7113-10-2Relevant articles and documents
I2/TBHP-Mediated tandem cyclization and oxidation reaction: Facile access to 2-substituted thiazoles and benzothiazoles
Liu, Li,Tan, Chen,Fan, Rong,Wang, Zihan,Du, Hongguang,Xu, Kun,Tan, Jiajing
supporting information, p. 252 - 256 (2019/01/10)
The efficient synthesis of 2-substituted thiazoles and benzothiazoles has been accomplished employing readily available cysteine esters and 2-aminobenzenethiols as N and S sources. The reaction proceeds under an I2/TBHP system and involves a on
Discovery of 2-phenylthiazole-4-carboxylic acid, a novel and potent scaffold as xanthine oxidase inhibitors
Xu, Xue,Deng, Liming,Nie, Lu,Chen, Yueming,Liu, Yanzhi,Xie, Rongrong,Li, Zheng
supporting information, p. 525 - 528 (2019/01/09)
The xanthine oxidase (XO) plays an important role in producing uric acid, and therefore XO inhibitors are considered as one of the promising therapies for hyperuricemia and gout. We have previously reported a series of XO inhibitors with pyrazole scaffold to extend the chemical space of current XO inhibitors. Herein, we describe further structural optimization to explore the optimal heterocycle by replacing the thiazole ring of Febuxostat with 5 heterocycle scaffolds unexplored in this field. All of these efforts resulted in the identification of compound 8, a potent XO inhibitor (IC50 = 48.6 nM) with novel 2-phenylthiazole-4-carboxylic acid scaffold. Moreover, lead compound 8 exhibited hypouricemic effect in potassium oxonate-hypoxanthine-induced hyperuricemic mice. These results promote the understanding of ligand-receptor interaction and might help to design more promising XO inhibitors.
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.
Aryl thiazole-tryptamine marine red tide algae algicide and preparation method and application thereof
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, (2019/10/01)
The invention relates to aryl thiazole-tryptamine marine red tide algae algicide and a preparation method and application thereof. Aromatic carboxylic acid serves as an initial raw material, and synthesis of an aryl thiazole-tryptamine compound can be com
Purple acid phosphatase inhibitors as leads for osteoporosis chemotherapeutics
Hussein, Waleed M.,Feder, Daniel,Schenk, Gerhard,Guddat, Luke W.,McGeary, Ross P.
, p. 462 - 479 (2018/08/21)
Purple acid phosphatases (PAPs) are metalloenzymes that catalyse the hydrolysis of phosphate esters under acidic conditions. Their active site contains a Fe(III)Fe(II) metal centre in mammals and a Fe(III)Zn(II) or Fe(III)Mn(II) metal centre in plants. In humans, elevated PAP levels in serum strongly correlate with the progression of osteoporosis and metabolic bone malignancies, which make PAP a target suitable for the development of chemotherapeutics to combat bone ailments. Due to difficulties in obtaining the human enzyme, the corresponding enzymes from red kidney bean and pig have been used previously to develop specific PAP inhibitors. Here, existing lead compounds were further elaborated to create a series of inhibitors with Ki values as low as ～30 μM. The inhibition constants of these compounds were of comparable magnitude for pig and red kidney bean PAPs, indicating that relevant binding interactions are conserved. The crystal structure of red kidney bean PAP in complex with the most potent inhibitor in this series, compound 4f, was solved to 2.40 ? resolution. This inhibitor coordinates directly to the binuclear metal centre in the active site as expected based on its competitive mode of inhibition. Docking simulations predict that this compound binds to human PAP in a similar mode. This study presents the first example of a PAP structure in complex with an inhibitor that is of relevance to the development of anti-osteoporotic chemotherapeutics.
FIVE-MEMBERED HETEROCYCLIC AMIDES WNT PATHWAY INHIBITOR
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Paragraph 0143-0145, (2018/10/19)
The present invention discloses a five-membered heterocyclic amide WNT pathway inhibitor, which belongs to a compound that regulates the activity of a Wnt signaling pathway, and provides a method for preparing such a compound, and the use of such a compound in preparing a medicament that antagonizes the Wnt signaling pathway. The five-membered heterocyclic amide WNT pathway inhibitor provided by the invention has a remarkable anti-tumor activity based on a target-based rational drug design of, and can be used for the development of a new generation of Wnt pathway inhibitors, and has a great clinical application value and considerable market potential.
