66742-57-2Relevant articles and documents
A Two Hour Synthesis of the Anti-Parkinson Drug Safinamide Methanesulfonate
Higa, Vanessa M.,Omori, Alvaro T.
supporting information, p. 1433 - 1436 (2021/07/20)
The critical moment of the COVID-19 outbreak requires a real-time supply of therapeutic agents. Thus, time economy in the synthesis of biologically active compounds has become increasingly decisive. In this work, we developed a two hour synthesis of the a
Preparation method of safinamide mesylate intermediate
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Paragraph 0032-0050, (2020/12/15)
The invention relates to a preparation method of a safinamide mesylate intermediate, which comprises the following steps: under the protection of nitrogen, adding a concentrated organic phase into anorganic solvent, heating to 40-45 DEG C, cooling to 28-35 DEG C in a constant-speed cooling mode, and adding a mixture of seed crystal and the organic solvent; and cooling the solution system to 3-8 DEG C in a gradient cooling manner, filtering, and drying to obtain the target product safinamide mesylate intermediate, namely a compound 4-(3-fluorobenzyloxy) benzaldehyde shown in a formula 4. The organic phase obtained after the reflux reaction is purified and crystallized in a gradient cooling manner, and the product is directly obtained through one-step purification, so that the operation steps are simple, the efficiency and purity are greatly improved, the solvent consumption is reduced, the reaction conditions are mild and environment-friendly, and the safety and reliability of the preparation are improved. a safe and controllable medication principle is more favorably embodied, and the method has a relatively high industrial development prospect.
Evolution of a 4-Benzyloxy-benzylamino Chemotype to Provide Efficacious, Potent, and Isoform Selective PPARα Agonists as Leads for Retinal Disorders
Dou, Xiaozheng,Nath, Dinesh,Shin, Henry,Nurmemmedov, Elmar,Bourne, Philip C.,Ma, Jian-Xing,Duerfeldt, Adam S.
, p. 2854 - 2876 (2020/04/10)
Peroxisome proliferator-activated receptor alpha (PPARα) is expressed in retinal Müller cells, endothelial cells, and in retinal pigment epithelium; agonism of PPARα with genetic or pharmacological tools ameliorates inflammation, vascular leakage, neurodegeneration, and neovascularization associated with retinal diseases in animal models. As such, PPARα is a promising drug target for diabetic retinopathy and age-related macular degeneration. Herein, we report proof-of-concept in vivo efficacy in an streptozotocin-induced vascular leakage model (rat) and preliminary pharmacokinetic assessment of a first-generation lead 4a (A91). Additionally, we present the design, synthesis, and evaluation of second-generation analogues, which led to the discovery of 4u and related compounds that reach cellular potencies 2,700-fold selectivity for PPARα over other PPAR isoforms. These studies identify a pipeline of candidates positioned for detailed PK/PD and pre-clinical evaluation.
