444325-84-2Relevant academic research and scientific papers
Novel Human Urate Transporter 1 Inhibitors as Hypouricemic Drug Candidates with Favorable Druggability
Zhao, Tong,Meng, Qing,Sun, Zhuosen,Chen, Yanyu,Ai, Wei,Zhao, Zean,Kang, Dongwei,Dong, Yue,Liang, Ruipeng,Wu, Ting,Pang, Jianxin,Liu, Xinyong,Zhan, Peng
, p. 10829 - 10854 (2020)
Lesinurad, a human urate transporter 1 (URAT1) inhibitor approved as a medication for the treatment of hyperuricemia associated with gout in 2015, can cause liver and renal toxicity. Here, we modified all three structural components of lesinurad by applying scaffold hopping, bioisosterism, and substituent-decorating strategies. In a mouse model of acute hyperuricemia, 21 of the synthesized compounds showed increased serum uric acid (SUA)-reducing activity; SUA was about 4-fold lower in animals treated with 44, 54, and 83 compared with lesinurad or benzbromarone. In the URAT1 inhibition assay, 44 was over 8-fold more potent than lesinurad (IC50: 1.57 μM vs 13.21 μM). Notably, 83 also displayed potent inhibitory activity (IC50 = 31.73 μM) against GLUT9. Furthermore, we also preliminarily explored the effect of chirality on the potency of the promising derivatives 44 and 54. Compounds 44, 54, and 83 showed favorable drug-like pharmacokinetics and appear to be promising candidates for the treatment of hyperuricemia and gout.
The Chameleonic Nature of Platinum(II) Imidazopyridine Complexes
Pinter, Piermaria,Pittkowski, Rebecca,Soellner, Johannes,Strassner, Thomas
, p. 14173 - 14176 (2017/10/07)
The synthesis and characterization of cyclometalated C^C* platinum(II) complexes with unique photophysical properties, aggregation induced enhancement of the quantum yields with a simultaneous decrease of phosphorescence lifetimes, is reported. Additional
Imidazopyridine thioglycolic acid derivative and preparation method and application thereof
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, (2017/01/02)
The invention relates to an imidazopyridine thioglycolic acid derivative and a preparation method and application thereof. The compound has the structure as shown in a formula I or a formula II or a formula III. The invention further relates to a preparation method of the compound with the structure as shown in the formula I or the formula II or the formula III and pharmaceutical compositions. The invention further provides application of the compound in preparation of drugs for resisting gout. Please see the formula in the description.
Discovery and characterization of novel imidazopyridine derivative CHEQ-2 as a potent CDC25 inhibitor and promising anticancer drug candidate
Song, Yu'Ning,Lin, Xiaoqian,Kang, Dongwei,Li, Xiao,Zhan, Peng,Liu, Xinyong,Zhang, Qingzhu
, p. 293 - 307 (2014/06/24)
Cell division cycle (CDC) 25 proteins are key phosphatases regulating cell cycle transition and proliferation via the interactions with CDK/Cyclin complexes. Overexpression of CDC25 proteins is frequently observed in cancer and is related to aggressiveness, high-grade tumors and poor prognosis. Thus, inhibiting CDC25 activity in cancer treatment appears a good therapeutic strategy. In this article, refinement of the initial hit XDW-1 by synthesis and screening of a focused compound library led to the identification of a novel set of imidazopyridine derivatives as potent CDC25 inhibitors. Among them, the most potent molecule was CHEQ-2, which could efficiently inhibit the activities of CDC25A/B enzymes as well as the proliferation of various different types of cancer cell lines in vitro assay. Moreover, CHEQ-2 triggered S-phase cell cycle arrest in MCF-7, HepG2 and HT-29 cell lines, accompanied by generation of ROS, mitochondrial dysfunction and apoptosis. Besides, oral administration of CHEQ-2 (10 mg/kg) significantly inhibited xenografted human liver tumor growth in nude mice, while demonstrated extremely low toxicity (LD50 > 2000 mg/kg). These findings make CHEQ-2 a good starting point for further investigation and structure modification.
Arylazolyl(azinyl)thioacetanilides. Part 10: Design, synthesis and biological evaluation of novel substituted imidazopyridinylthioacetanilides as potent HIV-1 inhibitors
Li, Xiao,Zhan, Peng,Liu, Hong,Li, Dongyue,Wang, Liu,Chen, Xuwang,Liu, Huiqing,Pannecouque, Christophe,Balzarini, Jan,Clercq, Erik De,Liu, Xinyong
, p. 5527 - 5536 (2012/10/29)
In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with novel structures, we have employed a scaffold hopping strategy to explore the chemically diversed space of bioactive compounds. The original arylazolylthioacetanilide platform
An orally active corticotropin releasing factor 1 receptor antagonist from 8-aryl-1,3a,7,8-tetraaza-cyclopenta[a]indenes
Han, Xiaojun,Civiello, Rita,Pin, Sokhom S.,Burris, Kevin,Balanda, Lynn A.,Knipe, Jay,Ren, Shelly,Fiedler, Tracey,Browman, Kaitlin E.,Macci, Robert,Taber, Matthew T.,Zhang, Jie,Dubowchik, Gene M.
, p. 2026 - 2030 (2007/10/03)
8-Aryl-1,3a,7,8-tetraaza-cyclopenta[a]indenes represent a novel series of high-affinity corticotropin-releasing factor-1 receptor (CRF1R) antagonists. Herein we report the synthesis and SAR around the tricyclic core and the anxiolytic activity of an orall
