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
Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity
Jia, Ruifang,Zhang, Jian,Bertagnin, Chiara,Cherukupalli, Srinivasulu,Ai, Wei,Ding, Xiao,Li, Zhuo,Zhang, Jiwei,Ju, Han,Ma, Xiuli,Loregian, Arianna,Huang, Bing,Zhan, Peng,Liu, Xinyong
, (2021/01/05)
Encouraged by our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Herein, we report the design, synthesis and biological evaluation of a series of novel oseltamivir derivatives via the structural modifications at C5–NH2 of oseltamivir targeting 150-cavity. Among them, compound 5c bearing 4-(3-methoxybenzyloxy)benzyl group exhibited the most potent activity, which was lower or modestly improved activities than oseltamivir carboxylate (OSC) against N1 (H1N1), N1 (H5N1) and N1 (H5N1–H274Y). Specifically, there was 30-fold loss of activity against the wild-type strain H1N1. However, 5c displayed 4.85-fold more potent activity than OSC against H5N1–H274Y NA. Also, 5c demonstrated low cytotoxicity in vitro and no acute toxicity in mice. Molecular docking studies provided insights into the high potency of 5c against N1 and N1–H274Y mutant NAs. Besides, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability of representative compounds were conducted to evaluate their drug-like properties.
Preparation method of safinamide mesylate intermediate
-
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.
Morpholine amide derivative and application thereof
-
Paragraph 0236; 0238-0241, (2020/12/14)
The invention discloses a morpholine amide derivative and application thereof, and particularly relates to a novel morpholine amide derivative and a pharmaceutical composition containing the compound.The invention also relates to a method for preparing th
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.
Potential anti-neuroinflammatory NF-кB inhibitors based on 3,4-dihydronaphthalen-1(2H)-one derivatives
Sun, Yue,Zhou, Yan-Qiu,Liu, Yin-Kai,Zhang, Hong-Qin,Hou, Gui-Ge,Meng, Qing-Guo,Hou, Yun
, p. 1631 - 1640 (2020/08/19)
Nuclear factor kappa B (NF-кB) inhibition represents a new therapeutic strategy for the treatment of neuroinflammatory diseases. In this study, a series of 3,4-dihydronaphthalen-1(2H)-one (DHN; 6a-n, 7a-c) derivatives were synthesised and characterised by NMR and HRMS. We assessed the toxicity and anti-neuroinflammatory properties of these compounds and found that 6m showed the greatest anti-neuroinflammatory properties, with relatively low toxicity. Specifically, 6m significantly reduced reactive oxygen species production, down-regulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 and prevented lipopolysaccharide-stimulated BV2 microglia cells polarisation towards an M1 phenotype. Furthermore, 6m significantly decreased IκBα and NF-кB p65 phosphorylation, thus inhibiting the NF-кB signalling pathway. This suggests that 6m may be explored as a functional anti-neuroinflammatory agent for the treatment of inflammatory diseases in the central nervous system, such as multiple sclerosis, traumatic brain injury, stroke and spinal cord injury.
PYRROLIDINEAMIDE DERIVATIVES AND USES THEREOF
-
Paragraph 00205, (2019/10/01)
Provided a pyrrolidineamide compound and a pharmaceutical composition containing this compound which can be used as a MAO-B inhibitor. Also provided methods of preparing this compound and pharmaceutical composition, and their use in the manufacture of a m
Alpha-aminoamide derivative and application thereof
-
Paragraph 0243; 0245; 0246; 0292; 0294; 0295, (2019/02/04)
The invention discloses an alpha-aminoamide derivative and application thereof. Specifically, the invention relates to a novel alpha-aminoamide derivative and a pharmaceutical composition containing the compound. The invention also relates to a method for
Nitrogen-containing heterocyclic amide derivative and use thereof
-
Paragraph 0254; 0256-0257, (2019/01/06)
The present invention discloses a nitrogen-containing heterocyclic amide derivative and use thereof, and in particular, the present invention relates to a novel class of nitrogen-containing heterocyclic amide derivatives and pharmaceutical compositions co
Phenolic compounds containing benzyloxy phenyl and preparation method and application of phenolic compounds
-
Paragraph 0374; 0375; 0376; 0377; 0378, (2017/09/19)
The invention discloses phenolic compounds (I) containing benzyloxy phenyl and a preparation method and application of the phenolic compounds. Pharmacological experiments prove that the phenolic compounds have high inhibiting activity on sphingosine kinase SphK, and part of the compounds has a certain inhibiting effect on inflammatory bowel disease induced by tumor and DSS. The phenolic compounds and the pharmaceutical preparations thereof can be used for preparing drugs for treating a series of cancer and inflammatory diseases such as colon cancer, lung cancer, breast cancer, liver cancer, stomach cancer, inflammatory bowel disease, hepatitis, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis and multiple sclerosis.
