5356-71-8Relevant academic research and scientific papers
One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents
Abdel-Aziz, Hatem A.,Barghash, Reham F.,Eldehna, Wagdy M.,Kovalová, Markéta,Kry?tof, Vladimír,Vojá?ková, Veronika
, (2021/11/04)
In the current study, we report on the development of novel series of pyrazolo[3,4-b]pyridine derivatives (8a-u, 11a-n, and 14a,b) as potential anticancer agents. The prepared pyrazolo[3,4-b]pyridines have been screened for their antitumor activity in vitro at NCI-DTP. Thereafter, compound 8a was qualified by NCI for full panel five-dose assay to assess its GI50, TGI and LC50 values. Compound 8a showed broad-spectrum anti-proliferative activities over the whole NCI panel, with outstanding growth inhibition full panel GI50 (MG-MID) value equals 2.16 μM and subpanel GI50 (MG-MID) range: 1.92–2.86 μM. Furthermore, pyrazolo[3,4-b]pyridines 8a, 8e-h, 8o, 8u, 11a, 11e, 11h, 11l and 14a-b were assayed for their antiproliferative effect against a panel of leukemia cell lines (K562, MV4-11, CEM, RS4;11, ML-2 and KOPN-8) where they possessed moderate to excellent anti-leukemic activity. Moreover, pyrazolo[3,4-b]pyridines 8o, 8u, 14a and 14b were further explored for their effect on cell cycle on RS4;11 cells, in which they dose-dependently increased populations of cells in G2/M phases. Finally we analyzed the changes of selected proteins (HOXA9, MEIS1, PARP, BcL-2 and McL-1) related to cell death and viability in RS4;11 cells via Western blotting. Collectively, the obtained results suggested pyrazolo[3,4-b]pyridines 8o, 8u, 14a and 14b as promising lead molecules for further optimization to develop more potent and efficient anticancer candidates.
Mechanistic selectivity investigation and 2D-QSAR study of some new antiproliferative pyrazoles and pyrazolopyridines as potential CDK2 inhibitors
Hassan, Ghaneya S.,Georgey, Hanan H.,Mohammed, Esraa Z.,George, Riham F.,Mahmoud, Walaa R.,Omar, Farghaly A.
, (2021/04/02)
Novel series of diphenyl-1H-pyrazoles (4a-g) and pyrazolo[3,4-b]pyridines (5a-g and 7a-i) were synthesized and evaluated for their antiproliferative activity against breast cancer cell line (MCF7) and Hepatocellular carcinoma cell line (HepG2). The highest MCF7 growth inhibition activity was attained via compounds 4f and 7e (IC50 = 1.29 and 0.93 μM, respectively), while compounds 5b and 7f were the most active ones against HepG2 (IC50 = 1.57 and 1.33 μM, respectively) compared to doxorubicin (IC50 = 1.88 and 7.30 μM, respectively). Cell cycle analysis showed arrest at S and G2-M phases in MCF7 cells treated with 4f and 7e, and at G2-M and G1/S phases in HepG2 cells treated with 5b and 7f, respectively. Apoptotic effect of compounds 4f, 5b, 7e, and 7f was indicated via their pre-G1 early and late apoptotic effects and augmented levels of caspase-9/MCF7 and caspase-3/HepG2. A worthy safety profile was assessed for compounds 4f and 7e on MCF10A and compounds 5b and 7f on THLE2 treated normal cells. Furthermore, compounds 4f, 5b and 7f displayed a promising selective profile for CDK2 inhibition vs. CDK1, CDK4, and CDK7 isoforms as proved from their selectivity index. Docking in CDK2 ATP binding site, co-crystallized with R-Roscovitine, demonstrated analogous interactions and comparable binding energy with the native ligand. 2D QSAR sighted the possible structural features governing the CDK2 inhibition activity elicited by the studied pyrazolo[3,4-b]pyridines. These findings present compounds 4f, 5b, and 7f as selective CDK2 inhibitors with promising antiproliferative activity against MCF7 and HepG2 cancer cells.
