- Synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials
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Malaria parasites are currently gaining drug-resistance rapidly, across countries and continents. Hence, the discovery and development of novel chemical scaffolds, with superior antimalarial activity remain an important priority, for the developing world. Our report describes the development, characterization and evaluation of novel bepotastine-based sulphonamide antimalarials inhibiting asexual stage development of Plasmodium falciparum parasites in vitro. The screening results showed potent inhibitory activity of a number of novel sulphonamides against P. falciparum at low micromolar concentrations, in particular in late-stage parasite development. Based on computational studies we hypothesize N-myristoyltransferase as the target of the compounds developed here. Our results demonstrate the value of novel bepotastine-based sulphonamide compounds for targeting the asexual developmental stages of P. falciparum.
- Anusha, Sebastian,Sinha, Ameya,Babu Rajeev,Chu, Trang T. T.,Mathai, Jessin,Ximei, Huang,Fuchs, Julian E.,Shivananju, Nanjundaswamy,Bender, Andreas,Preiser, Peter Rainer,Rangappa, Kanchugarakoppal S.,Basappa,Chandramohanadas, Rajesh
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- Total synthesis method of bestatin
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The method comprises the following steps: (4 - chlorophenyl) (2 - pyridyl) - methanol as a starting raw material, and sequential addition reaction. Examples of the etherification reaction include a deprotection reaction, a chiral resolution, a condensation reaction, a hydrolysis reaction, and the like. The synthesis method has the advantages of cheap and easily available raw materials, no need of expensive chiral catalysts, simpler synthesis method, mild conditions, less side reactions and low cost.
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- Light-induced metal-free transformations of unactivated pyridotriazoles
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A highly efficient and practical method for incorporation of the arylmethylpyridyl moiety into diverse molecules has been developed. This method features the transition metal-free light-induced room temperature transformation of pyridotriazoles into pyridyl carbenes, which are capable of smooth arylation, X-H insertion, and cyclopropanation reactions. The synthetic usefulness of the developed method was illustrated in a facile synthesis of biologically active molecules.
- Zhang, Ziyan,Yadagiri, Dongari,Gevorgyan, Vladimir
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p. 8399 - 8404
(2019/09/30)
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- Preparation method of 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine
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The invention discloses a preparation method of 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine. The method comprises the steps that alpha-(4-chlorobenzene ring)-2-pyridinemethanol and N-carbethoxy-4-pipradrol are adopted as starting raw materials, firstly, alpha-(4-chlorobenzne ring)-2-pyridinemethanol and N-carbethoxy-4-pipradrol are subjected to an etherification reaction under the catalysis of concentrated sulfuric acid to generate 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine-1-ethyl formate, then, the 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine-1-ethyl formate and sodium hydroxide are subjected to a hydrolysis reaction to generate a crude 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine, then, the crude 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine and fumaric acid form a salt to obtain a purified 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine fumarate, then, sodium hydroxide is used for ionization to finally obtain high-purity 4-[(4-chlorphenyl) (2-pyridyl) methoxyl] piperidine. The method is easy to implement, low in cost, high in product yield and capable of facilitating industrial conversion.
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Paragraph 0031
(2017/02/09)
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- METHOD OF SYNTHESIZING BEPOTASTINE OR BENZENESULFONIC ACID SALT THEREOF AND INTERMEDIATES USED THEREIN
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The present invention relates to a novel method of synthesizing bepotastine or its benzenesulfonic acid salt and novel intermediates used therein. The present invention uses L-α-hydroxy acid for chiral resolution to form an L-α-hydroxy acid salt of a compound represented by the following formula (VII-1), so as to synthesize bepotastine or its benzenesulfonic acid salt in high optical purity.
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- A novel synthetic method for bepotastine, a histamine H1 receptor antagonist
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An efficient and alternative synthesis of enantiomerically pure (+)-(S)-4-(4-((4-chlorophenyl)(pyrid-2-yl)methoxy]piperidin-1-yl)butanoic acid, bepotastine (1) is described. The key resolution of (R/S)-bepotastine l-menthyl ester (3) is achived via diastereomeric salt crystallization using N-benzyloxycarbonyl-L-aspartic acid (NCbzLAA) as the resolving agent to provide (S)-bepotastine l-menthyl ester (S)-3. Hydrolysis of (S)-bepotastine l-menthyl ester (S)-3 afforded the desired bepotastine (1) with good yields and enantiopurity (> 99%). Finally, bepotastine besilate (4) and bepotastine calcium (5) are achived by salt formation of bepotastine (1) with benzene sulfonic acid and calcium salt respectively. The reaction conditions were optimized to make suitable for commercial scale production.
- Ha, Tae Hee,Suh, Kwee-Hyun,Lee, Gwan Sun
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p. 549 - 552
(2013/08/25)
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- Acid-addition salts of optically active piperidine compound and process for producing the same
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The present invention is to provide a benzenesulfonic acid salt and a benzoic acid salt of (S)-4-[4-[(4-chlorophenyl) (2-pyridyl)methoxy]piperidino]butanoic acid represented by the formula (I): wherein * represents an asymmetric carbon, which are excellent in antihistaminic activity and anti-allergic activity, and a process for producing the same.
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