57341-09-0Relevant articles and documents
MULTICYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
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Page/Page column 84; 85, (2019/05/22)
The present invention provides compounds of Formula (I), or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
ALKENE COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
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Page/Page column 70, (2019/05/22)
The present invention provides compounds of Formula (I): Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of famesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
SPIROCYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
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Paragraph 0895-0896, (2019/05/15)
The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of famesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
Design, synthesis and anti-platelet aggregation activity study of ginkgolide-1,2,3-triazole derivatives
Cui, Jian,Hu, Lean,Shi, Wei,Cui, Guozhen,Zhang, Xumu,Zhang, Qing-Wen
, (2019/06/19)
Ginkgolides are the major active component of Ginkgo biloba for inhibition of platelet activating factor receptor. An azide-alkyne Huisgen cycloaddition reaction was used to introduce a triazole nucleus into the target ginkgolide molecules. A series of ginkgolide-1,2,3-triazole conjugates with varied functional groups including benzyl, phenyl and heterocycle moieties was thus synthesized. Many of the designed derivatives showed potent antiplatelet aggregation activities with IC50 values of 5~21 nM.
HORMONE RECEPTOR MODULATORS FOR TREATING METABOLIC MUTAGENIC AND FIBROTIC CONDITIONS AND DISORDERS
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Page/Page column 187-188, (2019/04/11)
The invention relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): wherein L1, A, X1
Leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry. Part II
Cao, Jiangying,Zang, Jie,Kong, Xiujie,Zhao, Chunlong,Chen, Ting,Ran, Yingying,Dong, Hang,Xu, Wenfang,Zhang, Yingjie
, p. 978 - 990 (2019/02/09)
Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC50 value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model.
Staudinger reaction using 2,6-dichlorophenyl azide derivatives for robust aza-ylide formation applicable to bioconjugation in living cells
Meguro, Tomohiro,Terashima, Norikazu,Ito, Harumi,Koike, Yuka,Kii, Isao,Yoshida, Suguru,Hosoya, Takamitsu
supporting information, p. 7904 - 7907 (2018/07/25)
Efficient formation of water- and air-stable aza-ylides has been achieved using the Staudinger reaction between electron-deficient aromatic azides such as 2,6-dichlorophenyl azide and triarylphosphines. The reaction proceeds rapidly and has been successfully applied to chemical modification of proteins in living cells.
Alkyne-azide cycloaddition analogues of dehydrozingerone as potential anti-prostate cancer inhibitors: Via the PI3K/Akt/NF-kB pathway
Kumar, Chetan,Rasool, Reyaz Ur,Iqra, Zainab,Nalli, Yedukondalu,Dutt, Prabhu,Satti, Naresh K.,Sharma, Neha,Gandhi, Sumit G.,Goswami, Anindya,Ali, Asif
, p. 2115 - 2124 (2017/11/22)
Herein, we report the isolation and synthetic modification of dehydrozingerone (DHZ, 1), a secondary metabolite present in the rhizome of Zingiber officinale. We synthesized O-propargylated dehydrozingerone, which was subsequently coupled by alkyne-azide cycloaddition (3-20) using click chemistry. The compounds (1-20) were evaluated for their in vitro cytotoxic activity in a panel of three cancer cell lines. Among all the DHZ derivatives, 3, 6, 7, 8, 9 and 15 displayed potent cytotoxic potential with an IC50 value ranging from 1.8-3.0 μM in MCF-7, PC-3 and HCT-116 cell lines. Furthermore, compound 7 has proven to be the most potent cytotoxic compound in all the three distinct cancer cell lines and also demonstrated significant anti-invasive potential in prostate cancer. The mechanistic study of compound 7 showed that it not only suppressed the AKT/mTOR signalling which regulates nuclear transcription factor-NF-kB but also augmented the expression of anti-invasive markers E-cadherin and TIMP. Compound 7 significantly decreased the expression of pro-invasive markers vimentin, MMP-2 and MMP-9, respectively. This study underscores an efficient synthetic approach employed to evaluate the structure-activity relationship of dehydrozingerone (1) in search of potential new anticancer agents.
Discovery of a novel 6,7-disubstituted-4-(2-fluorophenoxy)quinolines bearing 1,2,3-triazole-4-carboxamide moiety as potent c-Met kinase inhibitors
Liu, Mingmei,Hou, Yunlei,Yin, Weile,Zhou, Shunguang,Qian, Ping,Guo, Zhuang,Xu, Liying,Zhao, Yangfang
, p. 96 - 108 (2016/05/24)
A series of 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety were designed, synthesized and evaluated for their in vitro cytotoxic activities against four typical cancer cell lines (A549, H460, HT-29, and MKN-45). Most compounds showed moderate-to-excellent antiproliferative activity. Compounds 32, 36, 37, 45, 51, and 52 were further examined for their inhibitory activity against c-Met kinase. The promising compound 37, with a c-Met IC50 value of 2.27 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor. The analysis of their structure-activity relationships indicated that compounds with EWGs, especially chloro group, at 2-position on the phenyl ring (moiety B) have potent antitumor activity.