63823-75-6Relevant articles and documents
Benzoheterocyclic Oxime Carbamates Active against Mycobacterium tuberculosis: Synthesis, Structure-Activity Relationship, Metabolism, and Biology Triaging
Van Der Westhuyzen, Renier,Mabhula, Amanda,Njaria, Paul M.,Müller, Rudolf,Ngumbu Muhunga, Denis,Taylor, Dale,Lawrence, Nina,Njoroge, Mathew,Brunschwig, Christel,Moosa, Atica,Singh, Vinayak,Rao, Srinivasa P.S.,Manjunatha, Ujjini H.,Smith, Paul W.,Warner, Digby F.,Street, Leslie J.,Chibale, Kelly
supporting information, p. 9444 - 9457 (2021/07/19)
Screening of a library of small polar molecules against Mycobacterium tuberculosis (Mtb) led to the identification of a potent benzoheterocyclic oxime carbamate hit series. This series was subjected to medicinal chemistry progression underpinned by structure-activity relationship studies toward identifying a compound for proof-of-concept studies and defining a lead optimization strategy. Carbamate and free oxime frontrunner compounds with good stability in liver microsomes and no hERG channel inhibition liability were identified and evaluated in vivo for pharmacokinetic properties. Mtb-mediated permeation and metabolism studies revealed that the carbamates were acting as prodrugs. Toward mechanism of action elucidation, selected compounds were tested in biology triage assays to assess their activity against known promiscuous targets. Taken together, these data suggest a novel yet unknown mode of action for these antitubercular hits.
Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection
Li, Qi,Chen, Ying,Xing, Shuaishuai,Liao, Qinghong,Xiong, Baichen,Wang, Yuanyuan,Lu, Weixuan,He, Siyu,Feng, Feng,Liu, Wenyuan,Chen, Yao,Sun, Haopeng
, p. 6856 - 6876 (2021/05/29)
Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close association with Aβ deposit. Here, we identified S06-1011 (hBChE IC50 = 16 nM) and S06-1031 (hBChE IC50 = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in scopolamine- and Aβ1-42 peptide-induced cognitive deficit models. The best candidate S06-1011 increased the level of ghrelin, a substrate of BChE, which can function as improving the mental mood appetite. The weight gain of the S06-1011-treated group remarkably increased. Hence, BChE inhibition not only plays a protective role against dementia but also exerts a great effect on treating and nursing care.
Butyrylcholine esterase selective inhibitor and preparation method and application thereof
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Paragraph 0032; 0033; 0034, (2019/02/19)
The invention discloses a butyrylcholine esterase selective inhibitor and a preparation method and application thereof. The invention discloses a compound shown in a formula (I), and also discloses application of the compound in preparation of medicines for preventing or treating Alzheimer's disease. An inventor uses the inhibiting activity of butyrylcholine esterase, selective screening and Morris water maze experiment as carriers to evaluate the function of the compound in the formula (I) for treating the Alzheimer's disease (especially medium and severe Alzheimer's disease), the good in-vitro and in-vivo activities and higher selectivity are found, and the compound can be further developed into a precursor substance which can selectively inhibit the butyrylcholine esterase to reach thefunction of treating the Alzheimer's disease. The formula (I) is shown in the specification.
