have been designed and synthesized in this study. Their chemical structures were confirmed by proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, mass spectrometry, and infrared. Furthermore, their inhibitory activities against AChE in vitro were also tested by Ellman spectrophotometry, and the inhibitory activity test results showed that most of the compounds of 4-methoxy-phenylthiazole-2-amine derivatives had a certain AChE inhibitory activity in vitro, and the IC50 (half-maximal inhibitory concentration) value of compound 5g was 5.84 μmol/L, which was higher than that of the reference compound, rivastigmine. Moreover, it had almost no inhibitory effect on butyrylcholinesterase. In addition, compound 5g was subjected to enzyme inhibition kinetics experiments, and the result of Lineweaver–Burk’s V?1–[S]?1 double-reciprocal plot showed that the acting type of compound 5g was mixed inhibition type. Furthermore, the AChE inhibitory activity mechanism of compound 5g was explored by the conformational analysis and molecular docking, which was based on the principle of the four-point pharmacophore model necessary for AChE inhibition. Finally, in silico molecular property and ADMET (absorption, distribution, metabolism, excretion, and toxicity) of the synthesized compounds were predicted by using Molinspiration and PreADMET online servers, respectively. It can be concluded that the lead AChEI compound 5g presented satisfactory drug-like characteristics and ADME properties.
Design, synthesis and molecular docking of pyrazolo [3,4d] thiazole hybrids as potential anti-HIV-1 NNRT inhibitors
Kasralikar,Jadhavar,Goswami,Kaminwar,Bhusare
, p. 437 - 444 (2019/02/17)
A series of pyrazolo[3.4,d]thiazole hybrids 6 were synthesized from 5-arylidene-2-imino-3-(4-arylthiazol-2-yl)-thiazolidin-4-ones 5. The 5-arylidene-2-imino-3-(4-arylthiazol-2-yl)-thiazolidin-4-ones 5 were synthesized from 2-amino-4-arylthiazoles 1 and 2-chloro-acetamido-4-arylthiazoles 2 via the formation of 2-imino-3-(4-substituted-arylthiazol-2-yl)-thiazolidin-4-ones 3 using substituted aldehydes 4. The 5-acrylidene derivative 5 on cyclisation with phenyl hydrazine give the pyrazolo [3, 4, d] thiazole derivatives 6. The obtained pyrazolo [3.4, d]thiazole derivatives were studied as anti-HIV-1 NNRT inhibitors. It was found that these compounds might have potent RT inhibition activity.
Synthesis, biological evaluation, and docking studies of novel 5,6-diaryl-1,2,4-triazine thiazole derivatives as a new class of α-glucosidase inhibitors
Wang, Guangcheng,Peng, Zhiyun,Gong, Zipeng,Li, Yongjun
, p. 195 - 200 (2018/04/02)
A novel 5,6-diaryl-1,2,4-triazine thiazole derivatives (7a-7q) were synthesized and characterized by 1H NMR and 13C NMR and evaluated for their α-glucosidase inhibitory activity. All tested compounds displayed good α-glucosidase inhibitory activity with IC50 values ranging between 2.85 ± 0.13 and 14.19 ± 0.23 μM when compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μM). Compound 7i (IC50 = 2.85 ± 0.13 μM) exhibited the highest activity among this series of compounds. Molecular docking studies were carried out in order to investigate the binding mode of this class of compounds to α-glucosidase. This study showed that these 5,6-diaryl-1,2,4-triazine thiazole derivatives are a new class of α-glucosidase inhibitors.
Β - secretase enzyme has the function of inhibiting compound, the preparation of the compounds and use thereof
-
, (2018/03/26)
The invention discloses a compound capable of inhibiting beta-secretase, and a preparation method and application thereof. The structure of the compound is shown in a formula I, formula II or formula III as described in the specification. In the formula I, X is S or NH; R1 is selected from hydrogen and nitro group; R2 and R4 are same or different and independently selected from the group consisting of hydrogen, halogen, nitro group and substituted aryl group; R3 is selected from the group consisting of hydrogen, nitro group, straight-chain and branched-chain alkyl and substituted alkyl groups with a carbon number of 1 to 4, alkylamino or alkyloxy group with a carbon number of 1 to 4 and alkylamido group with a carbon number of 1 to 4; R is located at position 2, 3 or 4 of a benzene ring and selected from the group consisting of hydrogen, straight-chain and branched-chain alkyl and substituted alkyl groups with a carbon number of 1 to 4, alkylamino or alkyloxy group with a carbon number of 1 to 4 and alkylamido group with a carbon number of 1 to 4. In the formula II, R is selected from different substituted aryl groups. In the formula III, R is selected from hydrogen or cyano group. Experiments prove that the compound provided by the invention has good beta-secretase inhibitory activity and has wide application values as a beta-secretase inhibitor.
