17745-04-9Relevant articles and documents
Structure-based discovery of potent and selective small-molecule inhibitors targeting signal transducer and activator of transcription 3 (STAT3)
Huang, Qiuyao,Zhong, Yan,Li, Bingbing,Ouyang, Shumin,Deng, Lin,Mo, Jianshan,Shi, Shuo,Lv, Nan,Wu, Ruibo,Liu, Peiqing,Hu, Wenhao,Zhang, Xiaolei,Wang, Yuanxiang
, (2021/05/17)
STAT3 has been validated as an attractive anticancer target due to its important roles in cancer initiation and progression. However, discovery of potent and selective STAT3 small-molecule inhibitors with druglike properties is still challenging. In this study, two series of substituted 2-phenylquinolines and 2-arylimidazo[1,2-a]pyridines were designed through structure-based drug discovery approach by condensing the privileged structures of STX-119 and SH4-54. Our study has resulted in the discovery of a number of highly potent and selective STAT3 inhibitors, exemplified by compound 39 with the privileged structure of 2-phenylimidazo[1,2-a]pyridine, which selectively inhibits phosphorylation of STAT3 and suppresses subsequent signaling pathway. Moreover, 39 inhibits cell growth, migration and invasion of human triple negative breast cancer (TNBC) cells lines. Consistently, it achieves significant and dose-dependent tumor growth inhibition in both cell line-derived and patient-derived xenograft tumor models in mice. These results clearly indicate that 39 is a highly potent and selective STAT3 inhibitor.
Preparation method of minodronic acid intermediate
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Paragraph 0087-0094, (2020/04/17)
The invention relates to a preparation method of a minodronic acid intermediate. The method comprises the following steps: reacting a compound I-1 raw material with a compound I-2 under the action ofa catalyst cuprous bromide and an acid-binding agent potassium tert-butoxide to obtain an intermediate I-3, hydrolyzing the intermediate I-3 by sodium hydroxide to obtain an intermediate 1-4, and decarboxylating the intermediate 1-4 by cuprous oxide to obtain an intermediate I, namely the minodronic acid intermediate. Compared with the prior art, the method has the advantages of easily available raw material, simple process, convenience in operation, high reaction yield (the three-step yield is as high as 80%), and facilitation of industrial production.
Minodronic acid intermediate synthesis system and synthesis process thereof
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Paragraph 0020; 0046-0081, (2018/11/03)
The invention discloses a minodronic acid intermediate synthesis system and a synthesis process thereof. The synthesis system comprises an agitating tank and a reaction kettle, the agitating tank comprises a rack, a mixing tank, and agitating assemblies, each agitating assembly comprises an agitating motor, an agitating shaft, agitating blades, and impellers, and a heater is arranged on the external wall of the mixing tank; the reaction kettle comprises a barrel, a feed inlet, a discharge outlet, a support, and a reaction kettle agitator; and the agitating tank is located upon the reaction kettle. The invention further discloses a preparation method of minodronate intermediate 2-(imidazo[1,2-a]pyridine-3-yl)acetate, which comprises the following steps: imidazo[1,2-a]pyridine and oxalyl chloride as starting materials undergo Friedel-Crafts acylation and Huang Ming-long reduction, and thereby the intermediate 2-(imidazo[1,2-a]pyridine-3-yl)acetate is obtained. According to the invention,environmental pollution is reduced, the reaction step is shortened, the whole reaction process is simplified, the preparation of 2-(imidazo[1,2-a]pyridine-3-yl)acetate is easy to control, the reaction conditions are mild, post-treatment is simple, and industrial production is easy.
