- Synthesis and screening of triazolopyrimidine scaffold as multi-functional agents for Alzheimer's disease therapies
-
In present study a series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d), strongly inhibited AChE with IC50 value of 42 nM. Furthermore compound 10d was identified as most promising compound with 12 fold selectivity against butyrylcholinesterase (BuChE). This compound displayed a composed multitargeted profile with promising inhibition of self-induced and AChE - induced Aβ aggregation and antioxidant activity.
- Kumar, Jitendra,Meena, Poonam,Singh, Anju,Jameel, Ehtesham,Maqbool, Mudasir,Mobashir, Mohammad,Shandilya, Ashutosh,Tiwari, Manisha,Hoda, Nasimul,Jayaram
-
p. 260 - 277
(2016/06/01)
-
- Quinoline-3-carboxamide containing sulfones as liver X receptor (LXR) agonists with binding selectivity for LXRβ and low blood-brain penetration
-
A series of quinoline-3-carboxamide containing sulfones was prepared and found to have good binding affinity for LXRβ and moderate binding selectivity over LXRα. The 8-Cl quinoline analog 33 with a high TPSA score, displayed 34-fold binding selectivity for LXRβ over LXRα (LXRβ IC50 = 16 nM), good activity for inducing ABCA1 gene expression in a THP macrophage cell line, desired weak potency in the LXRα Gal4 functional assay, and low blood-brain barrier penetration in rat.
- Hu, Baihua,Bernotas, Ron,Unwalla, Rayomand,Collini, Michael,Quinet, Elaine,Feingold, Irene,Goos-Nilsson, Annika,Wilhelmsson, Anna,Nambi, Ponnal,Evans, Mark,Wrobel, Jay
-
scheme or table
p. 689 - 693
(2010/06/14)
-
- QUINOLINE DERIVATIVES AS CASPASE-3 INHIBITOR, PREPARATION PROCESS FOR THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
-
Provided is a quinoline derivative represented by the following Formula (1) for use in treating a caspase- mediated disease by inhibition of caspase-3 activity. Further provided are a method for preparing the quinoline derivative or a pharmaceutically acceptable salt thereof and a pharmaceutical composition containing the same.
- -
-
Page/Page column 96-98
(2008/12/07)
-
- TRIAZOLE COMPOUNDS AS LIPOXYGENASE INHIBITORS
-
There is provided compounds of formula (I) wherein W is an optionally substituted aryl or heteroaryl group, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a lipoxygenase (e.g. 15- lipoxygenase) is desired and/or required, and particularly in the treatment of inflammation.
- -
-
Page/Page column 44
(2008/06/13)
-