- 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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Paragraph 0053-0057; 0064-0065; 0108-0109
(2021/08/06)
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- Preparation method of amiodarone hydrochloride
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The invention relates to a preparation method of amiodarone hydrochloride. According to the preparation method, synthesis of intermediate 2-butylbenzofuran is realized under effect of a catalyst, a cocatalyst, and an acid binding agent, through Sonogashira coupling cyclization reaction of 2-iodo phenol and 1-acetylene in an organic solvent at a 2-iodo phenol to 1-acetylene molar ratio of 1:09-1.3,wherein reaction temperature ranges from 30 to 60 DEG C, and reaction time ranges from 12 to 38h. Compared with the prior art, the advantages are that: operation is simplified; operation convenienceand product stability are improved; controlling of the ratio of the catalyst to the materials is capable of increasing the purities and yields of intermediates; no column chromatography purifying is needed; cost is reduced; production efficiency is increased at the same time; and convenience is provided for industrial large scale production.
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- Lewis Acid-Catalyzed Synthesis of Benzofurans and 4,5,6,7-Tetrahydrobenzofurans from Acrolein Dimer and 1,3-Dicarbonyl Compounds
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2,3-Disubstituted benzofurans were synthesized from acrolein dimer and 1,3-dicarbonyl compounds by using N-bromosuccinimide as an oxidizing agent. The method was used to synthesize two commercial drug molecules, benzbromarone and amiodarone. The proposed mechanism of the reaction involves a N-bromosuccinimide (NBS)-assisted autotandem catalysis with Lewis acid catalyst. To proof the proposed mechanism, an intermediate was isolated successfully, which can be converted to 4,5,6,7-tetrahydrobenzofurans.
- Huang, Wenbo,Xu, Jing,Liu, Changhui,Chen, Zhiyan,Gu, Yanlong
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p. 2941 - 2950
(2019/02/26)
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- Preparation method of amiodarone hydrochloride intermittent
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The invention belongs to the field of medicine synthesis, and relates to a preparation method of an amiodarone hydrochloride intermittent. The method is characterized by including the following stepsthat 1, under an alkaline condition, in the presence of a phase transfer catalyst, a compound 1 and a compound 2 are subjected to nucleophilic substitution reaction to obtain a compound 3; 2, under analkaline condition, the compound 3 is hydrolyzed to generate a compound 4; 3, the compound 4 is subjected to intramolecular aldol condensation, decarboxylation and dehydration to obtain a compound 5;4, a compound 6 and thionyl chloride are subjected to heating reaction to obtain a compound 7; 5, under the presence of lewis acid, the compound 5 and the compound 7 are subjected to friede-crafts acylation reaction to obtain a compound 8; 6, under the presence of lewis acid, the compound 8 is subjected to demethylation to generate a compound 9, namely the amiodarone hydrochloride intermittent 2-butyl-3-(4-hydroxybenzoyl)benzofuran. The preparation method of the amiodarone hydrochloride intermittent has the advantages of being short in reaction time, high in product purity and high in yield,and the amiodarone hydrochloride intermittent is suitable for large-scale industrial production.
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Paragraph 0019; 0055; 0061; 0064; 0070; 0079; 0081
(2019/01/13)
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- Synthesis method of 2-butyl-3-(4-hydroxybenzoyl) benzofuran
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The invention discloses a synthesis method of 2-butyl-3-(4-hydroxybenzoyl) benzofuran. The synthesis method comprises the following steps: performing Friedel-Crafts acylation on 2-butylbenzofuran usedas a main raw material and p-anisoyl chloride, and directly demethylating a product in reaction fluid at the end of the Friedel-Crafts reaction without separation, thus obtaining the 2-butyl-3-(4-hydroxybenzoyl) benzofuran. The operation is simplified, and a relatively small amount of wastewater is produced. The reaction process is the 'one-pot method'; and two steps of reaction are completed byone step, so that the middle operation is eliminated, and discharging of waste water, waste gas and waste residues is reduced. According to the synthesis method, the Friedel-Crafts reaction and the hydrolysis reaction are completed by only one lewis acid, so that the number of material varieties is reduced, and the operation efficiency is improved. No prohibited chemical such as phosgene is used in the synthesis method; no carbon disulfide is used either, so as to avoid odor; air is not required to be purified, so that the production cost is reduced; and in a word, the synthesis method disclosed by the invention has the following characteristics of mild reaction conditions, simple technological operation, environmental friendliness, low cost and high yield.
