Design, synthesis and biological evaluation of potential anti-AD hybrids with monoamine oxidase B inhibitory and iron-chelating effects was written by Guo, Jianan;Mi, Zhisheng;Jiang, Xiaoying;Zhang, Changjun;Guo, Zili;Li, Linzi;Gu, Jinping;Zhou, Tao;Bai, Renren;Xie, Yuanyuan. And the article was included in Bioorganic Chemistry in 2021.Synthetic Route of C6H9ClO3 The following contents are mentioned in the article:
A series of active hybrids combining 3-hydroxypyridin-4(1H)-one and coumarin pharmacophores were designed and synthesized as potential agents for the treatment of Alzheimer’s disease (AD). All the compounds exhibited excellent iron-chelating activities (pFe3+ = 14.8-19.2) and showed favorable monoamine oxidase B (MAO-B) inhibitory effects compared to the reference drug Pargyline (IC50 = 86.9 nM). Among them, compound 11 g displayed the best MAO-B inhibitory activity with an IC50 value of 99.3 nM. Mol. docking anal. showed that compound 11 g could enter the entrance cavity and substrate cavity of MAO-B. Furthermore, the compound 11 g had an excellent antioxidant effect and was capable of protecting from the amyloid-β1-42 (Aβ1-42) induced PC12 cell damage. In silico tools were applied for predicting the blood-brain barrier (BBB) penetration and compound 11 g was proved to overcome the brain exposure challenge. In the mice behavioral study, compound 11 g significantly ameliorated cognitive impairment induced by Scopolamine. More importantly, compound 11 g displayed favorable pharmacokinetic profiles in a rat model. In summary, compound 11 g, with both anti-MAO-B and iron-chelating ability, was proved to be a promising potential anti-AD agent for further optimization. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Synthetic Route of C6H9ClO3).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators. Alkanes and aryl alkanes may be chlorinated under free radical conditions, with UV light. However, the extent of chlorination is difficult to control.Synthetic Route of C6H9ClO3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics