Related Products of 16263-52-8, The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.16263-52-8, Name is 3-Chloro-1,2-benzisoxazole, molecular formula is C7H4ClNO. In a Article£¬once mentioned of 16263-52-8
Novel benzisoxazole derivatives as potent and selective inhibitors of acetylcholinesterase
A series of N-benzylpiperidine benzisoxazoles has been developed as potent and selective inhibitors of the enzyme acetylcholinesterase (AChE). The benzisoxazole heterocycle was found to be an appropriate bioisosteric replacement for the benzoyl functionality present in the N-benzylpiperidine class of inhibitors. The title compounds were synthesized by alkylating 3- methyl-1,2-benzisoxazoles with an iodo piperidine derivative as the key step. Benzisoxazoles 1b-j,o displayed potent inhibition of AChE in vitro with IC50’s = 0.8-14 nM. Particularly interesting were N-acetyl and morpholino derivatives 1g (IC50 = 3 nM) and 1j (IC50 = 0.8 nM), respectively, which displayed outstanding selectivity for acetyl- over butyrylcholinesterase, in excess of 3 orders of magnitude. N-acetyl 1g also displayed a favorable profile in vivo. This analog showed a dose-dependent elevation of total acetylcholine in mouse forebrain after oral administration with an ED50 = 2.4 mg/kg. In addition, 1g was able to reverse amnesia in a mouse passive avoidance model at doses of 3.2 and 5.6 mg/kg with an average reversal of 89.7%. Molecular dynamics simulations were used to study the possible binding modes of N-benzylpiperidine benzisoxazoles to AChE from Torpedo californica. Key structural insights were obtained regarding the potency of this class of inhibitors. Specifically, Asp-72, Trp-84, Trp-279, Phe-288, and Phe-330 are implicated in the binding of these inhibitors. The N-benzylpiperidine benzisoxazoles may be suitable compounds for the palliative treatment of Alzheimer’s Disease.
We¡¯ll also look at important developments in the pharmaceutical industry because understanding organic chemistry is important in understanding health, medicine, the role of 16263-52-8, and how the biochemistry of the body works.Related Products of 16263-52-8
Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics