1441-87-8Relevant academic research and scientific papers
Synthesis of novel angular diazaphenoxazinone derivatives via palladium catalyzed Buchwald-Hartwig amidation protocols
Odaa,Okoro,Ugwu
, p. 3069 - 3073 (2015)
The synthesis of new amido derivatives of angular diazaphenoxazinone via tandem amidation protocol is reported. This was achieved by the condensation of 4,5-diamino-6-hydroxypyrimidine (7) with 2,3-dichloro-1,4-naphthoquinone (8) in anhydrous basic medium to furnish the key intermediate, 11-amino-6-chloro-8,10-diazabenzo[a]phenoxazin-5-one (9). Palladium catalyzed amidation reaction of 11-amino-6-chloro-8,10-diazabenzo[a]phenoxazin-5-one (9) with different amides (12a-c) (benzamide, acetamide, salicylamide and 4-nitrobenzamide) in the presence of palladium(II) acetate, triphenyl phosphine (PPh3), water and tertiary butanol at 110°C for 3 h gave the new amido derivatives 13a-c. Structures of the new compounds were established by elemental analysis, UV, FTIR, 1H NMR and 13C NMR.
Design and synthesis of novel 1,3,2-benzoxazaphosphinine-2-one derivatives: an in?vitro biological evaluation and in silico approaches
Sivala, Munichandra Reddy,Chintha, Venkataramaiah,Potla, Krishna Murthy,Kerru, Nagaraju,Chinnam, Sivakoteswararao,Devineni, Subba Rao,Salam J. J, Titinchi,Chinnam, Sampath,Chamarthi, Naga Raju
, p. 548 - 558 (2021)
A new class of benzoxazaphosphinine-2-one derivatives were synthesized by the reaction of 2-(3a,4,5,6,7,7a-hexahydro-1H-benzo[d]imidazol-2-yl)phenol with salicylic acid and thionyl chloride (SOCl2) via three-step process, and were obtained in good to excellent yields (77–95%) The designed compounds were evaluated for their in?vitro antioxidant, anti-fungal activities and in silico molecular docking. Amongst all, five compounds exhibited significant anti-fungal activity against F. oxysporum, A. niger and A. foetidus with MIC values displaying from 3.12 to 6.25 μg/mL correlated with standard drug Ketoconazole at 200 μg/mL. Furthermore, four compounds displayed promising antioxidant activity compared with the standard drugs butylated hydroxytoluene (BHT) and ascorbic acid in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) methods at 25, 50, 75 and 100 μg/mL. Molecular docking results disclosed that all the title compounds shown interesting binding modes with docking scores between ?6.6 and ?7.8 against the target 3MNG protein in comparison with standard drugs BHT (?5.1) and ascorbic acid (?5.5).
Novel derivatives of 5-amino-1-cyclopropyl-7-[(3R,5S)3,5- dimethylpiperazine-1-yl]-6,8-difluoro-4-oxo-quinoline-3-carboxylic acid: Their synthesis, antimicrobial, antifungal, and urease inhibitory studies
Arayne, M. Saeed,Sultana, Najma,Gul, Somia,Khan, Ajmal
, p. 1248 - 1256 (2014)
Sparfloxacin (SPFX) or 5-amino-1-cyclopropyl-7-[(3R,5S)3,5- dimethylpiperazine-1-yl]-6,8-difluoro-4-oxo-quinoline-3-carboxylic acid is an orally active synthetic, broad spectrum third generation quinolone, with excellent activity against Gram-positive bacteria with selectivity against anaerobes and atypical pathogens. Three derivatives of SPFX (2, 3, and 4) were synthesized by reacting different aromatic carboxylic acids with SPFX (1). Chemistry involved the formation of amide between reacting species through nucleophilic substitution reactions. The synthesized derivatives were then structurally characterized by IR, NMR, and mass spectroscopic techniques. The antimicrobial activities of these derivatives were evaluated against four Gram-positive, seven Gram-negative bacteria, and six fungi, using SPFX as a reference. Statistical analysis revealed these derivatives as active antimicrobial agents, and 2 was more potent antimicrobial agents than the parent drug as well other fluoroquinolones. Compounds 3 and 4 showed a significant activity against Fusarium solani. Moreover, these three derivatives were evaluated for inhibitory activities against enzyme urease, carbonic anhydrase II, and α-chymotrypsin. Results showed their selectivity against urease enzyme. Based on their nontoxic behavior, these derivatives may be potential agents for further studies.