Design, synthesis and evaluation of aromatic heterocyclic derivatives as potent antifungal agents
Zhao, Shizhen,Zhang, Xiangqian,Wei, Peng,Su, Xin,Zhao, Liyu,Wu, Mengya,Hao, Chenzhou,Liu, Chunchi,Zhao, Dongmei,Cheng, Maosheng
, p. 96 - 107 (2017/05/31)
To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (1), a series of aromatic heterocyclic derivatives were designed, synthesized and evaluated for in vitro antifungal activity. Many of the target compounds showed good inhibitory activity against Candida albicans and Cryptococcus neoformans. In particular, the isoxazole nuclei were more suited for improving the activity against Aspergillus spp. Among these compounds, 2-F substituted analogues 23g and 23h displayed the most remarkable in vitro activity against Candida spp., C. neoformans, A. fumigatus and fluconazole-resistant C.alb. strains, which is superior or comparable to the activity of the reference drugs fluconazole and voriconazole. Notably, the compounds 23g and 23h exhibited low inhibition profiles for various isoforms of human cytochrome P450 and excellent blood plasma stability.
Synthesis and Biological Investigation of Oxazole Hydroxamates as Highly Selective Histone Deacetylase 6 (HDAC6) Inhibitors
Senger, Johanna,Melesina, Jelena,Marek, Martin,Romier, Christophe,Oehme, Ina,Witt, Olaf,Sippl, Wolfgang,Jung, Manfred
supporting information, p. 1545 - 1555 (2016/03/08)
Histone deacetylase 6 (HDAC6) catalyzes the removal of an acetyl group from lysine residues of several non-histone proteins. Here we report the preparation of thiazole-, oxazole-, and oxadiazole-containing biarylhydroxamic acids by a short synthetic proce
IMIDAZOTHIADIAZOLE AND IMIDAZOPYRAZINE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION
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Paragraph 00217, (2013/11/18)
The present invention provides thiazole compounds of Formula I wherein W, Y, R0, R2, R4, R5, R6, R7, X1, X2, X3 and X4 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments for treating or preventing thromboembolic disorders.
Development and characterization of new inhibitors of the human and mouse hematopoietic prostaglandin D2 synthases
Christ, Angelika N.,Labzin, Larisa,Bourne, Gregory T.,Fukunishi, Hirotada,Weber, Jane E.,Sweet, Matthew J.,Smythe, Mark L.,Flanagan, Jack U.
supporting information; experimental part, p. 5536 - 5548 (2010/11/17)
The hematopoietic prostaglandin D2 synthase has a proinflammatory effect in a range of diseases, including allergic asthma, where its product prostaglandin D2 (PGD2) has a role in regulating many of the hallmark disease characteristics. Here we describe the development and characterization of a novel series of hematopoietic prostaglandin D2 synthase inhibitors with potency similar to that of known inhibitors. Compounds N-benzhydryl-5-(3-hydroxyphenyl)thiophene-2- carboxamide (compound 8) and N-(1-amino-1-oxo-3-phenylpropan-2-yl)-6-(thiophen- 2-yl)nicotinamide (compound 34) demonstrated low micromolar potency in the inhibition of the purified enzyme, while only 34 reduced Toll-like receptor (TLR) inducible PGD2 production in both mouse primary bone marrow-derived macrophages and the human megakaryocytic cell line MEG-01S. Importantly, 34 demonstrated a greater selectivity for inhibition of PGD 2 synthesis versus other eicosanoids that lie downstream of PGH 2 (PGE2 and markers of prostacyclin (6-keto PGF 1?) and thromboxane (TXB2)) when compared to the known inhibitors HQL-79 (compound 1) and 2-phenyl-5-(1H-pyrazol-3-yl)thiazole (compound 2). Compound 34 therefore represents a selective hematopoietic prostaglandin D2 synthase inhibitor.
