91971-90-3Relevant academic research and scientific papers
Synthesis and biological evaluation of 3-arylbenzofuranone derivatives as potential anti-Alzheimer’s disease agents
Yang, Jie,Yun, Yinling,Miao, Yuhang,Sun, Jie,Wang, Xiaojing
, p. 805 - 814 (2020/03/23)
Multi-target drugs can better address the cascade of events involved in oxidative stress and the reduction in cholinergic transmission that occur in Alzheimer’s disease than cholinesterase inhibitors alone. We synthesised a series of 3-arylbenzofuranone derivatives and evaluated their antioxidant activity, cholinesterase inhibitory activity, and monoamine oxidase inhibitory activity. 3-Arylbenzofuranone compounds exhibit good antioxidant activity as well as selective acetylcholinesterase inhibitory activity. The IC50 value of anti-acetylcholinesterase inhibition of Compound 20 (0.089 ± 0.01 μM) is similar to the positive drug donepezil (0.059 ± 0.003 μM). According to the experimental results, Compounds 7, 13 show a certain effect in the in?vitro evaluation performed and have the potential as drug candidates for the treatment of Alzheimer’s disease.
Preparation method of 3,4,5-triethoxy phenylacetic acid
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Paragraph 0011; 0012; 0013; 0014; 0015; 0016, (2017/12/30)
The invention relates to a preparation method of 3,4,5-triethoxy phenylacetic acid. The preparation method is characterized by comprising the following steps: mixing a preheated 3,4,5-triethoxy benzaldehyde, a phase transfer catalyst, chloroform and a preheated alkaline solution into a channel reactor for reaction, adjusting the pH value of a water phase of reaction liquid by virtue of concentrated hydrochloric acid, and cooling for crystallization, so as to obtain 3,4,5-triethoxy mandelic acid or salt; adding 3,4,5-triethoxy mandelic acid or salt and sodium iodide into a polar aprotic solvent, preheating, and inputting the mixture and trimethylchlorosilane into a tubular reactor, so as to obtain a reaction solution; mixing the reaction solution with organic acid, mixing zinc powder with the polar aprotic solvent, and introducing the two mixtures into the channel reactor for reaction so as to obtain reaction liquid; and cooling the reaction liquid for crystallization, filtering, washing a filter cake, combining filtrate, washing, evaporating to obtain a solvent, and carrying out vacuum drying, so as to obtain 3,4,5-triethoxy phenylacetic acid. The preparation method has the advantages that the safety is high, the pollution is low, the cost is low, the yield is high, and the continuous production can be realized.
Isoquinolines as IGF-1R Inhibitors
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, (2009/04/24)
Compounds of the formula (I): were synthesized. In at least one embodiment, they were found to down-regulate or inhibit the expression or function of the IGF-1 receptor.
ISOQUINOLINES AS IGF-1R INHIBITORS
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Page/Page column 39, (2010/11/26)
Compounds of the formula (I) were synthesized. They were found to down- regulate or inhibit the expression or function of the IGF-I receptor.
Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships
Maryanoff,McComsey,Gardocki,Shank,Costanzo,Nortey,Schneider,Setler
, p. 1433 - 1454 (2007/10/02)
A series of pyrrolo[2,1-a]isoquinolines, and related compounds, were examined for antidepressant-like activity, by virtue of their antagonism of tetrabenazine-induced ptosis and sedation, and inhibition of biogenic amine uptake. Thus, we have identified some of the most potent antagonists of TBZ-induced ptosis and some of the most potent inhibitors of the uptake of dopamine, norepinephrine, and serotonin (in rat brain synaptosomes) ever reported. Compounds of particular note, in this regard, are 52b, 29b, 22b, and 48b, respectively. Biological activity was chiefly manifested by the trans isomeric class. Also, through resolution of four compounds, 7b, 24b, 37b, and 48b, biological activity was found to be associated with the (+) enantiomer subgroup (salts measured at 589 nm in MeOH), corresponding to the 6S,10bR absolute configuration for 7b, 37b, and 48b, and the 6R,10bR configuration for 24b. An X-ray determination on (+)-24b·HBr established its absolute configuration; configurations for the other compounds were verified by enantiospecific synthesis starting with (+)-(R)-2-phenylpyrrolidine. Regarding the pendant phenyl ring, diverse substitution patterns were investigated. Those substitutions that were particularly unfavorable were 3',4',5'-trimethoxy (20b), 2',3',4',5',6'-pentafluoro (34b), 2'-trifluoromethyl (38b), 3',5'-bis(trifluoromethyl) (42b), 4'-n-butyl (44b), 2'-cyano (47b), 4'-methylsulfonyl (50b), and 2'-carboxy (58b). Exceedingly potent compounds, in one way or another, were 10b-12b, 22b, 23b, 25b, 28b, 29b, 33b, 45b, 48b, 51b-53b. The pattern of aromatic substitution had a strong impact on selectivity in the uptake tests (NE vs. DA vs. 5-HT). Activity was significantly diminished by methyl substitution of 7b at the 5 (65, 66), 6 (61b), or 10b (60b) position, by changing the phenyl group of 7b to cyclohexyl (67b), benzyl (68b), or H (72), by moving the phenyl group of 7b to the 5 (69) or 10b (70) position, by expansion of ring B to an azepine (78b), and by modification of ring C to an azetidine (77b), piperidine (75b), or azepine (74b). The interaction of selected analogues with various CNS receptors is reported. Little affinity was shown for the muscarinic cholinergic receptor, suggesting a lack of anticholinergic side effects. Interestingly, 24b and 33b displayed a high affinity for the serotonin-2 receptor, analogous to mianserin and clomipramine. After the body of data was reviewed, derivatives 24b and 48b were chosen for advanced development.
