63430-79-5Relevant academic research and scientific papers
Inhibition of zika virus infection by fused tricyclic derivatives of 1,2,4,5-tetrahydroimidazo[1,5-a]quinolin-3(3aH)-one
Lee, Emily M.,Medina, Angelica,Sun, Xia,Tang, Hengli,Wang, Decai,Xu, Bin,Zhou, Guo-Chun
, (2020)
Zika virus (ZIKV) infection represents a significant threat to the global health system, and the search for efficient antivirals to ZIKV remains necessary and urgent. In this study, we extended the exploration of our previously discovered scaffold of 1H-pyrrolo[1,2-c]imidazol-1-one and revealed that two trans isomers of compounds 2 and 7 and one mixture with major trans isomer of compound 3 as novel tetrahydroquinoline-fused imidazolone derivatives are active against ZIKV infection but they are not virucidal. Western Blot and ELISA analyses of ZIKV NS5 and NS1 further demonstrate that compounds of (±)-2, (±)-3 and (±)-7 act as effective agents against ZIKV infection. We show that the N10′s basicity is not the basic requirement for these compounds’ antiviral activity in the current work. Importantly, tuning of some pharmacophores including substituents at arene can generate promising candidates for anti-ZIKV agents.
Design, synthesis and biological evaluation of novel thiohydantoin derivatives as potent androgen receptor antagonists for the treatment of prostate cancer
Wang, Ao,Wang, Yawan,Meng, Xin,Yang, Yushe
, (2021/01/07)
Prostate cancer (PC) is the most common malignancy in men worldwide. Here, two series of novel thiohydantoin derivatives of enzalutamide as potent androgen receptor (AR) antagonists were designed and synthesized. Among them, compound 31c was identified as an AR antagonist which is 2.3–fold more potent than enzalutamide. Molecular docking studies were performed to explain the improved potency of 31c at AR. In cell proliferation assays, 31c exhibited similar anti-proliferative activities with enzalutamide against hormone sensitive LNCaP cells and AR-overexpressing LNCaP/AR cells. These data indicate that 31c can be a good lead compound for further structure optimization for the treatment of prostate cancer.
Tuning the Catalytic Performance of Cobalt Nanoparticles by Tungsten Doping for Efficient and Selective Hydrogenation of Quinolines under Mild Conditions
Concepción, Patricia,Corma, Avelino,Liu, Lichen,Puche, Marta,Sorribes, Iván
, p. 8197 - 8210 (2021/07/13)
Non-noble bimetallic CoW nanoparticles (NPs) partially embedded in a carbon matrix (CoW@C) have been prepared by a facile hydrothermal carbon-coating methodology followed by pyrolysis under an inert atmosphere. The bimetallic NPs, constituted by a multishell core-shell structure with a metallic Co core, a W-enriched shell involving Co7W6 alloyed structures, and small WO3 patches partially covering the surface of these NPs, have been established as excellent catalysts for the selective hydrogenation of quinolines to their corresponding 1,2,3,4-tetrahydroquinolines under mild conditions of pressure and temperature. It has been found that this bimetallic catalyst displays superior catalytic performance toward the formation of the target products than the monometallic Co@C, which can be attributed to the presence of the CoW alloyed structures.
Palladium supported on magnesium hydroxyl fluoride: An effective acid catalyst for the hydrogenation of imines and N-heterocycles
Agbossou-Niedercorn, Francine,Corre, Yann,Dongare, Mohan K.,Kemnitz, Erhard,Kokane, Reshma,Michon, Christophe,Umbarkar, Shubhangi B.
