4640-67-9Relevant academic research and scientific papers
One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents
Barghash, Reham F.,Eldehna, Wagdy M.,Kovalová, Markéta,Vojá?ková, Veronika,Kry?tof, Vladimír,Abdel-Aziz, Hatem A.
, (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.
Asymmetric Hydroacylation Involving Alkene Isomerization for the Construction of C3-Chirogenic Center
Liu, Chong,Yuan, Jing,Zhang, Zhenfeng,Gridnev, Ilya D.,Zhang, Wanbin
supporting information, p. 8997 - 9002 (2021/03/16)
A new transformation pattern for enantioselective intramolecular hydroacylation has been developed involving an alkene isomerization strategy. Proceeding through a five-membered rhodacycle intermediate, 3-enals were converted to C3- or C3,C5-chirogenic cyclopentanones with satisfactory yields, diastereoselectivities, and enantioselectivities. A catalytic cycle has been theoretically calculated and the origin of the stereoselection is rationally explained.
Modular synthesis and antiproliferative activity of new dihydro-1H-pyrazolo[1,3-b]pyridine embelin derivatives
Amesty, ángel,Estévez-Braun, Ana,Fernández-Pérez, Leandro,Guerra, Borja,Guerra-Rodríguez, Miguel,Martín-Acosta, Pedro
, (2021/10/22)
A set of new dihydro-1H-pyrazolo[1,3-b]pyridine and pyrazolo[1,3-b]pyridine embelin derivatives was synthesized through a multicomponent reaction from natural embelin, 3-substituted-5-aminopyrazoles and aldehydes. The synthesized compounds were evaluated against three hematologic tumor cell lines, HEL (acute erythroid leukemia), K-562 (chronic myeloid leukemia) and HL-60 (acute myeloid leukemia), and five breast cancer cell lines (SKBR3, MCF-7, MDA-MB-231, BT-549, HS-578T). The primate non-malignant kidney Vero cell line was used as the control of cytotoxicity. From the obtained results, some structure–activity relationships were out-lined. Furthermore, in silico prediction of physicochemical properties and ADME parameters were determined for the derivatives with the best antiproliferative values.
Deadly KCN and pricey metal free track for accessing β-ketonitriles employing mild reaction conditions
Sharma, Pawan K.,Kumar, Rajiv,Ram, Sita,Chandak, Navneet
supporting information, p. 1847 - 1856 (2021/04/26)
A one pot synthesis of β-ketonitriles from readily accessible 3-chloropropenals using economically benign iodine, aqueous ammonia and sodium hydroxide solution, employing mild reaction conditions have been described. This report presents a convenient, inexpensive, highly toxic-matter-free and eco-friendly approach for β-ketonitriles.
Selective Synthesis of β-Ketonitriles via Catalytic Carbopalladation of Dinitriles
Zeng, Ge,Liu, Jichao,Shao, Yinlin,Zhang, Fangjun,Chen, Zhongyan,Lv, Ningning,Chen, Jiuxi,Li, Renhao
, p. 861 - 867 (2021/01/09)
A practical, convenient, and highly selective method of synthesizing β-ketonitriles from the Pd-catalyzed addition of organoboron reagents to dinitriles has been developed. This method provides excellent functional-group tolerance, a broad scope of substrates, and the convenience of using commercially available substrates. The method is expected to show further utility in future synthetic procedures.
Method for synthesizing beta-ketonitrile and derivatives thereof
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Paragraph 0056-0060, (2021/04/21)
The invention discloses a method for synthesizing beta-ketonitrile and derivatives thereof. The beta-ketonitrile is prepared by a reaction of malononitrile and derivatives thereof with arylboronic acid. According to the invention, reactants are wide in source and low in cost; the reaction is carried out in a solvent, and the solvent is a mixture of toluene and water; in the process of the reaction, a palladium catalyst, an acid additive and a ligand are also added into the solvent; the acidic additive is any one selected from benzenesulfonic acid, p-toluenesulfonic acid, p-nitrobenzenesulfonic acid, trifluoromethanesulfonic acid and trifluoroformic acid; and the ligand is any one selected from 4,4'-dimethyl-2,2'-bipyridyl, 6,6'-dimethyl-2,2'-bipyridyl and 5,5'-dimethyl-2,2'-bipyridyl. The method in the invention can directly synthesize the target product in one step, does not need to separate an intermediate product, can obtain the target product only by a stirring reaction under normal pressure, has the highest yield of 98%, is especially suitable for synthesis of beta-ketonitrile derivatives sensitive to alkaline conditions, and provides better guarantee for development of organic compounds related to beta-ketonitrile derivatives.
