1204-70-2Relevant academic research and scientific papers
Towards New Tricyclic Motifs: Intramolecular C–H Arylation as the Key Step in a Formal [3+3] Cyclocondensation Strategy
Vrijdag, Johannes L.,De Ruysscher, Dries,De Borggraeve, Wim M.
, p. 1465 - 1474 (2017)
Tricyclic scaffolds structurally related to the well-known benzodiazepine class of drugs show diverse biological activities strikingly different from those of their benzodiazepine counterparts. Interested by this scaffold-hopping perspective, we previousl
Synthesis and bioactivity of phenyl substituted furan and oxazole carboxylic acid derivatives as potential PDE4 inhibitors
Lin, Yinuo,Ahmed, Wasim,He, Min,Xiang, Xuwen,Tang, Riyuan,Cui, Zi-Ning
, (2020/10/02)
In this present study, a series of 5-phenyl-2-furan and 4-phenyl-2-oxazole derivatives were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. In vitro results showed that the synthesized compounds exhibited considerable inhibitory ac
Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis
Liu, Mingming,Liang, Yuru,Zhu, Zhongzhen,Wang, Jin,Cheng, Xingxing,Cheng, Jiayi,Xu, Binpeng,Li, Rong,Liu, Xinhua,Wang, Yang
, p. 9299 - 9314 (2019/10/16)
In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure-activity relationships step by step, compound 30m was discovered as the most active inhibitor (IC50 = 0.32 μM) with no obvious cytotoxicity (CC50 > 50 μM). It effectively attenuated hypoxia-induced HIF-1α protein accumulation and reduced transcription of vascular epidermal growth factor in a dose-dependent manner, which was further demonstrated by its inhibitory potency on capillary-like tube formation, angiogenesis of zebrafish as well as cellular migration and invasion. Importantly, compound 30m exhibited antimetastatic potency in breast cancer lung metastasis in the mice model, indicating its promising therapeutic potential for prevention and treatment of tumor metastasis. These results definitely merit attention for further rational design of more efficient HIF-1 inhibitors in the future.
Design, synthesis and biological evaluation of 2,4-disubstituted oxazole derivatives as potential PDE4 inhibitors
Li, Ya-Sheng,Hu, De-Kun,Zhao, Dong-Sheng,Liu, Xing-Yu,Jin, Hong-Wei,Song, Gao-Peng,Cui, Zi-Ning,Zhang, Lian-Hui
, p. 1852 - 1859 (2017/03/08)
In this study, a series of pyrazole derivatives containing 4-phenyl-2-oxazole moiety were designed and synthesized in a concise way, some of which exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNF-α release. Compound
Rh(III)-catalyzed cyclization reaction of azoles with alkynes: Efficient synthesis of azole-fused-pyridines
Chen, Xuebing,Wu, Youzhi,Xu, Jinyi,Yao, Hequan,Lin, Aijun,Huang, Yue
supporting information, p. 9186 - 9189 (2015/09/07)
A Rh(III)-catalyzed cyclization of azoles with alkynes has been developed. A variety of azole-fused-pyridines were obtained in good to excellent yields and regioselectivity. Both the C5 and the C4 position of azoles were suitable for the reaction.
Tertiary amides with a five-membered heteroaromatic ring as new probes for the translocator protein
Cosimelli, Barbara,Simorini, Francesca,Taliani, Sabrina,La Motta, Concettina,Da Settimo, Federico,Severi, Elda,Greco, Giovanni,Novellino, Ettore,Costa, Barbara,Da Pozzo, Eleonora,Bendinelli, Sara,Martini, Claudia
scheme or table, p. 4506 - 4520 (2011/11/05)
In this study novel ligands of the translocator protein (TSPO), characterized by a five-membered aromatic heterocycle (i.e. oxazole, isoxazole, oxadiazole), a phenyl ring, and an amide side chain of carboxy or acetic type, were designed using a previously
N -((1-benzyl-1 H -1,2,3-triazol-4-yl)methyl)arylamide as a new scaffold that provides rapid access to antimicrotubule agents: Synthesis and evaluation of antiproliferative activity against select cancer cell lines
Stefely, Jonathan A.,Palchaudhuri, Rahul,Miller, Patricia A.,Peterson, Rebecca J.,Moraski, Garrett C.,Hergenrother, Paul J.,Miller, Marvin J.
supporting information; experimental part, p. 3389 - 3395 (2010/09/04)
A series of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamides was synthesized by copper-catalyzed azide-alkyne cycloaddition (CuAAC) and afforded inhibitors of cancer cell growth. For example, compound 13e had an IC 50 of 46 nM against MCF-7 human breast tumor cells. Structure-activity relationship (SAR) studies demonstrated that (i) meta-phenoxy substitution of the N-1-benzyl group is important for antiproliferative activity and (ii) a variety of heterocyclic substitutions for the aryl group of the arylamide are tolerated. In silico COMPARE analysis of antiproliferative activity against the NCI-60 human tumor cell line panel revealed a correlation to clinically useful antimicrotubule agents such as paclitaxel and vincristine. This in silico correlation was supported by (i) in vitro inhibition of tubulin polymerization, (ii) G2/M-phase arrest in HeLa cells as assessed by flow cytometry, and (iii) perturbation of normal microtubule activity in HeLa cells as observed by confocal microscopy. The results demonstrate that N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide is a readily accessible small molecule scaffold for compounds that inhibit tubulin polymerization and tumor cell growth.
Five-membered heterocyclic ureas suitable for the donor-donor-acceptor hydrogen-bonding modules
Hisamatsu, Yosuke,Fukumi, Yuki,Shirai, Naohiro,Ikeda, Shin-ichi,Odashima, Kazunori
, p. 2005 - 2009 (2008/09/19)
Five-membered heterocyclic ureas are capable of forming the unfolded conformer without preorganization by using the intramolecular hydrogen bond, and are suitable for the DDA hydrogen-bonding modules. In contrast, six-membered heterocyclic ureas are desta
Preparation of novel antibacterial agents. Replacement of the central aromatic ring with heterocycles
Li, Jianke,Wakefield, Brian D.,Ruble, J. Craig,Stiff, Cory M.,Romero, Donna L.,Marotti, Keith R.,Sweeney, Michael T.,Zurenko, Gary E.,Rohrer, Douglas C.,Thorarensen, Atli
, p. 2347 - 2350 (2008/12/21)
Discovery of novel antibacterial agents is a significant challenge. We have recently reported on our discovery of novel antibacterial agents in which we have rapidly optimized potency utilizing a parallel chemistry approach. These advanced leads suffer from high affinity for human serum albumin (HSA). In an effort to decrease the affinity for HSA we have prepared a series of heterocyclic analogs, which retained antibacterial activity and demonstrated reduced affinity for HSA.