Novel synthesis of a new surfactant 4-((4-bromophenyl)(dodecyl)amino)-4- oxobutanoic acid containing a benzene ring using a copper catalyst cross-coupling reaction and its properties
Chen, Minggui,Hu, Xinqi,Fu, Meilong
, p. 581 - 585 (2013)
A new surfactant 4-((4-bromophenyl)(dodecyl)amino)-4-oxobutanoic acid with a benzene spacer was synthesized via a novel copper catalyzed cross-coupling reaction. Its structure was confirmed by FTIR, 1H-NMR, 13C-NMR and HRMS; its purity was checked by HPLC. Dynamic light scattering and an atomic force microscope showed that it forms an unusual large-diameter premicellar aggregation below the CMC.
6,7-Dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinolines as superior reversal agents for P-glycoprotein-mediated multidrug resistance
Liu, Baomin,Qiu, Qianqian,Zhao, Tianxiao,Jiao, Lei,Li, Yunman,Huang, Wenlong,Qian, Hai
, p. 336 - 344 (2015)
P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy. Based on our previous study, 17 novel compounds with the 6,7-dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinoline scaffold were designed and synthesized. Among them, 2-[(1-{4-[2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl]phenyl}-1H-1,2,3-triazol-4-yl)methoxy]-N-(p-tolyl)-benzamide (compound 7h) was identified as a potent modulator of P-gp-mediated MDR, with high potency (EC50 = 127.5 ± 9.1 nM), low cytotoxicity (TI > 784.3), and long duration (> 24 h) in reversing doxorubicin (DOX) resistance in K562/A02 cells. Compound 7h also enhanced the effects of other MDR-related cytotoxic agents (paclitaxel, vinblastine, and daunorubicin), increased the accumulation of DOX and blocked P-gp-mediated rhodamine 123 efflux function in K562/A02 MDR cells. Moreover, 7h did not have any effect on cytochrome (CYP3A4) activity. These results indicate that 7h is a relatively safe modulator of P-gp-mediated MDR that has good potential for further development.
Uracil Hydroxybenzamides as Potential Antidiabetic Prodrugs
Brel’,Spasov,Lisina,Popov,Kucheryavenko,Litvinov,Salaznikova,Rashchenko
, p. 511 - 515 (2019)
A series of N1, N3-bis-hydroxybenzoyl, -acetoxybenzoyl, and -methoxybenzoyl uracil derivatives were synthesized. All compounds were screened for the ability to rupture protein cross links and antiglycating, chelating, and antiaggregant properties, which are most significant for pharmacological treatment of thrombosis and angio-, nephro-, encephalo-, and cardiopathies. 1,3-bis-(4-Methoxybenzoyl)pyrimidine-2,4(1H,3H)-dione was a promising antidiabetic agent with all studied activities.
Design, synthesis, and biological evaluation of 3′,4′,5′-trimethoxy evodiamine derivatives as potential antitumor agents
Peng, Yijiao,Xiong, Runde,Li, Zhen,Peng, Junmei,Xie, Zhi-Zhong,Lei, Xiao-Yong,He, Dongxiu,Tang, Guotao
, p. 1021 - 1032 (2021/02/26)
A series of compounds bearing 3′,4′,5′-trimethoxy module into the core structure of evodiamine were designed and synthesized. The synthesized compounds were screened in vitro for their antitumor potential. MTT results showed that compounds 14a–14c and 14i–14j had significant effects, with compound 14h being the most prominent, with an IC50 value of 3.3 ± 1.5?μM, which was lower than evodiamine and 5-Fu. Subsequent experiments further confirmed that compound 14h could inhibit cell proliferation and migration, and induce G2/M phase arrest to inhibit the proliferation of HGC-27 cells, which is consistent with the results of the cytotoxicity experiment. Besides, 14h could inhibit microtubule assembly and might kill tumor cells by inhibiting VEGF and glycolysis. All experimental results indicate that compound 14h might be a potential drug candidate for the treatment of gastric cancer and was worthy of further study.
