- Discovery of dronedarone and its analogues as NLRP3 inflammasome inhibitors with potent anti-inflammation activity
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Inhibiting NLRP3 inflammasome activation is a prospective therapeutic strategy for uncontrolled inflammatory diseases. It is the first time that dronedarone, a multiply ion channel blocker, was identified as a NLRP3-inflammasome inhibitor with an IC50 value of 6.84 μM against IL-1β release. A series of novel 5-amide benzofuran derivatives were designed and synthesized as NLRP3-inflammasome inhibitors. Compound 8c showed slightly increased activity (IC50 = 3.85 μM) against IL-1β release. Notably, treatment with 8c could significantly inhibit NLRP3-mediated IL-1β release and ameliorate peritoneal inflammation in a mouse model of sepsis. Collectively, 8c is a promising lead compound for further chemical development as a NLRP3 inhibitor with anti-inflammation effects.
- Chen, Hao,Chen, Xiuhui,Sun, Ping,Wu, Dan,Yue, Hu,Pan, Jintao,Li, Xinxuan,Zhang, Cheng,Wu, Xinyi,Hua, Lei,Hu, Wenhui,Yang, Zhongjin
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- Benzofuran compound and application thereof
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The invention provides a benzofuran compound as shown in a formula (I) or pharmaceutically acceptable salt thereof, and application thereof. The compound can selectively inhibit activation of NLRP3 inflammasomes and inhibit maturation and secretion of inflammation activation signal molecules Caspase-1 and P20 and inflammatory cytokines IL-1beta, has a good prevention and treatment effect on NLRP3 inflammasome related diseases, and particularly has a remarkable prevention and treatment effect on peritonitis and gouty arthritis. Therefore, the compound can be used for preparing drugs for treating NLRP3 inflammasome-related diseases, such as anti-inflammatory drugs or auxiliary anti-inflammatory drugs.
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- 2-butyl-3 - (4-substituted propoxy benzoyl) - 5-substituted aminobenzofuran and its application
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The invention discloses 2-n-butyl-3-(4-subsitituted propylbenzoyl)-5-substituted amino benzofuran and application thereof. The 2-n-butyl-3-(4-subsitituted propylbenzoyl)-5-substituted amino benzofuran can be used for preparing dronedarone and pharmaceutic
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- 2-butyl-3 - (4-substituted propoxy benzoyl) - 5-substituted aminobenzofuran preparation method
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The invention discloses a method for preparing 2-n-butyl-3-(4-substituted-propoxybenzoyl)-5-substituted aminobenzofuran, which comprises the steps of: dissolving a compound shown as a formula (III) into a solvent, adding a compound shown as a formula (V) into the obtained solution, reacting under the catalysis of a Lewis acid, and then collecting the 2-n-butyl-3-(4-substituted-propoxybenzoyl)-5-substituted aminobenzofuran (IV) from a reaction product. The method not only ensures that chemical structures of adopted raw materials and intermediates are all different, but also avoids using expensive metal catalysts and reaction conditions of high-pressure hydrogenation, greatly reduces the preparation cost for 2-n-butyl-3-(4-(3-di-n-butylaminopropoxy)benzoyl)-5-aminobenzofuran, is more suitable for industrialized mass preparation, and is higher in positive progress effect and actual application value, and apparent in competitive advantages compared with a reported literature method. A reaction formula is as follows.
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- PROCESS FOR PREPARING AMINOBENZOFURAN DERIVATIVES
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This disclosure relates to a process for preparing 5-aminobenzofuran derivatives of general formula (I): in which R1 and R2 are as defined in the description, by treating a 5-N-alkylamidobenzofuran derivative of general formula (II): in which R1, R2, and R3 are as defined in the description, with a strong acid, so as to form an acid addition salt of the compound of formula (I), which salt is itself treated, if necessary, with a basic agent so as to form this compound of formula (I) in free base form.
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