103205-34-1Relevant academic research and scientific papers
Novel synthesis method of bromfenac sodium
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Paragraph 0073-0080; 0112-0119; 0151-0158, (2021/11/27)
The novel synthesis method is characterized by comprising the following steps: taking o-aminophenylacetic acid as a starting raw material, and performing acylation reaction to obtain the intermediate I. The intermediate I is subjected to a sulfonation reaction to obtain an intermediate II. The intermediate II is reacted with p-bromobenzoyl chloride to give an intermediate III. The intermediate III is hydrolyzed to give bromfenac. The final finished product bromfenac sodium is obtained by reacting bromfenac and sodium hydroxide. The method has the beneficial effects that an indole ring-containing impurity generated due to a synthetic method in the prior art is avoided. The problem of exceeding standard of final finished product pH caused by using phosphoric acid or glacial acetic acid to produce acid salt in the prior art is avoided.
Pharmacomodulation of the antimalarial plasmodione: Synthesis of biaryl-and N-arylalkylamine analogues, antimalarial activities and physicochemical properties
Urgin, Karène,Jida, Mouhamad,Ehrhardt, Katharina,Müller, Tobias,Lanzer, Michael,Maes, Louis,Elhabiri, Mourad,Davioud-Charvet, Elisabeth
, (2017/02/15)
With the aim of increasing the structural diversity on the early antimalarial drug plasmodione, an efficient and versatile procedure to prepare a series of biaryl- and N-arylalkylamines as plasmodione analogues is described. Using the naturally occurring and commercially available menadione as starting material, a 2-step sequence using a Kochi-Anderson reaction and subsequent Pd-catalyzed Suzuki-Miyaura coupling was developed to prepare three representative biphenyl derivatives in good yields for antimalarial evaluation. In addition, synthetic methodologies to afford 3-benzylmenadione derivatives bearing a terminal -N(Me)2 or -N(Et)2 in different positions (ortho, meta and para) on the aryl ring of the benzylic chain of plasmodione were investigated through reductive amination was used as the optimal route to prepare these protonable N-arylalkylamine privileged scaffolds. The antimalarial activities were evaluated and discussed in light of their physicochemical properties. Among the newly synthesized compounds, the para-position of the substituent remains the most favourable position on the benzyl chain and the carbamate -NHBoc was found active both in vitro (42 nM versus 29 nM for plasmodione) and in vivo in Plasmodium berghei-infected mice. The measured acido-basic features of these new molecules support the cytosol-food vacuole shuttling properties of non-protonable plasmodione derivatives essential for redox-cycling. These findings may be useful in antimalarial drug optimization.
