- Amide compound as well as preparation method and application thereof
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The invention relates to an amide compound and a preparation method and application thereof. The amide compound has a structure as shown in a formula (I). The amide compound can induce generation of endogenous interferon in an animal body and has the potential of being developed into an antiviral drug.
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Paragraph 0093-0096
(2021/09/26)
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- Development of BET inhibitors as potential treatments for cancer: A new carboline chemotype
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We describe our efforts to introduce structural diversity to a previously described triazole-containing N1-carboline series of bromodomain and extra-terminal (BET) inhibitors. N9 carbolines were designed to retain favorable binding interactions that the N1-carbolines possess. A convergent synthetic route enabled modifications to reduce clearance, enhance physicochemical properties, and improve the overall in vitro profile. This work led to the identification of a potent BET inhibitor, (S)-2‐{8‐fluoro‐5‐[(3‐fluoropyridin‐2‐yl)(oxan‐4‐yl)methyl]‐7‐[4‐(2H3)methyl‐1‐methyl‐1H‐1,2,3‐triazol‐5‐yl]‐5H‐pyrido[3,2‐b]indol‐3‐yl}propan‐2‐ol (10), a compound with enhanced oral exposure in mice. Subsequent evaluation in a mouse triple-negative breast cancer tumor model revealed efficacy at 4 mg/kg of N9-carboline 10.
- Degnan, Andrew P.,Everlof, Gerry,Fang, Haiquan,Fanslau, Carolynn,Gavai, Ashvinikumar V.,Haarhoff, Zuzana,Hill, Matthew D.,Huang, Lisa,Kramer, Melissa,Lee, Francis,Madari, Shilpa,Marsilio, Frank,Morrison, John,Quesnelle, Claude,Sheriff, Steven,Simmermacher-Mayer, Jean,Sinz, Michael,Tokarski, John,Westhouse, Richard,Wiebesiek, Amy,Xie, Chunshan,Yan, Chunhong,Zhao, Jiuqiao,Zvyaga, Tatyana
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supporting information
(2021/09/28)
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- Computer-aided discovery of aminopyridines as novel JAK2 inhibitors
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The Janus kinase 2 (JAK2)-mediated signaling pathway plays an important role in controlling cell survival, proliferation, and differentiation. In recent years, genetic, biological, and physiological evidence has established JAK2 inhibitors as effective chemotherapeutic agents for the treatment of many different cancers. For this reason, we sought to identify novel small molecule inhibitors of JAK2. Using Surflex-Dock software, we tested 3010 compounds with known chemical structures in silico for their ability to interact with the JAK2 ATP-binding pocket. We selected the 10 highest-scoring compounds and tested their abilities to inhibit JAK2 activity in vitro. Compound 1a (ethyl 1-(5-((3-methoxyphenyl)carbamoyl)-3-nitropyridin-2-yl)piperidine-4-carboxylate) was identified. Optimization of 1a using docking studies led to the discovery of compounds 1b and 1d, potent JAK2 inhibitors. Furthermore, as V-shaped kinase inhibitors can curve around the protein backbone and access deep into the pocket, we developed a new series of compounds with a non-linear sulfonamide bond. Nine compounds were prepared and evaluated for JAK2 inhibitory effects. Compounds 7e (IC50 = 6.9 μM) and 7h (IC50 = 12.2 μM) showed better JAK2 inhibition, validating our design approach. This study successfully applied virtual screening for hit discovery, and a docking study for hit optimization. In addition, a novel approach to drug discovery, combining structure- and shape-based drug design, facilitated the design of more potent JAK2 inhibitors. The methods provide a guide for future development of inhibitors targeting JAK2 and other kinases.
- Zhao, Chao,Yang, Su Hui,Khadka, Daulat Bikram,Jin, Yifeng,Lee, Kyung-Tae,Cho, Won-Jea
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p. 985 - 995
(2015/03/04)
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- THE NITROPYRIDINYL ETHYLENEIMINE COMPOUND, THE PHARMACEUTICAL COMPOSITION CONTAINING IT, THE PREPARATION METHOD AND USE THEREOF
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The present invention discloses a nitropyridinyl ethyleneimine compound as shown in the formula I and a preparation method of the same, as well as use of the compound in manufacture of a prodrug and in manufacture of a drug for treating a tumor.
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Page/Page column 9
(2011/10/10)
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- The design of efficient and selective routes to pyridyl analogues of 3-oxo-3,4-dihydro-2H-1,4-(benzothiazine or benzoxazine)-6-carbaldehydes
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This Letter describes the synthesis of challenging pyridyl analogues of 3-oxo-3,4-dihydro-2H-1,4-(benzothiazine or benzoxazine)-6-carbaldehydes. The six different routes described are high yielding, contain no major purification issues and have been used to give gram quantities of each aldehyde.
- Brooks, Gerald,Dabbs, Steven,Davies, David T.,Hennessy, Alan J.,Jones, Graham E.,Markwell, Roger E.,Miles, Timothy J.,Owston, Nathan A.,Pearson, Neil D.,Peng, Tony W.
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scheme or table
p. 5035 - 5037
(2011/01/04)
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- 1,2,4-TRIAZOLO[4,3-A]PYRIDINES USEFUL IN THE TREATMENT OF GASTROINTESTINAL DISORDERS
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The invention provides compounds of the formula (1), in which the substituents and symbols are as defined in the description. The compounds inhibit the secretion of gastric acid.
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Page/Page column 17
(2010/02/13)
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- Compounds useful for treating hepatitis C virus
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A series of compounds of Formula I are disclosed which are useful in treating viral hepatitus C. 1
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