75717-53-2Relevant articles and documents
Discovery of Novel Polycyclic Heterocyclic Derivatives from Evodiamine for the Potential Treatment of Triple-Negative Breast Cancer
Chen, Zhe-Sheng,Li, Dahong,Qiu, Yangyi,Wu, Liang,Xu, Jinyi,Xu, Shengtao,Yang, Dong-Hua,Yao, Hong,Zhou, Manzhen
supporting information, p. 17346 - 17365 (2021/12/09)
Evodiamine (Evo) is a quinazolinocarboline alkaloid found in Evodia rutaecarpa and exhibits moderate antiproliferative activity. Herein, we report using a scaffold-hopping approach to identify a series of novel polycyclic heterocyclic derivatives based on Evo as the topoisomerase I (Top1) inhibitor for the treatment of triple-negative breast cancer (TNBC), which is an aggressive subtype of breast cancer with limited treatment options. The most potent compound 7f inhibited cell growth in a human breast carcinoma cell line (MDA-MB-231) with an IC50 value of 0.36 μM. Further studies revealed that Top1 was the target of 7f, which directly induced irreversible Top1-DNA covalent complex formation or induced an oxidative DNA lesion through an indirect mechanism mediated by reactive oxygen species. More importantly, in vivo studies showed that 7f exhibited potent antitumor activity in a TNBC-patient-derived tumor xenograft model. These results suggest that compound 7f deserves further investigation as a promising candidate for the treatment of TNBC.
Novel evodiamine derivatives as well as preparation method and application of novel evodiamine derivatives
-
Paragraph 0098; 0101, (2018/03/13)
The invention relates to the field of medicinal chemistry and particularly relates to novel evodiamine derivatives and also discloses a preparation method of the novel evodiamine derivatives and an application of the novel evodiamine derivatives to treatm
Discovery of benzofuran-3(2H)-one derivatives as novel DRAK2 inhibitors that protect islet β-cells from apoptosis
Wang, Sheng,Xu, Lei,Lu, Yu-Ting,Liu, Yu-Fei,Han, Bing,Liu, Ting,Tang, Jie,Li, Jia,Wu, Jiangping,Li, Jing-Ya,Yu, Li-Fang,Yang, Fan
, p. 195 - 208 (2017/03/02)
Death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2) is a serine/threonine kinase that plays a key role in a wide variety of cell death signaling pathways. Inhibition of DRAK2 was found to efficiently protect islet β-cells from apoptosis and hence DRAK2 inhibitors represent a promising therapeutic strategy for the treatment of diabetes. Only very few chemical entities targeting DRAK2 are currently known. We carried out a high throughput screening and identified compound 4 as a moderate DRAK2 inhibitor with an IC50value of 3.15?μM. Subsequent SAR studies of hit compound 4 led to the development of novel benzofuran-3(2H)-one series of DRAK2 inhibitors with improved potency and favorable selectivity profiles against 26 selected kinases. Importantly, most potent compounds 40 (IC50?=?0.33?μM) and 41 (IC50?=?0.25?μM) were found to protect islet β-cells from apoptosis in dose-dependent manners. These data support the notion that small molecule inhibitors of DRAK2 represents a promising strategy for the treatment of diabetes.
NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS
-
Page/Page column 96, (2015/07/07)
Novel tricyclic compounds of Formula (I) and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.
NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS FOR THE TREATMENT OF OSTEOPOROSIS
-
Page/Page column 95, (2015/07/07)
Novel tricyclic compounds of the formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.
Design, synthesis and discovery of 5-hydroxyaurone derivatives as growth inhibitors against HUVEC and some cancer cell lines
Cheng, Huimin,Zhang, Lianwen,Liu, Yingxue,Chen, Shaopeng,Cheng, Hao,Lu, Xin,Zheng, Zhuxia,Zhou, Guo-Chun
experimental part, p. 5950 - 5957 (2011/01/12)
A series of 4′-substituted 5-hydroxyaurone derivatives were synthesized and their inhibitory activities against the proliferation of endothelial cells and two cancer cell lines were studied. Some of these compounds functioned as potent inhibitors against the proliferation of endothelial cells and cancer cells but possessed much weaker cytotoxic activities against non-cancer cell line of CCC-HPF-1. It was demonstrated that two most active compounds 16 and 27 effectively inhibited in vitro endothelial cell motility and tube formation, which are basic properties of endothelial cells for angiogenesis. Moreover, 16 and 27 also showed significant activities against in vitro cancer cell invasion, indicating that they have potential to inhibit cancer metastasis. These composite results suggest that 4′-substituted 5-hydroxyaurone is indeed a candidate structural scaffold for anticancer agent targeting activated endothelial cells and fast-proliferating cancer cells.
Asymmetric [4 + 3] cycloadditions between benzofuranyldiazoacetates and dienes: Formal synthesis of (+)-frondosin B
Olson, Jeremy P.,Davies, Huw M. L.
, p. 573 - 576 (2008/04/12)
The reaction of benzofuranyldiazoacetates with 1,3-dienes catalyzed by the dirhodium tetracarboxylate Rh2(R-DOSP)4, generates formal [4 + 3] cycloadducts with >94% de and 91-98% ee. The reaction proceeds by a tandem cyclopropanation/
6,7,8,9-SUBSTITUTED 1-PHENYL-1,5-DIHYDRO-PYRIDO[3,2-B]INDOL-2-ONES USEFUL AS ANTI-INFECTIVE PHARMACEUTICAL AGENTS
-
Page/Page column 78-79, (2008/06/13)
This invention concerns the compounds (I); the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein X is NR2, O, S, SO, SO2; R1 is hydrogen, cyano, halo, substituted carbonyl, methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; n is 1, 2 or 3; R2 is hydrogen, aryl substituted with a radical -COOR4; or R2 is substituted C1-10alkyl,C2-10alkenyl or C3-7cycloalkyl; or R2 is a radical of formula: (b-1); (b-2); -CpH2p-CH(OR14)-CqH2q-R15 (b-3); -CH2-CH2-(O-CH2-CH2)m-OR14 (b-4); -CH2-CH2-(O-CH2-CH2)m-NR5aR5b (b-5); -a1=a2-a3=a4- is -CH=CH-CH=CH- ; -N=CH-CH=CH- ;-CH=N-CH=CH- ; -CH=CH- N=CH- ; -CH=CH-CH=N- (c-5); wherein one of the hydrogen atoms in (c-1) - (c-5) is replaced by particular radicals; R3 is nitro, cyano, amino, halo, hydroxy, C1-4alkyloxy, hydroxycarbonyl, substituted carbonyl, methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, N-hydroxy- methanimidamidyl or Het1.
Antioxidant-Based Inhibitors of Leukotriene Biosynthesis. The Discovery of 6--1-propen-3-yl>-2,3-dihydro-5-benzofuranol, a Potent Topical Antiinflammatory Agent
Hammond, Milton L.,Zambias, Robert A.,Chang, Michael N.,Jensen, Norman P.,McDonald, John,et al.
, p. 909 - 918 (2007/10/02)
The leukotrienes, metabolites of arachidonic acid produced through the action of the enzyme 5-lipoxygenase, are important mediators of immediate hypersensitivity and inflammation.Among the variety of diseases in which the leukotrienes may play a symptomat
