4835-39-6Relevant articles and documents
Synthesis and biological evaluation of thiazolo and imidazo N-(4-nitrophenyl)-7-methyl-5-aryl-pyrimidine-6 carboxamide derivatives
Dhiman, Priyanka,Malik, Neelam,Verma, Prabhakar K.,Khatkar, Anurag
, p. 8699 - 8711 (2015)
Two new series of thiazolo and imidazo N-(4-nitrophenyl)-7-methyl-5-aryl-pyrimidine-6 carboxamide derivatives were synthesized. All the synthesized compounds were evaluated for their antimicrobial activity against Gram-positive bacteria: Staphylococcus aureus MTCC 3160, Bacillus subtilis MTCC 441, Gram-negative bacterium: Escherichia coli MTCC 443 and antifungal activity against Candida albicans MTCC 227 and Aspergillus Niger MTCC 281 and free radical scavenging activity. Compound 7e was found the most active antimicrobial comparable to standards taken. Compounds 7a, 7c, 9a, and 9d also showed significant antibacterial and antifungal activity. Further, compounds 7f, 9d, and 9h showed significant antioxidant activity with IC50 comparable with the standard compound. The synthesized compounds were confirmed for their structure by means of various spectrometric techniques like IR, 1H NMR, mass, and elemental analysis.
Novel 5-oxo-hexahydroquinoline derivatives: Design, synthesis, in vitro P-glycoprotein-mediated multidrug resistance reversal profile and molecular dynamics simulation study
Shahraki, Omolbanin,Edraki, Najmeh,Khoshneviszadeh, Mehdi,Zargari, Farshid,Ranjbar, Sara,Saso, Luciano,Firuzi, Omidreza,Miri, Ramin
, p. 407 - 418 (2017/02/26)
Overexpression of the efflux pump P-glycoprotein (P-gp) is one of the important mechanisms of multidrug resistance (MDR) in many tumor cells. In this study, 26 novel 5-oxo-hexahydroquinoline derivatives containing different nitrophenyl moieties at C4 and various carboxamide substituents at C3 were designed, synthesized and evaluated for their ability to inhibit P-gp by measuring the amount of rhodamine 123 (Rh123) accumulation in uterine sarcoma cells that overexpress P-gp (MES-SA/Dx5) using flow cytometry. The effect of compounds with highest MDR reversal activities was further evaluated by measuring the alterations of MES-SA/Dx5 cells’ sensitivity to doxorubicin (DXR) using MTT assay. The results of both biological assays indicated that compounds bearing 2-nitrophenyl at C4 position and compounds with 4-chlorophenyl carboxamide at C3 demonstrated the highest activities in resistant cells, while they were devoid of any effect in parental nonresistant MES-SA cells. One of the active derivatives, 5c, significantly increased intracellular Rh123 at 100 μM, and it also significantly reduced the IC50 of DXR by 70.1% and 88.7% at 10 and 25 μM, respectively, in MES-SA/Dx5 cells. The toxicity of synthesized compounds against HEK293 as a noncancer cell line was also investigated. All tested derivatives except for 2c compound showed no cytotoxicity. A molecular dynamics simulation study was also performed to investigate the possible binding site of 5c in complex with human P-gp, which showed that this compound formed 11 average H-bonds with Ser909, Thr911, Arg547, Arg543 and Ser474 residues of P-gp. A good agreement was found between the results of the computational and experimental studies. The findings of this study show that some 5-oxo-hexahydroquinoline derivatives could serve as promising candidates for the discovery of new agents for P-gp-mediated MDR reversal.
Design, Multicomponent Synthesis and Characterization of Diversely Substituted Pyrazolo[1,5-a] Pyrimidine Derivatives
Ghelani, Satish M.,Naliapara, Yogesh T.
, p. 1843 - 1851 (2016/11/23)
The synthesis of various heterocyclic compounds using acetoacetanilide[AAA], we have demonstrated that acetoactanilide are versatile intermediate for the synthesis of pyrazolopyrimidine derivatives. Thus, to explore further, we sought that the reaction of various acetoactanilide, an appropriate aldehyde and 5-amino-N-cyclohexyl-3-(methylthio)-1H-pyrazole-4-carboxamide in the presence of base in isopropyl alcohol could be an effective strategy to furnish the novel pyrazolopyrimidine derivatives. Here we describe the novel synthetic methodology for the fused pyrazolopyrimidines.
