Reactions and Biological Activities of Hydrazonoyl Halides.

This review covers the literature information on the chemistry of hydrazonoyl halides with different substrates to give heterocyclic compounds. From the foregoing survey, it seems this provides a useful and convenient strategy for the synthesis of numerous heterocyclic derivatives. The subject of such reactions is still ongoing and undoubtedly will provide new fused functionalized compounds of both industrial and biological interest. A literature survey revealed that a great deal of interest has been focused on the synthesis of functionalized heterocyclic compounds due to their wide range of biological activities, such as contact dermatitis, anthelmintic, antiviral, antimicrobial, herbicidal, and anti-cancer. On the other hand, hydrazonoyl halides are interesting synthons for valuable bioactive heterocyclic compounds. The reaction of hydrazonoyl halides with various types of substrates gave a huge number of different heterocyclic systems. In this review, we collected all reactions of hydrazonoyl halides with different moieties and classified them as aryl diazo of monoheterocycles, aryldiazo of 5,5-bis-heterocycles, aryldiazo of 5,6-bis-heterocycles, aryldiazo of 6,6-bis-heterocycles, aryldiazo of 5,5,6-tri-heterocycles, aryldiazo of 5,6,6-tri-heterocycles, aryldiazo of 6,6,6-tri-heterocycles, hetero annulation of bisheterocycles, hetero annulation of tri-heterocycles, hetero-annulation of tetra-heterocycles, synthesis of spiro-heterocycles, heterocyclic ring transformations, and 1,3-dipolar cycloaddition reactions catalyzed by transition metals using hydrazonoyl halides as substrates.Most reaction types have been successfully applied and used in the production of biologically active compounds. The aim of the present survey is to consider in the reader the opportunity interactions and biological activities of hydrazonoyl halides. The information of several artificial paths and varied physics-chemical factors of such heterocycles made a special consideration of chemists in different fields to yield a combinatorial library and carry out thorough efforts in the search for hydrazonoyl halides.

Design, synthesis, and biological evaluation of 1,2,4-oxadiazole-based derivatives as multitarget anti-Alzheimer agents.

A series of novel 1,2,4-oxadiazole-based derivatives were synthesized and evaluated for their potential anti-Alzheimer disease activity. The results revealed that compounds 2b, 2c, 2d, 3a, 4a, 6, 9a, 9b, and 13b showed excellent inhibitory activity against acetylcholinesterase (AChE) with IC50 values in the range of 0.0158 to 0.121 µM. They were 1.01 to 7.78 times more potent than donepezil (IC50 = 0.123 µM). The newly synthesized compounds exhibited lower activity towards butyrylcholinesterase (BuChE) when compared to rivastigmine. Compounds 4b and 13b showed the most prominent inhibitory potential against BuChE with IC50 values of 11.50 and 15 µM, respectively. Moreover, 4b, and 9b were found to be more potent antioxidant agents (IC50 values of 59.25, and 56.69 µM, respectively) in comparison with ascorbic acid (IC50 = 74.55 µM). Compounds 2b and 2c exhibited monoamine oxidase-B (MAO-B) inhibitory activity with IC50 values of 74.68 and 225.48 µM, respectively. They were 3.55 and 1.17 times more potent than biperiden (IC50 = 265.85 µM). The prominent interactions of the compounds with the AChE active site can be used to computationally explain the high AChE inhibitory activity. The results unveiled 1,2,4-oxadiazole derivatives 2c and 3a as multitarget anti-AD agents. The predicted ADME properties for compounds 2b and 4a were satisfactory, and 4a had the highest likelihood of crossing the blood-brain barrier (BBB), making it the optimum compound for future optimization.