129747-73-5Relevant academic research and scientific papers
Method for preparing substituted thiophenol and heterocyclic thiophenol by continuous flow reactor
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Paragraph 0045-0046; 0049-0050; 0051-0052; 0055-0056, (2019/01/14)
The invention relates to a method for preparing substituted thiophenol and heterocyclic thiophenol by a continuous flow reactor. Phenol and phenol derivatives or heterocyclic phenol are taken as starting materials, and target compounds are prepared by four-step reactions of chlorination, esterification, rearrangement and hydrolysis, wherein the rearrangement reaction is conducted in the continuousflow reactor. According to the method, the reaction is guaranteed by a miniaturized heating device for high-temperature reaction and heat generated by the reaction, the conversion rate and the yieldhigher than those in the conventional reactor are obtained in the short residence time of tens of seconds, relevant side reactions are reduced, meanwhile, fluctuation of temperature and concentrationis avoided in the reaction process, temperature run-away and overheat are avoided, and the reaction process is safe and controllable.
Development of a novel series of styrylquinoline compounds as high- affinity leukotriene D4 receptor antagonists: Synthetic and structure- activity studies leading to the discovery of (±)-3-[[[3-[2-(7-chloro-2- quinolinyl)-(E)-ethenyl]phenyl][[3-(dimethylamino)-3- oxopropyl]thio]methyl]thio]propionic acid
Zamboni,Belley,Champion,Charette,DeHaven,Frenette,Gauthier,Jones,Leger,Masson,McFarlane,Metters,Pong,Piechuta,Rokach,Therien,Williams,Young
, p. 3832 - 3844 (2007/10/02)
Based on LTD4 receptor antagonist activity of 3-(2-quinolinyl-(E)- ethenyl)pyridine (2) found in broad screening, structure-activity studies were carried out which led to the identification of 3-[[[3-[2-(7-chloro-2- quinolinyl)-(E)-ethenyl]phenyl][[3-(dimethylamino)-3- oxopropyl]thio]methyl]thio]propionic acid (1, MK-571) as a potent and orally active LTD4 receptor antagonist. These studies demonstrated that a phenyl ring could replace the pyridine in 2 without loss of activity, that 7-halogen substitution in the quinoline group was optimal for binding, that the (E)- ethenyl linkage was optimal, that binding was enhanced by incorporation of a polar acidic group or groups in the 3-position of the aryl ring, and that two acidic groups could be incorporated via a dithioacetal formed from thiopropionic acid and the corresponding styrylquinoline 3-aldehyde to yield compounds such as 20 (IC50 = 3 nM vs [3H]LTD4 binding to the guinea pig lung membrane). It was found that one of the acidic groups could be transformed into a variety of the amides without loss of potency and that the dimethylamide 1 embodied the optimal properties of intrinsic potency (IC50 = 0.8 nM on guinea pig lung LTD4 receptor) and oral in vivo potency in the guinea pig, hyperreactive rat, and squirrel monkey. The evolution of 2 to 1 involves the increase of >6000-fold in competition for [3H]LTD4 binding to guinea pig lung membrane and a >40-fold increase in oral activity as measured by inhibition of antigen-induced dyspnea in hyperreactive rats.
