1878-49-5Relevant articles and documents
Optimization of NAMPT activators to achieve in vivo neuroprotective efficacy
Hua, Lan,Liu, Minghui,Liu, Yang,Lu, Haigen,Ma, Weinan,Tang, Yefeng,Wang, Gelin,Wang, Leibo,Wu, Chou,Xi, Shuang,Yao, Hong,Zhang, Ruoxi,Zu, Yumeng
, (2022/04/07)
NAMPT is the rate-limiting enzyme in the NAD salvage pathway, which makes it an attractive target for the treatment of many diseases associated with NAD exhaustion such as neurodegenerative diseases. Herein, we present the systematic optimization of NAT, an initial hit of NAMPT activator discovered by us through high-throughput screening, based on the co-crystal structure of the NAMPT-NAT complex. Over 80 NAT derivatives have been designed and synthesized, among which compound 72 showed notably improved potency as NAMPT activator and effectively protected cultured cells from FK866-mediated toxicity. Moreover, compound 72 exhibited strong neuroprotective efficacy in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN) without any overt toxicity, which renders it a promising candidate for the development of novel neuroprotective agents.
Method for preparing 2-methyl-4-chlorophenoxyacetic acid through catalytic chlorination of 2-methylphenoxyacetic acid
-
Paragraph 0041; 0044-0045, (2021/03/13)
The invention relates to a preparation method of 2-methyl-4-chlorophenoxyacetic acid, in particular to a method for preparing 2-methyl-4-chlorophenoxyacetic acid through catalytic chlorination of 2-methylphenoxyacetic acid. The method comprises the following steps: by taking o-methylphenoxyacetic acid (MPA) as a raw material, performing a reaction in the presence of chlorine by virtue of a catalyst, and filtering, so as to obtain the 2-methyl-4-chlorophenoxyacetic acid (MCPA), wherein the catalyst is imidazole ionic liquid. By means of the catalyst, the reaction activity is relatively high, the o-methyl phenoxyacetic acid is subjected to catalytic chlorination reaction, and the 2-methyl-4-chlorophenoxyacetic acid is prepared at a high yield; besides, compared with existing literature reports, the reaction system is simple and convenient to operate, no wastewater is generated in the chlorination step, a high-quality product can be obtained, and large-scale production is facilitated.
2-methyl-4-chlorophenoxyacetic acid preparation method
-
Page/Page column 7-13, (2019/08/01)
The invention provides a 2-methyl-4-chlorophenoxyacetic acid preparation method, which comprises: carrying out a condensation reaction on sodium o-cresolate and sodium chloroacetate under the catalysis of a trimethylamine catalyst to obtain 2-methyl sodium phenoxyacetate, acidifying, and chlorinating to obtain 2-methyl-4-chlorophenoxyacetic acid. According to the present invention, under the catalysis of the trimethylamine catalyst, sodium o-cresolate and sodium chloroacetate can be subjected to the condensation reaction in the near-neutral environment with the temperature of lower than 70 DEGC, such that the main side reaction for hydrolyzing sodium chloroacetate into sodium glycolate is greatly reduced, the produced wastewater contains less o-methylphenol and glycolic acid (or sodium glycolate) so as to easily meet the nationally acceptable emission standards at a low treatment cost, the resource utilization of the waste acid solution can be achieved, the cost of the raw materials and the three-waste treatment cost are reduced, the purity of 2-methyl-4-chlorophenoxyacetic acid is higher than 95%, and the total yield is higher than 93%.