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Paragraph 0035-0038; 0039-0042; 0043-0046; 0047-0050
(2018/09/12)
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- A 2 - butyl - 3 - (4 - hydroxy benzoyl) benzofuran preparation method (by machine translation)
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The invention discloses a 2 - butyl - 3 - (4 - hydroxy benzoyl) benzofuran of the preparation method, the preparation method comprises the following steps: (1) the 1 - (4 - methoxyphenyl) - 1, 3 - heptyl diketone, acrolein dimer, halogenated reagent and acid catalyst in organic solvent for 25 - 100 °C stirring reaction for 1 - 8 hours, to obtain the 2 - butyl - 3 - (4 - anisoyl) benzofuran; (2) the 2 - butyl - 3 - (4 - anisoyl) benzofuran is dispersed in the organic solvent containing the acid catalyst used in the 0 - 100 °C stirring for 1 - 8 hours, to obtain the 2 - butyl - 3 - (4 - hydroxy benzoyl) benzofuran. The invention through the key process for the preparation of the overall process, and each reaction step of optimizing the parameter condition and the like, with the traditional 2 - butyl - 3 - (4 - hydroxy benzoyl) benzofuran existing synthesis method, with a route good economic performance, high reaction selectivity, industrial application value is large and the like. (by machine translation)
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Paragraph 0028; 0034; 0040; 0046-0047; 0052
(2017/09/01)
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- Amiodarone hydrochloride preparation method
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The invention belongs to the field of medicine, and especially relates to an amiodarone hydrochloride preparation method. The method takes 2-hydroxybenzaldehyde and 2-alkyl halohexoic acid ester as the raw materials to prepare 2-butylbenzofuran, 2-butylbenzofuran is taken as the raw material, and is subjected to the steps of friedel-crafts acylation, demethylation, iodination, etherification and salt forming to obtain the amiodarone hydrochloride. By employing the method, the raw materials have the advantages of low cost and easy acquisition, the process is simple, and 2-butylbenzofuran and amiodarone hydrochloride with high purity and high yield can be obtained, the cost is low, the waste water is little, and the method is suitable for industrial production.
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- DEVELOPING POTENT URATE TRANSPORTER INHIBITORS: COMPOUNDS DESIGNED FOR THEIR URICOSURIC ACTION
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A compound represented by the general Formula (I): a pharmaceutically acceptable salt or ester thereof, a solvate thereof, a chelate thereof, a non-covalent complex thereof, a pro-drug thereof, a deuterated radio-labeled analog thereof, and mixtures of any of the foregoing, wherein: A - K are individually selected from carbon or nitrogen; X = -O, -NR1,or -S; R1-11 are individually selected from the group consisting of-H, C1-C6 alkyl, C6-C aryl, substituted C6-C14 aryl, C1-C14-alkoxy, halogen, hydroxyl, carboxy, cyano, C1-C6-alkanoyloxy, C1-C6-alkylthio, C1-C6-alkylsulfonyl, trifluoromethyl, hydroxy, C2-C6-alkoxycarbonyl, C2-C6-alkanoylamino, -O-R12, S-R12,-SO2-Ri2, -NHSO2R12 and -NHCO2R12, wherein R12 is phenyl, naphthyl, or phenyl or naphthly substituted with one to three groups selected from C1-C6-alkyl, C6-C10 aryl,C1-C6-alkoxy and halogen, and C4-C20 hydroxyheteroaryl wherein the heteroatoms are selected from the group consisting of sulfur, nitrogen, and oxygen.
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- Process for the preparation of 3-benzoyl benzofuran derivatives
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The invention relates to a process for the preparation of 3-benzoyl benzofuran derivatives of general formula: STR1 wherein a benzofuran derivative of general formula: STR2 is reacted in situ in the presence of aluminium chloride successively with phosgene or oxalyl chloride, and then with a phenolic derivative of general formula: STR3 to produce a complex which is hydrolysed to form the desired compound of 3-benzoyl benzofuran.
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- Preparation of 2-alkyl-3-(4-hydroxybenzoyl)benzofuran
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The invention relates to new molecular complexes of general formula: STR1 in which R represents a straight- or branched-chain alkyl radical having from 1 to 4 carbon atoms and R1 represents one of the radicals: STR2 These molecular complexes are especially useful for the preparation of 2-alkyl-3-(4-hydroxybenzoyl)benzofurans.
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