6268-00-4Relevant academic research and scientific papers
Design, synthesis and investigation of new diphenyl substituted pyridazinone derivatives as both cholinesterase and Aβ-aggregation inhibitors
Kilic, Burcu,Erdogan, Merve,Gulcan, Hayrettin O.,Aksakal, Fatma,Oruklu, Nihan,Bagriacik, Emin U.,Dogruer, Deniz S.
, p. 59 - 76 (2019/06/11)
Background: With respect to the increase in the average life expectancy, Alzheimer Disease (AD), the most common form of age-related dementia, has become a major threat to the population over the age of 65 during the past several decades. The majority of AD treatments are focused on cholinergic and amyloid hypotheses. Objective: In this study, three series of diphenyl-2-(2-(4-substitutedpiperazin-1-yl)ethyl)pyridazin- 3(2H)-one derivatives were designed, synthesized and investigated for their ability to inhibit both cholinesterase enzymes and amyloid-β aggregation. Method: The inhibitory activities of the synthesized compounds on AChE (from electric eel) and BChE (from equine serum) were determined by the modified Ellman’s method. The reported thioflavin T-based fluorometric assay was performed to investigate the effect of the selected compounds on the aggregation of Aβ1-42. The cytotoxic effect of the compounds (4g, 11g and 18g) was monitored in 3T3 cell lines to gain insight into therapeutic potential of the compounds by using MTT assay. The crystal structures of the AChE (1EVE) and BChE (1P0I) enzymes were retrieved from the RCSB Protein Data Bank and Molecular Operating Environment (MOE) software was used for molecular docking of the ligands. Results: Among the tested compounds, 5,6-diphenyl derivative 18g was identified as the most potent and selective AChE inhibitor (IC50 = 1.75 μM, Selectivity Index for AChE > 22.857). 4,6- Diphenyl derivative 11g showed the highest and the most selectivity for BChE (IC50= 4.97 μM, SI for AChE 0.124). Interestingly, 4,5-diphenyl derivative 4g presented dual cholinesterase inhibition (AChE IC50= 5.11 μM; BChE IC50= 14.16 μM, SI for AChE = 2.771). Conclusion: Based on biological activity results and low toxicity of the compounds, it can be said that diphenyl substituted pyridazinone core is a valuable scaffold. Especially, dual inhibitory potencies of 4,5-diphenylpyridazin-3(2H)-one core for the cholinesterase enzymes and Aβ- aggregation makes this core a promising disease-modifying agent.
Cyano-borrowing reaction: Nickel-catalyzed direct conversion of cyanohydrins and aldehydes/ketones to β-cyano ketone
Li, Zhao-Feng,Li, Qian,Ren, Li-Qing,Li, Qing-Hua,Peng, Yun-Gui,Liu, Tang-Lin
, p. 5787 - 5792 (2019/06/17)
A direct nickel-catalyzed, high atom- and step-economical reaction of cyanohydrins with aldehydes or ketones via an unprecedented "cyano-borrowing reaction" has been developed. Cleavage of the C-CN bond of cyanohydrins followed by aldol condensation and conjugate addition of cyanide to α,β-unsaturated ketones proceeded to deliver a range of racemic β-cyano ketones with good to high yields. The practical procedure with the use of a commercial and less-toxic CN source bodes well for wide application of this protocol.
Tetraarylphosphonium inner-salts (TAPIS) as both Lewis base catalyst and phase tag
Guo, Shuhui,Mi, Xueling
supporting information, p. 2881 - 2884 (2017/07/11)
Tetraarylphosphonium inner-salts (TAPIS) have been designed, synthesized and verified as recyclable and reusable Lewis base catalysts. The resulted TAPIS catalyst has been successfully applied in Michael addition, cyanation and trifluoromethylation reactions.
Conjugate Hydrocyanation of Chalcone Derivatives Using Ethyl Cyanoacetate as an Organic Cyanide Source
Li, Zheng,Yin, Junjun
, p. 1179 - 1184 (2017/07/24)
The conjugate hydrocyanation of chalcone derivatives using ethyl cyanoacetate as an organic cyanide source at room temperature under open air and transition metal-free conditions was described. The protocol has advantages of using relatively cheap, less toxic, stable and easy-to-handle cyanating reagent, high yield, and mild reaction condition.