Structure guided design of potent indole-based ATX inhibitors bearing hydrazone moiety with tumor suppression effects
Guo, Ming,Jia, Fang,Jiang, Nan,Lei, Hongrui,Li, Changtao,Yang, Yu,Zhai, Xin,Zhu, Minglin
, (2020/06/21)
ATX was capable of catalyzing the hydrolysis of LPC to the lipid mediator LPA which attracted considerable attention on the development of potent ATX inhibitors. Herein, driven by the HTS product indole-based lead 1, a hybridization strategy was utilized to construct the trifluoroacetyl hydrazone moiety through assembling the phenyl thiazole fragment to the indole skeleton of lead 1. After a systematic structure guided optimization, by cycling the phenyl thiazole to the compacted benzothiazole or decreasing the lipophilicity, two promising ATX inhibitors (9j and 25a) were identified with IC50 values of 2.1 nM and 19.0 nM, respectively. All compounds were tested a panel of cancer cell lines and a preliminary affinity on breast cancer cell lines (SI > 16.5) were observed which shed a light on their potential application of breast cancer relevant cases. Through a dedicated docking study, the intramolecular pseudo-ring within the trifluoroacetylhydrazone moiety played a significant role in constraining the binding poses of 9j and 25a. Finally, a binding free energy calculation was conducted to examine the contribution of different interactions in binding affinity.
Hydrogen Bond Directed Photocatalytic Hydrodefluorination and Methods of Use Thereof
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, (2021/01/22)
Methods of synthesizing compounds comprising fluorinated aryl groups are disclosed, wherein said methods utilize hydrogen bond directed photocatalytic hydrodefluorination.
Synthesis and refining method of 4-fluorobenzoyl acetonitrile
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Paragraph 0025; 0026, (2020/06/20)
The invention relates to a synthesis and refining method of 4-fluorobenzoyl acetonitrile, which comprises the following steps: dissolving malononitrile in a solvent, and adding fluorobenzene and trifluoromethanesulfonic acid to react, thereby obtaining a 4-fluorobenzoyl acetonitrile crude product; adding an alcohol and a small molecular alkane into the 4-fluorobenzoyl acetonitrile crude product for recrystallizationso as to obtain 4-fluorobenzoyl acetonitrile. The method has the advantages of short synthesis steps, safety and simplicity in operation, high conversion rate and low cost, anda basis is provided for development and application of 4-fluorobenzoyl acetonitrile.
Synthesis and Structure-Activity Relationship of Dual-Stage Antimalarial Pyrazolo[3,4- b]pyridines
Eagon, Scott,Hammill, Jared T.,Sigal, Martina,Ahn, Kevin J.,Tryhorn, Julia E.,Koch, Grant,Belanger, Briana,Chaplan, Cory A.,Loop, Lauren,Kashtanova, Anna S.,Yniguez, Kenya,Lazaro, Horacio,Wilkinson, Steven P.,Rice, Amy L.,Falade, Mofolusho O.,Takahashi, Rei,Kim, Katie,Cheung, Ashley,Dibernardo, Celine,Kimball, Joshua J.,Winzeler, Elizabeth A.,Eribez, Korina,Mittal, Nimisha,Gamo, Francisco-Javier,Crespo, Benigno,Churchyard, Alisje,García-Barbazán, Irene,Baum, Jake,Anderson, Marc O.,Laleu, Beno?t,Guy, R. Kiplin
, p. 11902 - 11919 (2020/11/26)
Malaria remains one of the most deadly infectious diseases, causing hundreds of thousands of deaths each year, primarily in young children and pregnant mothers. Here, we report the discovery and derivatization of a series of pyrazolo[3,4-b]pyridines targeting Plasmodium falciparum, the deadliest species of the malaria parasite. Hit compounds in this series display sub-micromolar in vitro activity against the intraerythrocytic stage of the parasite as well as little to no toxicity against the human fibroblast BJ and liver HepG2 cell lines. In addition, our hit compounds show good activity against the liver stage of the parasite but little activity against the gametocyte stage. Parasitological profiles, including rate of killing, docking, and molecular dynamics studies, suggest that our compounds may target the Qo binding site of cytochrome bc1.
