- Medicament for treating respiratory syncytial virus infection and preparation method thereof
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The invention provides a benzothiazole compound which can be used for preparing a medicament for treating respiratory syncytial virus (RSV) infection as well as a preparation method and medical application thereof. As shown by an in-vitro pharmacological
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Paragraph 0035; 0037
(2018/09/11)
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- From Lead to Drug Candidate: Optimization of 3-(Phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine Derivatives as Agents for the Treatment of Triple Negative Breast Cancer
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Herein we report the sophisticated process of structural optimization toward a previously disclosed Src inhibitor, compound 1, which showed high potency in the treatment of triple negative breast cancer (TNBC) both in vitro and in vivo but had considerable toxicity. A series of 3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine derivatives were synthesized. In vitro cell-based phenotypic screening together with in vivo assays and structure-activity relationship (SAR) studies finally led to the discovery of N-(3-((4-amino-1-(trans-4-hydroxycyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)ethynyl)-4-methylphenyl)-4-methyl-3-(trifluoromethyl)benzamide (13an). 13an is a multikinase inhibitor, which potently inhibited Src (IC50 = 0.003 μM), KDR (IC50 = 0.032 μM), and several kinases involved in the MAPK signal transduction. This compound showed potent anti-TNBC activities both in vitro and in vivo, and good pharmacokinetic properties and low toxicity. Mechanisms of action of anti-TNBC were also investigated. Collectively, the data obtained in this study indicate that 13an could be a promising drug candidate for the treatment of TNBC and hence merits further studies.
- Zhang, Chun-Hui,Chen, Kai,Jiao, Yan,Li, Lin-Li,Li, Ya-Ping,Zhang, Rong-Jie,Zheng, Ming-Wu,Zhong, Lei,Huang, Shen-Zhen,Song, Chun-Li,Lin, Wan-Ting,Yang, Jiao,Xiang, Rong,Peng, Bing,Han, Jun-Hong,Lu, Guang-Wen,Wei, Yu-Quan,Yang, Sheng-Yong
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supporting information
p. 9788 - 9805
(2016/11/19)
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- The flocculated acryloyldimethyltauric molecule ligand
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Provided are certain benzothiazole, imidazothiazole, imidazopyrimidine and imidazopyridine compounds, including, for example: formula (I) and pharmaceutically and physiologically acceptable salts, hydrates, and solvates thereof. Such compounds can be used as diagnostic ligands or labels of tau protein and PHF.
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Paragraph 0606
(2016/10/08)
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- N -pyridyl and pyrimidine benzamides as KCNQ2/Q3 potassium channel openers for the treatment of epilepsy
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A series of N-pyridyl benzamide KCNQ2/Q3 potassium channel openers were identified and found to be active in animal models of epilepsy and pain. The best compound 12 [ICA-027243, N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide] has an EC50 of 0.38 μM and is selective for KCNQ2/Q3 channels. This compound was active in several rodent models of epilepsy and pain but upon repeated dosing had a number of unacceptable toxicities that prevented further development. On the basis of the structure-activity relationships developed around 12, a second compound, 51, [N-(2-chloro-pyrimidin-5-yl)-3,4-difluoro- benzamide, ICA-069673], was prepared and advanced into a phase 1 clinical study. Herein, we describe the structure-activity relationships that led to the identification of compound 12 and to the corresponding pyrimidine 51.
- Amato, George,Roeloffs, Rosemarie,Rigdon, Greg C.,Antonio, Brett,Mersch, Theresa,McNaughton-Smith, Grant,Wickenden, Alan D.,Fritch, Paul,Suto, Mark J.
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supporting information; experimental part
p. 481 - 484
(2011/08/22)
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- Diacyl-substituted guanidines, a process for their preparation, their use as medicine or diagnostic aid, and medicine containing them
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Diacyl-substituted guanidines of the formula I are described where X(1) and X(2) are as defined herein. The compounds are suitable for use as antiarrhythmic pharmaceuticals possessing a cardioprotective component for the prophylaxis and treatment of infar
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