- An Integrated Continuous Flow Micro-Total Ultrafast Process System (μ-TUFPS) for the Synthesis of Celecoxib and Other Cyclooxygenase Inhibitors
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Integrated continuous manufacturing has emerged as a promising device for the rapid manufacturing of active pharmaceutical ingredients (APIs). We herein report a newly designed continuous flow micro-total process system platform for the rapid manufacturing of celecoxib, a selective nonsteroidal anti-inflammatory drug. This approach has been proven generally for the synthesis of several alkyl and aryl substituted pyrazoles. In order to minimize the tedious work-up process of potential reaction intermediates/products, we have developed a continuous flow extraction and separation platform to carry out the entire reaction sequence resulting in a short residence time with good yield. The present process was further extended to gram-scale synthesis of the COX-2-related API, viz. celecoxib, in the continuous flow process.
- Sthalam, Vinay Kumar,Singh, Ajay K.,Pabbaraja, Srihari
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supporting information
p. 1892 - 1899
(2019/10/11)
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- A Sequential Route to Cyclopentenes from 1,6-Enynes and Diazo Ketones through Gold and Rhodium Catalysis
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This work reports the construction of cyclopentene cores from 1,6-enynes and aryl diazo ketones through two new reaction sequences involving initial gold-catalyzed cyclization of 1,6-enynes with diazo species, followed by rhodium-catalyzed skeletal rearrangement of the resulting 3-cyclopropyl-2-en-1-ones. In most instances the rhodium-catalyzed reactions afforded cyclopentene derivatives whereas several n-alkyl- or ortho-substituted phenyl ketones delivered seven-membered oxacycles. A plausible mechanism provides rationales for these two distinct products. (Figure presented.).
- Kale, Balaji S.,Lee, Hsin-Fu,Liu, Rai-Shung
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supporting information
p. 402 - 409
(2017/02/10)
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- Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus
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Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health because of its resistance to multiple antibiotics most commonly used to treat infection. In this study, we report the unique ability of the cyclooxygenase-2 (COX-2) inhibitor celecoxib to kill Staphylococcus aureus and MRSA with modest potency. We hypothesize that the anti-Staphylococcus activity of celecoxib could be pharmacologically exploited to develop novel anti-MRSA agents with a distinct mechanism. Examination of an in-house, celecoxib-based focused compound library in conjunction with structural modifications led to the identification of compound 46 as the lead agent with high antibacterial potency against a panel of Staphylococcus pathogens and different strains of MRSA. Moreover, this killing effect is bacteria-specific, as human cancer cells are resistant to 46. In addition, a single intraperitoneal administration of compound 46 at 30 mg/kg improved the survival of MRSA-infected C57BL/6 mice. In light of its high potency in eradicating MRSA in vitro and its in vivo activity, compound 46 and its analogues warrant continued preclinical development as a potential therapeutic intervention against MRSA.
- Chiu, Hao-Chieh,Lee, Su-Lin,Kapuriya, Naval,Wang, Dasheng,Chen, Yi-Ru,Yu, Sung-Liang,Kulp, Samuel K.,Teng, Lee-Jene,Chen, Ching-Shih
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experimental part
p. 4653 - 4660
(2012/08/29)
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- First synthesis of functionalized 5-aryl-3-(trifluoromethyl)phenols by regioselective [3+3] cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes with 3-aryl-3-silyloxy-1-trifluoromethyl-2-en-1-ones
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A variety of functionalized 5-aryl-3-(trifluoromethyl)phenols were prepared by the first TiCl4-mediated [3+3] cyclocondensation of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-aryl-3-trimethylsilyloxy-1-trifluoromethyl-2-en-1-ones.
- Büttner, Stefan,Riahi, Abdolmajid,Hussain, Ibrar,Yawer, Mirza A.,Lubbe, Mathias,Villinger, Alexander,Reinke, Helmut,Fischer, Christine,Langer, Peter
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experimental part
p. 2124 - 2135
(2009/07/18)
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