- Multi-Targeting Tacrine Conjugates with Cholinesterase and Amyloid-Beta Inhibitory Activities: New Anti-Alzheimer's Agents
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Alzheimer's disease (AD) is a severe age dependent and chronic problem with no cure so far. The available treatments are temporary, acting over short period of time. The main pathological hallmark of the disease includes cholinergic dysfunction, oxidative stress, accumulation of Aβ fibrils and tau tangles. In context with the multi-factorial nature of this disease, two different series of molecules were developed to hit the multifactorial disease targets. Mainly, the molecules were designed to inhibit the AChE and aggregation of Aβ, and also oxidative damage. Two novel series of TAC-fenbufen/menbutone conjugated molecules were designed, synthesized and bio-assayed. All compounds showed inhibition capacity towards AChE, Aβ aggregation and moderate to good radical scavenging capacity. Particularly, five TAC-menbutone molecules showed improved AChE and Aβ aggregation inhibition capacity compared to TAC-fenbufen conjugated molecules. Overall, these novel series of molecules may be potential drug lead molecules in the treatment of AD.
- Hiremathad, Asha,Chaves, Sílvia,Keri, Rangappa S.
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- Improved meng Butong method for the synthesis of
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The invention discloses an improved synthesis method of menbutone. The method specifically comprises the following steps: dissolving 1-methoxy naphthalene and succinic anhydride in dichloromethane, cooling to 1-3 DEG C under stirring, slowly adding aluminum trichloride, heating solution to 35+/-2 DEG C, reacting in thermal insulation for 5.5-6.5 hours, pouring the reaction solution in an ice water mixture after the thermal insulation reaction, stirring, standing, crystallizing and suction-filtering, wherein the filter cake is a menbutone crude product; heating and distilling the filtrate to recycle dichloromethane; and then recrystallizing the menbutone crude product by using water as a solvent, and decoloring through activated carbon to obtain a menbutone competitive product. The synthesis method disclosed by the invention is simple, dichloromethane, which is the class 2 solvent with small use toxicity and high security degree, is used, the damage on the operator and environment is small, the solvent can be recycled, and the fished product yield is high to 86.4%; the synthesis method can be used for industrially synthesizing menbutone, and has good environment benefit and economic benefit.
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Paragraph 0016-0018
(2017/04/14)
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