Visible-light enabled C4-thiocyanation of pyrazoles by graphite-phase carbon nitride (g-C3N4)
Pan, Junyi,Liu, Cheng,Wang, Jianqiang,Dai, Yunqiao,Wang, Shengyu,Guo, Cheng
supporting information, (2021/07/14)
Thiocyanation is an important and effective way to form C[sbnd]S bonds in organic synthetic methodology. Especially, thiocyanation of pyrazole attracts the attention of many researchers because sulfur-containing compounds are widely applied in many crucial fields such as organic materials, agrochemistry, nanotechnology, etc. Herein, we described A rapid metal- and additive-free method for C(sp2)-H thiocyanation of pyrazoles under visible light at room temperature by using a sustainable catalyst of graphite-phase carbon nitride (g-C3N4) and a thiocyanating agent of ammonium thiocyanate. The method presents many advantages, such as usage of eco-friendly photoredox catalyst, a wide range of substrates and a good yield of products, etc.
Synthesis, in vitro anticancer activity and in silico studies of certain pyrazole-based derivatives as potential inhibitors of cyclin dependent kinases (CDKs)
George, Riham F.,Georgey, Hanan H.,Hassan, Ghaneya S.,Mahmoud, Walaa R.,Mohammed, Esraa Z.,Omar, Farghaly A.
, (2021/09/24)
New diphenyl-1H-pyrazoles were synthesized and screened for CDK2 inhibition where 8d, 9b, 9c, and 9e exhibited promising activity (IC50 = 51.21, 41.36, 29.31, and 40.54 nM respectively) compared to R-Roscovitine (IC50 = 43.25 nM). Furthermore, preliminary anti-proliferative activity screening of some selected compounds on 60 cancer cell lines was performed at the (NCI/USA). Compounds 8a-c displayed promising growth inhibitory activity (mean %GI; 73.74, 94.32 and 74.19, respectively). Additionally, they were further selected by the NCI for five-dose assay, exhibiting pronounced activity against almost the full panel (GI50 ranges; 0.181–5.19, 1.07–4.12 and 1.07–4.82 μM, respectively) and (Full panel GI50 (MG-MID); 2.838, 2.306 and 2.770 μM, respectively). Screening the synthesized compounds 8a-c for inhibition of CDK isoforms revealed that compound 8a exhibited nearly equal inhibition to all the tested CDK isoforms, while compound 8b inhibits CDK4/D1 preferentially than the other isoforms and compound 8c inhibits CDK1, CDK2 and CDK4 more than CDK7. Flow cytometry cell cycle assay of 8a-c on Non-small cell lung carcinoma (NSCL HOP-92) cell line revealed S phase arrest by 8a and G1/S phase arrest by 8b and 8c. Apoptotic induction in HOP-92 cell line was also observed upon treatment with compounds 8a-c. Docking to CDK2 ATP binding site revealed similar interactions as the co-crystallized ligand R-Roscovitine (PDB code; 3ddq). These findings present compounds 8a-c as promising anti-proliferative agents.
Novel aminopyrazole tagged hydrazones as anti-tubercular agents: Synthesis and molecular docking studies
Padmini, Thatavarthi,Bhikshapathi, Darna,Suresh, Kandagatla,Kulkarni, Ravindra,Kamal, Bigala Raj
, p. 344 - 351 (2021/03/08)
Background: Pyrazole derivatives have been reported to possess numerous pharmacological activities viz., anti-inflammatory, antipsychotic, etc. Our group has disclosed that pyrazole benzamides display potent antibacterial and anti-tubercular activities. O
Highly Efficient Chemoselective Synthesis of Pyrrolo[2,3- c ]pyrazole Bearing Oxindole via Sequential Condensation-Michael Addition-Intramolecular Cyclization Reactions
Farhid, Hassan,Javanbakht, Siamak,Nazeri, Mohammad Taghi,Notash, Behrouz,Shaabani, Ahmad
supporting information, p. 965 - 971 (2020/06/10)
An efficient and highly chemoselective approach for the synthesis of novel scaffolds based on pyrrolo[2,3- c ]pyrazole bearing oxindole is accomplished by the acid-promoted sequential reactions between benzoylacetonitriles, phenylhydrazine, and 3-phenacyl
Organocatalytic Enantioselective Aminoalkylation of 5-Aminopyrazole Derivatives with Cyclic Imines
Carceller-Ferrer, Laura,González del Campo, Aleix,Vila, Carlos,Blay, Gonzalo,Mu?oz, M. Carmen,Pedro, José R.
