5778-71-2Relevant articles and documents
Trapping of the highly strained [5](2,4)quinolinophane system
van Eis, Maurice J.,Lutz, Martin,Spek, Anthony L.,de Wolf, Willem H.,Bickelhaupt, Friedrich
, p. 1689 - 1694 (2007)
The highly strained [5](2,4)quinolinophane system can be generated as an intermediate (2b), which is extremely susceptible towards the attack of both nucleophilic and electrophilic species. Addition of water at the carbon bridgehead C2 occurs rapidly and is followed by rearrangements to give a strain free product 10. An unusual carbene addition at the N1{double bond, long}C2 bond of 2b is proposed to explain the formation of the strained 'anti-Bredt' type olefin 11.
New Hybrids of 4-Amino-2,3-polymethylene-quinoline and p-Tolylsulfonamide as Dual Inhibitors of Acetyl- And Butyrylcholinesterase and Potential Multifunctional Agents for Alzheimer’s Disease Treatment
Astakhova, Tatiana Yu.,Bachurin, Sergey O.,Boltneva, Natalia P.,Kovaleva, Nadezhda V.,Lushchekina, Sofya V.,Makhaeva, Galina F.,Palyulin, Vladimir A.,Proshin, Alexey N.,Radchenko, Eugene V.,Richardson, Rudy J.,Rudakova, Elena V.,Serkov, Igor V.
, (2020/09/17)
New hybrid compounds of 4-amino-2,3-polymethylene-quinoline containing different sizes of the aliphatic ring and linked to p-tolylsulfonamide with alkylene spacers of increasing length were synthesized as potential drugs for treatment of Alzheimer’s disease (AD). All compounds were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE. The lead compound 4-methyl-N-(5-(1,2,3,4-tetrahydro-acridin-9-ylamino)-pentyl)-benzenesulfonamide (7h) exhibited an IC50 (AChE) = 0.131 ± 0.01 μM (five times more potent than tacrine), IC50(BChE) = 0.0680 ± 0.0014 μM, and 17.5 ± 1.5% propidium displacement at 20 μM. The compounds possessed low activity against carboxylesterase, indicating a likely absence of unwanted drug-drug interactions in clinical use. Kinetics studies were consistent with mixed-type reversible inhibition of both cholinesterases. Molecular docking demonstrated dual binding sites of the conjugates in AChE and clarified the differences in the structure-activity relationships for AChE and BChE inhibition. The conjugates could bind to the AChE peripheral anionic site and displace propidium, indicating their potential to block AChE-induced β-amyloid aggregation, thereby exerting a disease-modifying effect. All compounds demonstrated low antioxidant activity. Computational ADMET profiles predicted that all compounds would have good intestinal absorption, medium blood-brain barrier permeability, and medium cardiac toxicity risk. Overall, the results indicate that the novel conjugates show promise for further development and optimization as multitarget anti-AD agents.
Design and synthesis of novel anti-Alzheimer's agents: Acridine-chromenone and quinoline-chromenone hybrids
Najafi, Zahra,Saeedi, Mina,Mahdavi, Mohammad,Sabourian, Reyhaneh,Khanavi, Mahnaz,Tehrani, Maliheh Barazandeh,Moghadam, Farshad Homayouni,Edraki, Najmeh,Karimpor-Razkenari, Elahe,Sharifzadeh, Mohammad,Foroumadi, Alireza,Shafiee, Abbas,Akbarzadeh, Tahmineh
, p. 84 - 94 (2016/07/06)
A novel series of acridine-chromenone and quinoline-chromenone hybrids were designed, synthesized, and evaluated as anti-Alzheimer's agents. All synthesized compounds were evaluated as cholinesterases (ChEs) inhibitors and among them, 7-(4-(6-chloro-2,3-d
