117238-61-6Relevant articles and documents
Synthesis and biological evaluation of aeroplysinin analogues: a new class of receptor tyrosine kinase inhibitors
Hinterding, Klaus,Knebel, Axel,Herrlich, Peter,Waldmann, Herbert
, p. 1153 - 1162 (1998)
Receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR) and the platelet-derived growth factor receptor (PDGFR), are critically involved in the transduction of mitogenic signals across the plasma membrane and therefore in the regulation of cell growth and proliferation. Enhanced RTK activity is associated with proliferative diseases such as cancer, psoriasis and atherosclerosis, while decreased function may be associated for instance with diabetes. EGFR and PDGFR are selectively inhibited by analogues of the marine natural product aeroplysinin. The synthetic inhibitors display IC50 values in the low micromolar range and in contrast to the natural product show pronounced inhibitory activity in cultured cells in vivo. The mechanism of inhibition is likely based on a covalent modification of the target enzymes by reaction of epoxy ketone 8 with various nucleophiles. Copyright (C) 1998 Elsevier Science Ltd.
Selective inhibition of receptor tyrosine kinases by synthetic analogues of aeroplysinin
Waldmann,Hinterding,Herrlich,Rahmsdorf,Knebel
, p. 1541 - 1542 (1997)
IC50 values in the low micromolar range for the inhibition of receptor tyrosine kinases, which are critically involved in the transduction of mitogenic signals and thus in the regulation of cell growth and proliferation, are characteristic of synthetic analogues of marine natural product aeroplysinin 1 such as 2. In addition, they show pronounced inhibitory activity in cultured cells in vivo.
3-substituted coumarin derivative and application and GPR35 receptor agonist
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Paragraph 0058-0059, (2018/06/04)
The invention discloses a 3-substituted coumarin derivative and a pharmaceutically acceptable salt, a solvate, a hydrate or a crystal form. The compound of the invention generally exhibits high agonistic activity against human G protein-coupled receptor 35 (GPR35) and is specific agonists of the human GPR35 receptor. The compound provided by the invention is an active ligand of the novel GPR35 receptor, and the compound and the pharmaceutically acceptable salt, the solvate, the hydrate or the crystal form thereof generally exhibit higher activity and good selectivity to the human GPR35. The 3-substituted coumarin derivative is the specific agonist of the GPR35 receptor and can be used in the preparation of a medicament for treating, preventing and inhibiting a disease mediated by the GPR35receptor.
Discovery of 2H-Chromen-2-one Derivatives as G Protein-Coupled Receptor-35 Agonists
Wei, Lai,Wang, Jixia,Zhang, Xiuli,Wang, Ping,Zhao, Yaopeng,Li, Jiaqi,Hou, Tao,Qu, Lala,Shi, Liying,Liang, Xinmiao,Fang, Ye
, p. 362 - 372 (2017/04/26)
A family of 2H-chromen-2-one derivatives were identified as G protein-coupled receptor-35 (GPR35) agonists using dynamic mass redistribution assays in HT-29 cells. The compounds with 1H-tetrazol-5-yl in 3-substituted position displayed higher potency than the corresponding carboxyl analogs, and the hydroxyl group in the 7-position also played an important role in GPR35 agonistic activity. 6-Bromo-7-hydroxy-8-nitro-3-(1H-tetrazol-5-yl)-2H-chromen-2-one (50) was found to be the most potent GPR35 agonist with an EC50 of 5.8 nM. Calculating the physicochemical properties of compounds with moderate to high potency suggested that compounds 30, 50, and 51 showed good druggability. This study provides a novel series of GPR35 agonists, and compound 50 may be a powerful tool to study GPR35.
Discovery and mechanism study of SIRT1 activators that promote the deacetylation of fluorophore-labeled substrate
Wu, Jiahui,Zhang, Dengyou,Chen, Lei,Li, Jianneng,Wang, Jianling,Ning, Chengqing,Yu, Niefang,Zhao, Fei,Chen, Dongying,Chen, Xiaoyan,Chen, Kaixian,Jiang, Hualiang,Liu, Hong,Liu, Dongxiang
supporting information, p. 761 - 780 (2013/04/10)
SIRT1 is an NAD+-dependent deacetylase, whose activators have potential therapeutic applications in age-related diseases. Here we report a new class of SIRT1 activators. The activation is dependent on the fluorophore labeled to the substrate. To elucidate the activation mechanism, we solved the crystal structure of SIRT3/ac-RHKKac-AMC complex. The structure revealed that the fluorophore blocked the H-bond formation and created a cavity between the substrate and the Rossmann fold. We built the SIRT1/ac-RHKK ac-AMC complex model based on the crystal structure. Km and Kd determinations demonstrated that the fluorophore decreased the peptide binding affinity. The binding modes of SIRT1 activators indicated that a portion of the activators interacts with the fluorophore through π-stacking, while the other portion inserts into the cavity or interacts with the Rossmann fold, thus increasing the substrate affinity. Our study provides new insights into the mechanism of SIRT1 activation and may aid the design of novel SIRT1 activators.
Total syntheses of subereamollines A and B
Shearman, James W.,Myers, Rebecca M.,Brenton, James D.,Ley, Steven V.
supporting information; experimental part, p. 62 - 65 (2011/02/24)
The first total syntheses of (+)- and (-)-subereamollines A and B are reported. The enantiomeric forms of the natural products were obtained by preparative chiral HPLC separation of the corresponding racemates.
Antiangiogenic versus cytotoxic activity in analogues of aeroplysinin-1
Cordoba, Ruben,Tormo, Nelida Salvador,Medarde, Antonio Fernandez,Plumet, Joaquin
, p. 5300 - 5315 (2008/03/13)
A series of analogues of the potentially angiogenic inhibitor aeroplysinin-1 1 were synthesized and their in vitro antiangiogenic and cytotoxic activities evaluated. In the case of epoxy ketone 6 and azlactone 36 the relationship sprouting inhibition assay/cytotoxicity in BAE cells was enhanced by one order and two orders of magnitude, respectively, with respect to the reference. These results imply more specific antiangiogenic properties for the synthesized derivatives.
Electrochemical synthesis of spiroisoxazole derivatives and its application to natural products
Ogamino, Takahisa,Ishikawa, Yuichi,Nishiyama, Shigeru
, p. 73 - 78 (2007/10/03)
Efficient synthesis of the trans-spiroisoxazole (1) and its unnatural cis-isomer (2) was accomplished by employing anodic oxidation of 4, followed by Zn(BH4)2 reduction. This method was applied to an assembly of the carbon framework of zamamistatin (12).
Pyridinium hydrobromide perbromide induces ipsobromodeformylation in o-hydroxy and o-methoxy substituted aromatic aldehydes
Córdoba, Rubén,Plumet, Joaquín
, p. 9303 - 9305 (2007/10/03)
The reaction of o-hydroxy and o-methoxy substituted aromatic aldehydes with PHPB in pyridine gives aromatic bromination products including those arising from ipsobromodeformylation.
Approaches to the synthesis of some tyrosine-derived marine sponge metabolites: Synthesis of verongamine and purealidin N
Boehlow,Harburn,Spilling
, p. 3111 - 3118 (2007/10/03)
The oxidation of tyrosine ethyl ester (7) with Na2WO4/H2O2 in ethanol, dimethyldioxirane in acetone, or methyltrioxorhenium/H2O2 in EtOH gave the corresponding tyrosine oxime (8) in high yi
