- Pyridazinone compound, preparation method thereof, pharmaceutical composition and application thereof
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The invention relates to a pyridazinone compound shown as a formula I or an isomer thereof, or a pharmaceutically acceptable salt, ester, a prodrug or a solvate thereof, a preparation method thereof,a pharmaceutical composition and an application of the pharmaceutical composition for preparing a dengue virus inhibitor. The pyridazinone compound has a structure shown in the formula I. The compoundor the pharmaceutical composition thereof has anti-dengue virus activity and better selectivity, and can be used for preventing and/or treating dengue virus infection.
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- Palladium-Catalyzed Acylation Reactions: A One-Pot Diversified Synthesis of Phthalazines, Phthalazinones and Benzoxazinones
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A sequential one-pot strategy for the diversified synthesis of phthalazines, phthalazinones and benzoxazinones was presented. This strategy proceeds through [Pd]-catalyzed acylation and nucleophilic cyclocondensation with dinucleophilic reagents. This process was based on direct coupling with simple bench-top aldehydes without the assistance of directing group and without activating the carbonyl group. The process is highly advantageous because it employs simple nitrogen-based nucleophiles, and non-toxic and readily accessible aldehydes as the carbonyl source. Most importantly, the strategy was applied to the one-pot synthesis of PDE-4 inhibitor.
- Suchand, Basuli,Satyanarayana, Gedu
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p. 2233 - 2246
(2018/06/04)
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- Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors
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Using a dengue replicon cell line-based screening, we identified 3-(dimethylamino)propyl(3-((4-(4-fluorophenyl)-1-oxophthalazin-2(1H)-yl)methyl)phenyl)carbamate (10a) as a potent DENV-2 inhibitor, with an IC50 value of 0.64 μM. A series of novel phthalazinone derivatives based on hit 10a were synthesized and evaluated for their in vitro anti-DENV activity and cytotoxicity. The subsequent SAR study and optimization led to the discovery of the most promising compound 14l, which displayed potent anti-DENV-2 activity, with low IC50 value against DENV-2 RNA replication of 0.13 μM and high selectivity (SI = 89.2) with acceptable pharmacokinetics profiles.
- Lu, Dong,Liu, Jianan,Zhang, Yunzhe,Liu, Feifei,Zeng, Limin,Peng, Runze,Yang, Li,Ying, Huazhou,Tang, Wei,Chen, Wuhong,Zuo, Jianping,Tong, Xiankun,Liu, Tao,Hu, Youhong
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p. 328 - 337
(2018/01/17)
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- Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-imidazolyl)alkyl]- 1(2H)-phthalazinones
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A number of 4-substituted 2-[ω-(1-imidazolyl)alkyl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane A2 synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.
- Yamaguchi,Kamei,Koga,Akima,Kuroki,Ohi
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p. 4052 - 4060
(2007/10/02)
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