588-07-8Relevant articles and documents
One-Pot Regioselective and Stereoselective Synthesis of C-Glycosyl Amides from Glycals Using Vinyl Azides as Glycosyl Acceptors
Rasool, Faheem,Ahmed, Ajaz,Hussain, Nazar,Yousuf, Syed Khalid,Mukherjee, Debaraj
, p. 4036 - 4039 (2018)
The reaction of glycals containing good leaving groups with aromatic vinyl azides to give α-C-glycosyl amides in good yields is described. Various vinyl azides with different groups undergo the reaction smoothly. In these reactions, an iminodiazonium intermediate is generated by the attack of the vinyl azide onto the glycal under Lewis acid conditions. This undergoes Schmidt-type denitrogenative 1,2-migration to form a nitrilium ion, which, upon hydrolysis, gives the desired C-glycosyl amide.
Direct para-Selective C-H Amination of Iodobenzenes: Highly Efficient Approach for the Synthesis of Diarylamines
Chen, Yujie,Huang, Zhibin,Jiang, Yaqiqi,Shu, Sai,Yang, Shan,Shi, Da-Qing,Zhao, Yingsheng
, p. 8226 - 8235 (2021/06/28)
Iodine(III)-mediated synthesis of 4-iodo-N-phenylaniline from iodobenzene has been achieved, and the reaction can proceed under mild conditions. A variety of functional groups were well tolerated, providing the corresponding products in moderate to good yields. The remaining iodine group provides an effective platform for converting the products into several valuable asymmetric diphenylamines. Most importantly, this reaction can be easily scaled up to the ten-gram scale, highlighting its synthetic utility. The mechanistic study revealed that the in situ generated aryl hypervalent iodine intermediate is the key factor to realize this para-selective C-H amination reaction.
Hybrid quinoline-thiosemicarbazone therapeutics as a new treatment opportunity for Alzheimer’s disease-synthesis, in vitro cholinesterase inhibitory potential and computational modeling analysis
Alsaab, Hashem O.,Aqsa, Sehar,Asif, Tahira Tasneem,Ibrar, Aliya,Kausar, Naghmana,Khan, Imtiaz,Munir, Rubina,Shahid, Noorma,Younas, Muhammad Tayyab,Zaib, Sumera
, (2021/12/10)
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. The limited pharmacological approaches based on cholinesterase inhibitors only provide symptomatic relief to AD patients. Moreover, the adverse side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with these drugs and numerous clinical trial failures present substantial limitations on the use of medications and call for a detailed insight of disease heterogeneity and development of preventive and multifactorial therapeutic strategies on urgent basis. In this context, we herein report a series of quinoline-thiosemicarbazone hybrid therapeutics as selective and potent inhibitors of cholinesterases. A facile multistep synthetic approach was utilized to generate target structures bearing multiple sites for chemical modifications and establishing drug-receptor interactions. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). In vitro inhibitory results revealed compound 5b as a promising and lead inhibitor with an IC50 value of 0.12 ± 0.02 μM, a 5-fold higher potency than standard drug (galantamine; IC50 = 0.62 ± 0.01 μM). The synergistic effect of electron-rich (methoxy) group and ethylmorpholine moiety in quinolinethiosemicarbazone conjugates contributes significantly in improving the inhibition level. Molecular docking analysis revealed various vital interactions of potent compounds with amino acid residues and reinforced the in vitro results. Kinetics experiments revealed the competitive mode of inhibition while ADME properties favored the translation of identified inhibitors into safe and promising drug candidates for pre-clinical testing. Collectively, inhibitory activity data and results from key physicochemical properties merit further research to ensure the design and development of safe and high-quality drug candidates for Alzheimer’s disease.
