cas 2257-69-4, 4-CHLORO-1,2-DIHYDROPHTHALAZIN-1-ONE

Articles about 2257-69-4Total 8 be found

Discovery of Phthalazinone Derivatives as Novel Hepatitis B Virus Capsid Inhibitors
HBV capsid assembly has been viewed as an attractive target for new antiviral therapies against HBV. On the basis of a lead compound 4r, we further investigated this target to identify novel active compounds with appropriate anti-HBV potencies and improved pharmacokinetic (PK) properties. Structure-activity relationship studies based on metabolic pathways of 4r led to the identification of a phthalazinone derivative 19f with appropriate anti-HBV potencies (IC50 = 0.014 ± 0.004 μM in vitro), which demonstrated high oral bioavailability and liver exposure. In the AAV-HBV/mouse model, administration of 19f resulted in a 2.67 log reduction of the HBV DNA viral load during a 4-week treatment with 150 mg/kg dosing twice daily.
Chen, Wuhong,Liu, Feifei,Zhao, Qiliang,Ma, Xinna,Lu, Dong,Li, Heng,Zeng, Yanping,Tong, Xiankun,Zeng, Limin,Liu, Jia,Yang, Li,Zuo, Jianping,Hu, Youhong
p. 8134 - 8145
(2020)
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4-pyridine substituted phthalazinone compound as well as preparation method, pharmaceutical composition and application thereof
The invention relates to a 4-pyridine substituted phthalazinone compound, a preparation method, a pharmaceutical composition and an application thereof, the structure of the 4-pyridine substituted phthalazinone compound is shown as a formula I, the compound of the formula I has improved pharmaceutical physicochemical properties and in-vivo pharmacokinetic properties, oral bioavailability is high,druggability is good, The compound is a non-nucleoside small-molecule HBV virus inhibitor which is novel in structure and can be orally taken.
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Paragraph 0098-0101

(2021/01/04)

Phthalazinone compound and preparation method, pharmaceutical composition and use thereof
The invention relates to a phthalazinone compound and a preparation, pharmaceutical composition and use thereof, wherein the structure of the phthalazinone compound is shown as formula one, and the compound of the formula one is targeted to a virus nuclea
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Paragraph 0106; 0108; 0109; 0110

(2019/01/23)

Pyridazinone compound, preparation method thereof, pharmaceutical composition and application thereof
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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Paragraph 0092-0094

(2019/03/15)

TOLL-LIKE RECEPTOR 8 (TLR8)-SPECIFIC ANTAGONISTS AND METHODS OF MAKING AND USES THEREOF
Toll-like receptor 8 (TLR8)-specific inhibitors and methods of using the same in individuals having an autoimmune disease or an inflammatory disorder.
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Page/Page column 52

(2019/05/22)

Discovery and optimization of phthalazinone derivatives as a new class of potent dengue virus inhibitors
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
p. 328 - 337
(2018/01/17)

Synthetic method of olaparib
The invention discloses a synthetic method of olaparib. The synthetic method comprises the following steps: with phthalhydrazide as a starting material, reacting with phosphorus oxychloride to generate 1-chloro-4-carbonylpyridazine, and further reacting with ethyl 2-fluoro-5-bromomethylbenzoate, so as to generate ethyl 2-fluoro-5-[(4-carbonyl-3,4-dihydropyridazin-1-yl)methyl]benzoate; and carryingout hydrolysis and acylation, and carrying out condensation reaction by virtue of ethyl 2-fluoro-5-[(4-carbonyl-3,4-dihydropyridazin-1-yl)methyl]benzoate and 1-(cyclopropylcarbonyl)-piperazine, so asto generate olaparib. The synthetic method has the beneficial effects that phthalhydrazide is taken as the starting material for the first time, is easily available and is environmentally friendly; by utilizing Neigishi coupling, organic metal is utilized for reaction, catecholborane with a relatively high cost is not used, and zinc powder is used, so that the production cost is lowered, and thetotal yield of the route reaches 70.2%; and the reaction route is relatively short, reaction conditions are mild, and the synthetic method is suitable for industrial production.
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Paragraph 0044; 0046; 0051; 0053; 0056; 0057; 0059

(2018/07/06)

HYDRAZONES OF PHTHALAZONES. SOME FORMAZANS AND HYDRAZIDINES
In formazans, isolated during the azo coupling of arenediazonium salts with benzylidenehydrazones of 4-chloro-1-phthalazinone, the hydrogen atom is localized at the nitrogen atom of the ring and not in the formazan fragment.These formazans and their analo
Buzykin, B. I.,Bystrykh, N. N.
p. 953 - 961
(2007/10/02)