141644-91-9Relevant academic research and scientific papers
Concise total synthesis of antiarrhythmic drug dronedarone via a conjugate addition followed intramolecular heck cyclization
Madhasu, Madhu,Doda, Sai Reddy,Begari, Prem Kumar,Dasari, Krishna Rao,Thalari, Gangadhar,Kadari, Sudhakar,Yadav, Jhillu Singh
, p. 1861 - 1866 (2021/07/09)
A concise, scalable, and an efficient total synthesis for dronedarone (2) was described using conjugate addition followed by intramolecular Heck cyclization. The other key reaction includes selective reduction of nitro functionality and addition of lithiated terminal alkyne to the aldehyde. The overall yield of this approach is 44% in six steps.
Discovery of dronedarone and its analogues as NLRP3 inflammasome inhibitors with potent anti-inflammation activity
Chen, Hao,Chen, Xiuhui,Sun, Ping,Wu, Dan,Yue, Hu,Pan, Jintao,Li, Xinxuan,Zhang, Cheng,Wu, Xinyi,Hua, Lei,Hu, Wenhui,Yang, Zhongjin
supporting information, (2021/06/18)
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.
Benzofuran compound and application thereof
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Paragraph 0053-0055; 0068-0069, (2021/08/06)
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.
Efficient Syntheses of Diverse, Medicinally Relevant Targets Planned by Computer and Executed in the Laboratory
Klucznik, Tomasz,Mikulak-Klucznik, Barbara,McCormack, Michael P.,Lima, Heather,Szymku?, Sara,Bhowmick, Manishabrata,Molga, Karol,Zhou, Yubai,Rickershauser, Lindsey,Gajewska, Ewa P.,Toutchkine, Alexei,Dittwald, Piotr,Startek, Micha? P.,Kirkovits, Gregory J.,Roszak, Rafa?,Adamski, Ariel,Sieredzińska, Bianka,Mrksich, Milan,Trice, Sarah L.J.,Grzybowski, Bartosz A.
supporting information, p. 522 - 532 (2018/03/21)
The Chematica program was used to autonomously design synthetic pathways to eight structurally diverse targets, including seven commercially valuable bioactive substances and one natural product. All of these computer-planned routes were successfully executed in the laboratory and offer significant yield improvements and cost savings over previous approaches, provide alternatives to patented routes, or produce targets that were not synthesized previously. Although computers have demonstrated the ability to challenge humans in various games of strategy, their use in the automated planning of organic syntheses remains unprecedented. As a result of the impact that such a tool could have on the synthetic community, the past half century has seen numerous attempts to create in silico chemical intelligence. However, there has not been a successful demonstration of a synthetic route designed by machine and then executed in the laboratory. Here, we describe an experiment where the software program Chematica designed syntheses leading to eight commercially valuable and/or medicinally relevant targets; in each case tested, Chematica significantly improved on previous approaches or identified efficient routes to targets for which previous synthetic attempts had failed. These results indicate that now and in the future, chemists can finally benefit from having an “in silico colleague” that constantly learns, never forgets, and will never retire. Multistep synthetic routes to eight structurally diverse and medicinally relevant targets were planned autonomously by the Chematica computer program, which combines expert chemical knowledge with network-search and artificial-intelligence algorithms. All of the proposed syntheses were successfully executed in the laboratory and offer substantial yield improvements and cost savings over previous approaches or provide the first documented route to a given target. These results provide the long-awaited validation of a computer program in practically relevant synthetic design.
2-butyl-3 - (4-substituted propoxy benzoyl) - 5-substituted aminobenzofuran preparation method
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Paragraph 0085-0087, (2017/01/23)
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.
Preparation method of dronedarone hydrochloride key intermediate
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Paragraph 0022; 0031-0033, (2016/10/08)
The invention relates to a preparation method of a dronedarone hydrochloride key intermediate. The preparation method comprises following steps: 1) 2-butyl-benzofuran-5-ylamine hydrochloride and phthalic anhydride are subjected to reflux reaction under alkaline conditions so as to protect amino groups; and 2) 4-[3-(dibutyl amino) propoxy] benzoic acid is added into Eaton's reagent for stirring reaction, an intermediate 1 is added, temperature is controlled for reaction, a free amine is obtained via treatment, and the free amine and oxalic acid are subjected to salt forming reaction so as to obtain compound IV 5-amino-2-n-butyl-3-[4-(3-n-dibutyl aminopropoxy) benzoyl]benzofuran oxalate. The dronedarone hydrochloride key intermediate is prepared by taking 2-butyl-benzofuran-5-ylamine hydrochloride as the starting raw material; production of the dronedarone free amino is high in selectivity, and high in yield; fewer steps are needed; so that the preparation method is suitable for industrialized production.
METHOD FOR PREPARING 5-AMINO-BENZOFURAN DERIVATIVES
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Paragraph 0036; 0037; 0038; 0039; 0040, (2015/02/19)
The invention relates to a method for preparing 5-amino-benzoyl-benzofuran derivatives having the general formula in which R1 is hydrogen or an alkyl or aryl group and R2 is hydrogen, an alkyl, alkoxy or dialkylaminoalkoxy group. Acc
PROCESS FOR PREPARING AMINOBENZOYLBENZOFURAN DERIVATIVES
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Paragraph 0041; 0042, (2013/07/05)
The disclosure relates to a process for preparing 5-aminobenzoylbenzofuran derivatives of formula I: in which R1 and R2 are as defined in the disclosure; by reduction of a 5-nitrobenzofuran derivative of formula II: using a hydrogen
An improved and efficient process for the production of dronedarone hydrochloride, an antiarrhythmia drug
Mali, Anil C.,Ippar, Sharad S.,Bodke, Mahendra B.,Patil, Nilesh S.,Mathad, Vijayavitthal T.
, p. 863 - 868 (2013/07/28)
An improved, high-yielding, and efficient process for the production of dronedarone hydrochloride (1), a class III antiarrhythmia drug for the prevention of cardiac arrhythmias such as atrial fibrillation (AF) is described. The developed process avoids isolation of unstable intermediates at several stages by telescoping the steps upon individual optimization, thereby minimizing the turnaround time of the batch cycle and increasing the throughput. Potential impurities (byproducts) arise during the reaction at various stages, and carry-over impurities from starting materials were controlled selectively by designing reaction conditions and suitable workup procedures, resulting in an increased overall yield from 33% (as per processes reported in the literature) to 66%.
Synthesis of dronedarone and salts thereof
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Page/Page column 10, (2012/03/27)
The present invention relates to a process for preparation of Dronedarone or pharmaceutically acceptable salts thereof. More particularly, the present invention provides a process for preparation of Dronedarone hydrochloride, without the isolation of Dronedarone base.
