90537-40-9Relevant articles and documents
Discovery of novel high potent and cellular active ADC type PTP1B inhibitors with selectivity over TC-PTP via modification interacting with C site
Du, Yongli,Zhang, Yanhui,Ling, Hao,Li, Qunyi,Shen, Jingkang
, p. 692 - 700 (2018)
PTP1B serving as a key negative regulator of insulin signaling is a novel target for type 2 diabetes and obesity. Modification at ring B of N-{4-[(3-Phenyl-ureido)-methyl]-phenyl}-methane-sulfonamide template to interact with residues Arg47 and Lys41 in t
The discovery of novel, potent ERR-alpha inverse agonists for the treatment of triple negative breast cancer
Du, Yongli,Song, Lianhua,Zhang, Liudi,Ling, Hao,Zhang, Yanhui,Chen, Haifei,Qi, Huijie,Shi, Xiaojin,Li, Qunyi
, p. 457 - 467 (2017/05/19)
The estrogen-related receptor α (ERRα) is an orphan receptor and a novel target for solid tumor therapy, conceivably through effects on the regulation of tumor cell energy metabolism associated with energy stress within solid tumor micro environments. Here we describe the discovery of novel potent inverse agonists of ERRα. In?vitro, compound 11 potently inhibits ERRα’s transcriptional activity by preventing endogenous PGC-1α and ERRα binding and suppresses the proliferation of different human cancer cell lines and the migration of breast cancer cells (MDA-MB-231). In?vivo, compound 11 demonstrates a strong inhibitory effect on the growth of human breast cancer xenografts (MDA-MB-231) and the tumor growth is inhibited by 40.9% after treating with compound 11 (30?mg/kg). The binding mode shows that compound 11 interacts with the binding pocket of ERRα through hydrogen interactions with the residue Gly397 and hydrophobic interactions with the hydrophobic residues. All these results suggest that compound 11 represents a novel potent ERRα inverse agonist and is promising in the discovery of antitumor compounds for the treatment of triple negative breast cancer.
Novel urea protein tyrosine phosphatase 1B inhibitor, and preparation method, pharmaceutical composition and application thereof
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, (2017/01/09)
The invention relates to novel urea compounds with a structure as shown in a general formula I in the specification or pharmaceutically acceptable salts thereof, wherein the urea compounds and the pharmaceutically acceptable salts thereof can be used as a novel inhibitor of protein tyrosine phosphatase (PTP) 1B. The invention also relates to a pharmaceutical composition containing the compounds as shown in the general formula I or the pharmaceutically acceptable salts of the compounds. The compounds as shown in the general formula I or the pharmaceutically acceptable salts thereof have the effect of inhibiting the activity of the protein tyrosine phosphatase 1B (PTP1B), and can be applied in preparation of drugs capable of preventing and/or treating symptoms or diseases like hyperglycemia and type 2 diabetes.
5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-methyl-benzamide new compound and preparation method and application thereof
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, (2017/05/05)
The invention provides a new compound. The name of the compound is 5-[3-(2,5-diethoxy-4-methylsulfonyl-benzyl)-ureido]-2-ethoxy-N-methyl-benzamide; molecular weight of the compound is 508.5; and structure of the compound is as shown in the structural formula (compound 1). Meanwhile, the invention provides a preparation method of the compound 1. The compound provided by the invention has good drug-likeness and can be used in the research field of new drugs, especially in the research field of type-II diabetes innovative drugs.
Design and Synthesis of Novel Cyclooxygenase-1 Inhibitors as Analgesics: 5-Amino-2-ethoxy-N-(substituted-phenyl)benzamides
Fukai, Ryosuke,Zheng, Xiaoxia,Motoshima, Kazunori,Tai, Akihiro,Yazama, Futoshi,Kakuta, Hiroki
, p. 550 - 560 (2011/12/22)
We previously found that N-(4-aminophenyl)-4-trifluoromethylbenzamide (TFAP), a COX-1 inhibitor, exhibits an analgesic effect without causing gastric damage. Unfortunately, TFAP causes reddish purple coloration of urine, and its analgesic effect is less potent than that of indomethacin. Herein we describe our study focusing on the development of 4- and 5-amino-2-alkoxy-N-phenylbenzamide scaffolds, designed on the basis of the structures of TFAP and parsalmide, another known COX-1 inhibitory analgesic agent. 5-Amino-2-ethoxy-N-(2- or 3-substituted phenyl)benzamide derivatives exhibited analgesic activity in a murine acetic acid induced writhing test. Among these compounds, 5-amino-2-ethoxy-N-(2-methoxyphenyl)benzamide (9v) possesses potent COX-1 inhibitory and analgesic activities, similar to those of indomethacin. In addition, 5-amino-2-ethoxy-N-(3-trifluoromethylphenyl)benzamide (9g) showed a more potent analgesic effect than indomethacin or 9v without causing apparent gastric damage or coloration of urine, although its COX-1 inhibitory activity was weaker than that of indomethacin or 9v. Thus, 9g and 9v appear to be promising candidates for analgesic agents and are attractive lead compounds for further development of COX-1 inhibitors.