2-Substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamides as BACE1 inhibitors: Synthesis, biological evaluation and?docking studies
Yan, Gang,Hao, Lina,Niu, Yan,Huang, Wenjie,Wang, Wei,Xu, Fengrong,Liang, Lei,Wang, Chao,Jin, Hongwei,Xu, Ping
, p. 462 - 475 (2017/06/19)
In this work, a series of 2-substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamide derivatives were developed as β-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. In addition, the selected compounds were tested with affinity (KD) towards BACE-1, blood brain barrier (BBB) permeability and cytotoxicity. The studies revealed that the most potent analog 41 (IC50 = 4.6 μM) with high predicted BBB permeability and low cellular cytotoxicity, could serve as a good lead structure for further optimization.
Design and discovery of novel thiazole derivatives as potential MMP inhibitors to protect against acute lung injury in sepsis rats: Via attenuation of inflammation and apoptotic oxidative stress
Ge, Lingqing,Hu, Qiaozhen,Shi, Mengrao,Yang, Huiyun,Zhu, Guoji
, p. 32909 - 32922 (2017/07/10)
Acute lung injury (ALI) is considered to be an inflammatory syndrome of the airway system that is initiated by failure of the respiratory system. In this study, we evaluated the possible benefits of some novel thiazole derivatives against ALI. These derivatives were synthesised and evaluated for the inhibition of MMP-8 and MMP-2. Most of the tested compounds had better inhibitory activity for MMP-8 than for MMP-2, with compound 26 being the most potent analogue among the tested series. Thus, compound 26 was further investigated to determine its beneficial effects in an ALI model of rats with sepsis. In vivo results suggested that compound 26 significantly reduced the protein concentration together with a decline in enhanced leukocytes compared with those in ALI induced by cecal ligation and puncture. The effect of compound 26 on myeloperoxidase activity was also quantified, which was found to be significantly reduced at the maximum tested dose of 20 mg kg-1. The protective effect of compound 26 against ALI was also established to occur via the significant modulation of various biomarkers; for example, the malondialdehyde level was found to be reduced, while there were increased levels of superoxide dismutase and glutathione. Thus, it is proposed that compound 26 exerts a protective effect against ALI via modulation of the antioxidant status. Furthermore, the compounds tested caused significant attenuation of the levels of tumour necrosis factor-α, interleukin-1β, and interleukin-6, and protected the lung through the modulation of systemic inflammatory mediators in septic rats. In conclusion, we identified a novel series of thiazoles, which potentially exert protective effects against ALI via the inhibition of numerous pathways.
Synthesis, antibacterial, antifungal, and antioxidant evaluation of some new thiazole clubbed oxadiazole derivatives
Monga, Vikramdeep,Singh, Hargyan,Singh, Gurpreet
, p. 51 - 57 (2019/01/16)
A series of thiazole incorporated oxadiazole derivatives (6a-6f) was synthesized by reacting 2-chloro-N-(4-(4-substituted phenyl) thiazol-2-yl) acetamide with 5-pyridine-1,3,4-oxadiazole-2-thione using multistep solution phase chemistry. The synthesized compounds were structurally characterized on the basis of elemental analysis and using various spectral data. All the compounds were evaluated for their in vitro antibacterial, antifungal, and antioxidant activity. Some of the new compounds exhibited good antimicrobial and antioxidant activity and are suitable candidates for further scientific explorations.
Synthesis and free radical scavenging activity of 2-alkyl/arylchalcogenyl-N-(4-aryl-1,3-thiazol-2-yl)acetamide compounds
Wolf, Lucas,Quoos, Natália,Mayer, Jo?o C.P.,De Souza, Diego,Sauer, André C.,Meichtry, Luana,Bortolotto, Vandreza,Prigol, Marina,Rodrigues, Oscar E.D.,Dornelles, Luciano
, p. 1031 - 1034 (2016/02/16)
The synthesis of a new series of organochalcogen-derivatives, 2-alkyl/arylchalcogenyl-N-(4-aryl-1,3-thiazol-2-yl)acetamides 5a-r, provided products in satisfactory yields, which varied from 42% to 95%. All these novel compounds were screened for their in vitro free radical scavenging activity against 2,2-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. Compounds 5 (m, h, i, f, q, g, l, c, n) were effective scavengers against the ABTS radical species but less effective on scavenging the DPPH radical, indicating that the antioxidant effect of these compounds were related to protonated radical scavenger activity.
Design and Synthesis of 3-Substituted-thiazolyl-2-iminothiazolidin-4-ones as a New Class of Anticonvulsants
Alagarsamy,Senthilraja,Raja Solomon
, p. 1635 - 1639 (2016/09/23)
A new series of 3-substituted-thiazolyl-2-iminothiazolidin-4-ones were synthesized by nucleophilic substitution of p-substituted-thiazol-2-yl-chloroacetamides with potassium thiocyanide by cyclization. The starting material p-substituted-thiazol-2-yl-chloroacetamides were synthesized from p-substituted-thiazol-2-yl-amines with chloroacetyl chloride, which in turn was prepared from one pot reaction of substituted aryl acetophenone and amino group of thiourea. The title compounds were investigated for their anticonvulsant activity. Among the tested compounds, compound 3-(4-(4-fluorophenyl)thiazol-2-yl)-2-iminothiazolidin-4-one (16) emerged as the most active compound of the series, and it is moderately more potent than the reference standard diazepam.
