76700-83-9Relevant articles and documents
Synthesis, biological evaluation and docking study of a new series of di-substituted benzoxazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents
Kaur, Avneet,Pathak, Dharam P.,Sharma, Vidushi,Wakode, Sharad
, p. 891 - 902 (2018/01/22)
A new series of substituted-N-(3,4-dimethoxyphenyl)-benzoxazole derivatives 13a–13p was synthesized and evaluated in vitro for their COX (I and II) inhibitory activity, in vivo anti-inflammatory and ulcerogenic potential. Compounds 13d, 13h, 13k, 13l and 13n exhibited significant COX-2 inhibitory activity and selectivity towards COX-2 over COX-1. These selected compounds were screened for their in vivo anti-inflammatory activity by carrageenan induced rat paw edema method. Among these compounds, 13d was the most promising analogs of the series with percent inhibition of 84.09 and IC50 value of 0.04 μM and 1.02 μM (COX-2 and COX-1) respectively. Furthermore, ulcerogenic study was performed and tested compounds (13d, 13h, 13k, 13l) demonstrated a significant gastric tolerance than ibuprofen. Molecular docking study was also performed with resolved crystal structure of COX-2 to understand the binding mechanisms of newly synthesized inhibitors in the active site of COX-2 enzyme and the results were found to be concordant with the biological evaluation studies of the compounds. These newly synthesized inhibitors also showed acceptable pharmacokinetic profile in the in silico ADME/T analyses.
Synthesis, cyclooxygenase-2 inhibition, anti-inflammatory evaluation and docking study of substituted-n-(3,4,5-trimethoxyphenyl)-benzo[d]oxazole derivatives
Kaur, Avneet,Wakode, Sharad,Pathak, Dharam P.,Sharma, Vidushi,Shakya, Ashok K.
, p. 660 - 673 (2018/11/06)
Background: Non-steroidal anti-inflammatory drugs are widely used for many years, but the chronic use of NSAID’s leads to gastric side effects, ulceration and kidney problems. These side effects are due to non-selective inhibition of COX-2 along with COX-1. Therefore, it is imperative to develop novel and selective COX-2 inhibitors. Objective: In this paper wehave synthesized a series of novel hybrids comprising of substituted-N-(3,4,5-trimethoxyphenyl)-benzo[d]oxazole derivatives and screened for the treatment of inflammation. Methods: The structures of the obtained compounds were elucidated by elemental and spectral analysis (ATR-FTIR,1 H NMR,13 C NMR, Mass spectroscopy). All of the compounds were evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activity by in vitro enzymatic assay. The compound which showed COX-2 activity (3a-3e, 3g – 3h, 3k, 3m and 3o) was further screened for in vivo anti-inflammatory activity and ulcerogenic liability. Molecular docking study was also performed with resolved crystal structure of COX-2 to understand the binding mechanism of newly synthesized inhibitors in the active site of COX-2enzyme. Results: The in vitro COX-1 and COX-2 inhibitory studies showed that the synthesized compounds potentially inhibited COX-2 (IC50 = 0.04 – 26.41 μM range) over COX-1 (IC50 = 0.98 – 33.33 μM range). The in vivo studies predicted that compounds 3c (70.9%, 0.6±0.22), 3m (68.1%, 1.9±0.41) and 3o (70.4%, 1.7±0.27) produced more efficacy against carrageenan induced paw edema and less ulcerogenic effect, as compared to standard ibuprofen (65.9%, 2.2±0.44). The results of docking studies were found to be concordant with the biological evaluation studies of the prepared compound. Conclusion: Among all the tested compounds, 2-Chloro-N-(2-(3,4,5-trimethoxyphenyl)-benzo[d]oxazol-5-yl)-benzamide (3c) was the most potent anti-inflammatory agent and has less ulcerogenic potential. This series of compound can be explored more for development of safer and more active anti-inflammatory agents.
Construction of hetero[n]rotaxanes by use of polyfunctional rotaxane frameworks
Li, Ziyong,Liu, Guoxing,Xue, Wen,Wu, Di,Yang, Ying-Wei,Wu, Jishan,Liu, Sheng Hua,Yoon, Juyoung,Yin, Jun
, p. 11560 - 11570 (2013/12/04)
Heterorotaxanes, one class of topological organic structures, have attracted increasing interesting during the past two decades. In general, two types of heterorotaxane structures exist, one in which two or more different macrocycles are threaded onto one dumbbell-shaped molecule and the other where one macrocycle is threaded onto two or more different dumbbell-shaped molecules. In comparison to these traditional types, another family of topologically interesting heterorotaxanes can be envisaged as arising from polyfunctional molecules that possess both host (crown ether) and guest (ammonium templates). In the present investigation, we have explored the construction of selected members of this new heterorotaxane family, which possess crown ether moieties that are wrapped around a dumbbell-shaped molecule. These structures are prepared by routes in which "stitching" processes, involving template-directed clipping reaction or olefin metathesis reactions, are used to install crown ether ring systems encircling ammonium cation centers. This is then followed by implementation of a threading-followed-by-stoppering sequence to install a second encircling crown ether ring. The results show that the polyfunctional building blocks assemble with high efficiencies. Finally, this investigation provides a foundation for future studies aimed at constructing more complicated heterorotaxane architectures, such as switchable systems, self-assembling polymers, and functional molecular machines.