supporting information, p. 7450 - 7454 (2020/11/30)
In this communication, an efficient asymmetric aminoalkylation of 5-aminopyrazole derivatives with cyclic benzoxathiazine 2,2-dioxides catalyzed by a quinine-derived squaramide in dichloromethane has been established. This is the first example of 5-aminopyrazole derivatives in asymmetric catalysis. A variety of chiral sulfamidates bearing an aminopyrazole moiety were obtained in good yields (up to 98 %) and moderate to excellent enantioselectivities (up to 99 %ee).
Microwave synthesis of 1-aryl-1H-pyrazole-5-amines
Everson, Nikalet,Yniguez, Kenya,Loop, Lauren,Lazaro, Horacio,Belanger, Briana,Koch, Grant,Bach, Jordan,Manjunath, Aashrita,Schioldager, Ryan,Law, Jarvis,Grabenauer, Megan,Eagon, Scott
supporting information, p. 72 - 74 (2018/11/30)
A microwave-mediated synthesis of 1H-pyrazole-5-amines utilizing 1 M HCl at 150 °C was developed in order to provide products in a matter of minutes with minimal purification. Most reactions are complete in only 10 min and can be isolated via a simple filtration without the need for further purification by column chromatography or recrystallization. This method tolerates a range of functional groups and can be performed on milligram to gram scales.
Synthesis of new conjugates 1H-Pyrazolo[3,4-b]pyridine-phosphoramidate and evaluation against leishmania amazonensis
Medeiros, Antonia C. R. F.,Borges, Julio C.,Becker, Klaus M.,Rodrigues, Raquel F.,Leon, Leonor L.,Canto-Cavalheiro, Marilene,Bernardino, Alice M. R.,De Souza, Marcos C.,Pedrosa, Leandro F.
, p. 159 - 167 (2017/12/08)
In this research three series of substituted 1H-pyrazolo[3,4-b]pyridine phosphoramidates were synthesized and characterized by infrared,1H,13C, and31P nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. The products were obtained in good yields (67-83percent) under mild conditions by nucleophilic aromatic substitution reaction of aminoalkylphosphoramidates over 4-chloro-1H-pyrazolo[3,4-b]pyridines. These compounds were evaluated as antileishmanials against Leishmania amazonensis promastigotes in vitro. Among all, compounds of a series showed expressive antileishmanial activity. Two of them emerged as the most active, with IC50 values of 6.44 ± 1.49 and 12.25 ± 0.68 μM. The cytotoxicity of this series was assessed on murine cells and presented values similar to the reference drug pentamidine.
Multi-component synthesis of 3-substituted indoles and their cyclisation to α-carbolines: Via I2-promoted intramolecular C2 oxidative amination/aromatisation at room temperature
Deka, Bhaskar,Baruah, Pranjal K.,Deb, Mohit L.
supporting information, p. 7806 - 7810 (2018/11/21)
Condensation of indoles, aldehydes and pyrazol-5-amine in the presence of ceric ammonium nitrate gives 3-substituted indoles. These then cyclise to α-carbolines at room temperature through I2-promoted intramolecular C2 amination and aromatisation in open air. A plausible mechanism is proposed based on some controlled experiments.