Functionalised diimidazolium salts: The anion effect on the catalytic ability
Rizzo, Carla,D'Anna, Francesca,Noto, Renato
, p. 58477 - 58484 (2016/07/07)
The catalytic ability of some functionalised diimidazolium ionic liquids was tested using the Michael addition of malononitrile to t-chalcone as probe reaction. Diimidazolium salts characterized by the presence of 1-(1-imidazolylmethyl)-3,5-di-[1-(3-octylimidazolylmethyl)]benzene cation and differing in the anion structure were used. Both mono- and dianions were employed and among these some chiral anions generally used as organocatalysts were taken into account. Data collected were analysed both as function of ionic liquids structure and basicity, evaluated using the Hammett basicity function. Although the use of chiral anions did not allow performing a stereochemical control of the reaction, data collected demonstrate the high catalytic ability of the functionalised salts. Indeed, high conversions and yields were obtained under mild conditions and in significantly shorter reaction times with respect to the ones so far reported for this reaction.
Enantioselective conjugate addition of cyanide to chalcones catalyzed by a magnesium-Py-BINMOL complex
Dong, Cheng,Song, Tao,Bai, Xing-Feng,Cui, Yu-Ming,Xu, Zheng,Xu, Li-Wen
, p. 4755 - 4759 (2015/10/05)
An enantioselective magnesium-catalyzed conjugate addition of trimethylsilyl cyanide to chalcones in the presence of Py-BINMOL with multiple stereogenic centers, through dual activation of substrates, has been successfully developed with moderate to good enantioselectivities and in good yields.
Thiourea-functionalized magnetic hydroxyapatite as a recyclable inorganic-organic hybrid nanocatalyst for conjugate hydrocyanation of chalcones with TMSCN
Oskouie, Afsaneh Arefi,Taheri, Salman,Mamani, Leila,Heydari, Akbar
, p. 6 - 10 (2015/09/21)
The recoverable nanomagnetic catalyst was manufactured based on thiourea modified magnetic hydroxyapatite. Magnetic hydroxyapatite (mHAp) as the inorganic-organic hybrid support was fabricated using co-precipitate condition and then modified via the covalently anchoring of 1-(3,5-bis(trifluoromethyl)phenyl-3-propyl)thiourea. The hybrid nano-catalyst has been identified by TEM, SEM, FTIR, BET, TGA, and XRD. This nanocatalyst appeared efficient and robust in the 1,4-addition reaction of TMSCN to α,β-unsaturated aromatic enones in excellent yields (85-96%) under mild reaction condition and simple work-up process. This recoverable organocatalyst has a great potential as an industrially viable and eco-safe catalyst.
Synthesis of multisubstituted 1H-pyrrole: Selenium-catalyzed reaction of γ-nitro substituted carbonyl compounds and carbon monoxide
Umeda, Rui,Mashino, Tsukasa,Nishiyama, Yutaka
, p. 4395 - 4399 (2014/06/10)
The novel and efficient selenium-catalyzed reductive N-heterocyclization of γ-nitro substituted carbonyl compounds with carbon monoxide has been developed. Various multisubstituted 1H-pyrroles can be easily prepared by this protocol. The one-pot synthesis
Synthesis of β-cyanopropan-1-one derivates by domino reaction
Dong, Hong-Ru,Dong, Wang-Jun,Li, Rong-Shan,Hu, Yi-Ming,Dong, Heng-Shan,Xie, Zhi-Xiang
supporting information, p. 3454 - 3457 (2014/07/08)
Domino nucleophilic addition was used for four-component Al 2O3-catalyzed environmentally friendly synthesis of polysubstituted β-cyanopropan-1-one. Domino nucleophilic addition involves removal of the cyano group linked to active methylene by the action of KF, and direct addition to enones. The reaction's capability for nucleophilic attack is F- > CN- in DMF. The use of low-toxicity reagents hints that the reaction is more environmentally friendly than traditional approaches. This journal is the Partner Organisations 2014.