Hydroxybenzoyl Chlorides in the Synthesis of Conjugates with Biologically Active Dipeptides
Brel, A. K.,Budaeva, Yu. N.,Lisina, S. V.
, p. 540 - 544 (2021/06/02)
Abstract: Conjugates of hydroxy- and acetoxybenzoic acids with dipeptides based on 4-aminobutanoic acid and glycine were synthesized through hydroxy(acetoxy)benzoyl chlorides and 4-[hydroxy(acetoxy)benzoyl-amino]butanoyl chlorides as intermediate products. Acyl chlorides were prepared by treatment of the corre-sponding acids with oxalyl chloride in the presence of dimethylformamide at a ratio of 1:1.1:0.07 in boiling benzene. The target N-[hydroxy(acetoxy)benzoyl] derivatives of dipeptides were obtained with high yields, and no further purification of the products was necessary. The synthesized compounds were evaluated as potential neuroprotective agents.
Novel propargylamine-based inhibitors of cholinesterases and monoamine oxidases: Synthesis, biological evaluation and docking study
Krátky, Martin,Vu, Quynh Anh,?těpánková, ?árka,Maruca, Annalisa,Silva, Tiago Barros,Ambro?, Martin,Pflégr, Václav,Rocca, Roberta,Svr?ková, Katarína,Alcaro, Stefano,Borges, Fernanda,Vin?ová, Jarmila
, (2021/09/07)
A combination of several pharmacophores in one molecule has been successfully used for multi-target-directed ligands (MTDL) design. New propargylamine substituted derivatives combined with salicylic and cinnamic scaffolds were designed and synthesized as potential cholinesterases and monoamine oxidases (MAOs) inhibitors. They were evaluated in vitro for inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE) using Ellman's method. All the compounds act as dual inhibitors. Most of the derivatives are stronger inhibitors of AChE, the best activity showed 5-bromo-N-(prop-2-yn-1-yl)salicylamide 1e (IC50 = 8.05 μM). Carbamates (4-bromo-2-[(prop-2-yn-1-yl)carbamoyl]phenyl ethyl(methyl)carbamate 2d and 2,4-dibromo-6-[(prop-2-yn-1-yl)carbamoyl]phenyl ethyl(methyl)carbamate 2e were selective and the most active for BuChE (25.10 and 26.09 μM). 4-Bromo-2-[(prop-2-yn-1-ylimino)methyl]phenol 4a was the most potent inhibitor of MAOs (IC50 of 3.95 and ≈10 μM for MAO-B and MAO-A, respectively) along with a balanced inhibition of both cholinesterases being a real MTDL. The mechanism of action was proposed, and binding modes of the hits were studied by molecular docking on human enzymes. Some of the derivatives also exhibited antioxidant properties. In silico prediction of physicochemical parameters affirm that the molecules would be active after oral administration and able to reach brain tissue.
Discovery of Novel Polycyclic Heterocyclic Derivatives from Evodiamine for the Potential Treatment of Triple-Negative Breast Cancer
Chen, Zhe-Sheng,Li, Dahong,Qiu, Yangyi,Wu, Liang,Xu, Jinyi,Xu, Shengtao,Yang, Dong-Hua,Yao, Hong,Zhou, Manzhen
, p. 17346 - 17365 (2021/12/09)
Evodiamine (Evo) is a quinazolinocarboline alkaloid found in Evodia rutaecarpa and exhibits moderate antiproliferative activity. Herein, we report using a scaffold-hopping approach to identify a series of novel polycyclic heterocyclic derivatives based on Evo as the topoisomerase I (Top1) inhibitor for the treatment of triple-negative breast cancer (TNBC), which is an aggressive subtype of breast cancer with limited treatment options. The most potent compound 7f inhibited cell growth in a human breast carcinoma cell line (MDA-MB-231) with an IC50 value of 0.36 μM. Further studies revealed that Top1 was the target of 7f, which directly induced irreversible Top1-DNA covalent complex formation or induced an oxidative DNA lesion through an indirect mechanism mediated by reactive oxygen species. More importantly, in vivo studies showed that 7f exhibited potent antitumor activity in a TNBC-patient-derived tumor xenograft model. These results suggest that compound 7f deserves further investigation as a promising candidate for the treatment of TNBC.