supporting information, p. 19572 - 19583 (2021/11/04)
Palladium catalysts supported on acidic fluorinated magnesium hydroxide Pd/MgF2-x(OH)x were prepared through precipitation or impregnation methods. Applications to the hydrogenation of various aldimines and ketimines resulted in good catalytic activities at mild temperatures using one atmosphere of hydrogen. Quinolines, pyridines and other N-heterocycles were successfully hydrogenated at higher temperature and hydrogen pressure using low palladium loadings and without the use of any acid additive. Such reactivity trend confirmed the positive effect of the Br?nsted and Lewis acid sites from the fluorinated magnesium hydroxide support resulting in the effective pre-activation of N-heterocycle substrates and therefore in the good catalytic activity of the palladium nanoparticles during the hydrogenations. As demonstrated in the hydrogenation of imines, the catalyst was recycled up to 10 times without either loss of activity or palladium leaching. This journal is
Enantioselective Synthesis of 2-Functionalized Tetrahydroquinolines through Biomimetic Reduction
Zhao, Zi-Biao,Wang, Jie,Zhu, Zhou-Hao,Chen, Mu-Wang,Zhou, Yong-Gui
supporting information, p. 9112 - 9117 (2021/11/24)
Biomimetic asymmetric reduction of 2-functionalized quinolines has been successfully developed with the chiral and regenerable NAD(P)H model CYNAM in the presence of transfer catalyst simple achiral phosphoric acids, providing the chiral 2-functionalized
Multikilogram Synthesis of a Potent Dual Bcl-2/Bcl-xL Antagonist. 1. Manufacture of the Acid Moiety and Development of Some Key Reactions
Hardouin, Christophe,Baillard, Sandrine,Barière, Fran?ois,Copin, Chloé,Craquelin, Anthony,Janvier, Solenn,Lemaitre, Sylvain,Le Roux, Stéphane,Russo, Olivier,Samson, Sébastien
, p. 652 - 669 (2019/12/24)
Our efforts toward the process development of drug candidate 1 are described in a series of two papers. This manuscript focuses on the synthesis of kilogram quantities of acid precursor 2 to provide batches of material for preclinical studies and first-in
Boric acid catalyzed chemoselective reduction of quinolines
Adhikari, Priyanka,Bhattacharyya, Dipanjan,Das, Animesh,Konwar, Monuranjan,Nandi, Sekhar,Sarmah, Bikash Kumar
supporting information, p. 1214 - 1220 (2020/02/22)
Boric acid promoted transfer hydrogenation of substituted quinolines to synthetically versatile 1,2,3,4-tetrahydroquinolines (1,2,3,4-THQs) was described under mild reaction conditions using a Hantzsch ester as a mild organic hydrogen source. This methodology is practical and efficient, where isolated yields are excellent and reducible functional groups are well tolerated in the N-heteroarene moiety. The reaction parameters and tentative mechanistic pathways are demonstrated by various control experiments and NMR studies. The present work can also be scaled up to obtain gram quantities and the utility of the developed process is illustrated by the transformation of 1,2,3,4-THQs into a series of biologically important molecules including the antiarrhythmic drug nicainoprol.
Discovery of pyridine tetrahydroisoquinoline thiohydantoin derivatives with low blood-brain barrier penetration as the androgen receptor antagonists
Bian, Jinlei,Chen, Xijing,Du, Qianming,Ge, Raoling,Li, Yan,Li, Zhiyu,Lu, Xiaoyu,Meng, Ying,Wang, Jubo,Wu, Hongxi,Xu, Xi,Xue, Siqi,Yang, Yong,Zhao, Zhili
, (2020/03/11)
Prostate cancer (PC) is the most diagnosed type of malignancy in men and the major frequently cause of cancer-related death worldwide. The androgen receptor (AR) has become a promising drug target for the treatment of PC. Here, we reported the design, optimization and evaluation of pyridine tetrahydroisoquinoline thiohydantoin derivatives with improved activity and safety as potent AR antagonists. The most promising compound 42f exhibited potent inhibitory activity on AR and strongly blocked AR nuclear translocation. Moreover, 42f displayed promising in vitro antitumor activity toward AR-dependent prostate cancer cell lines (LNCaP) and also demonstrated therapeutic effects in LNCaP xenograft tumor model in mice (TGI: 79%) with no apparent toxicity observed in vivo. More importantly, 42f showed negligible penetration of the brain-blood barrier (BBB) compared with enzalutamide. These results provide a foundation for the development of a new class of androgen receptor antagonists for potential therapeutics against PC with lower seizurogenic risk for patients.
Cyclic formyl and cyclic ketone compounds as well as preparation method and pharmaceutical application thereof
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Paragraph 0035; 0061-0062, (2020/08/27)
The invention discloses cyclic formyl and cyclic ketone compounds as well as a preparation method and a pharmaceutical application thereof. The compound shown in (I) has a good function of inhibitinginfection and replication of Zika viruses and dengue vir
Nanolayered Cobalt-Molybdenum Sulfides as Highly Chemo- and Regioselective Catalysts for the Hydrogenation of Quinoline Derivatives
Sorribes, Iván,Liu, Lichen,Doménech-Carbó, Antonio,Corma, Avelino
, p. 4545 - 4557 (2018/05/22)
Herein, a general protocol for the preparation of a broad range of valuable N-heterocyclic products by hydrogenation of quinolines and related N-heteroarenes is described. Interestingly, the catalytic hydrogenation of the N-heteroarene ring is chemoselectively performed when other facile reducible functional groups, including alkenes, ketones, cyanides, carboxylic acids, esters, and amides, are present. The key to successful catalysis relies on the use of a nanolayered cobalt-molybdenum sulfide catalyst hydrothermally synthesized from earth-abundant metal precursors. This heterogeneous system displays a tunable composition of phases that allows for catalyst regeneration. Its catalytic activity depends on the composition of the mixed phase of cobalt sulfides, being higher with the presence of Co3S4, and could also be associated with the presence of transient Co-Mo-S structures that mainly vanish after the first catalytic run.
