873203-37-3Relevant academic research and scientific papers
Scalable Multigram Syntheses of Antimalarial 4(1H)-Quinolones ELQ-300 and P4Q-391
Namelikonda, Niranjan K.,Monastyrskyi, Andrii,Manetsch, Roman
, p. 3328 - 3334 (2017/06/29)
Antimalarial compounds ELQ-300 and P4Q-391 are highly potent against the blood and the liver stages of the Plasmodium parasite and also possess potent transmission-blocking activity. Gram amounts of these two compounds were required for extensive assessment of in vivo efficacy, pharmacokinetics, and safety. Several deficiencies existed in the original synthetic routes of ELQ-300 and P4Q-391 including reliance on toxic heavy-metal reagents, harsh reaction conditions, and several low-yielding steps. Herein, we report the development of two alternative syntheses, which are reliable, high yielding, scalable, and have the potential to become a route of choice at process scale.
Metal-free arylation of ethyl acetoacetate with hypervalent diaryliodonium salts: An immediate access to diverse 3-aryl-4(1 H)-quinolones
Monastyrskyi, Andrii,Namelikonda, Niranjan K.,Manetsch, Roman
, p. 2513 - 2520 (2015/03/18)
A clean arylation protocol of ethyl acetoacetate was developed using hypervalent diaryliodonium salts under mild and metal-free conditions. The scope of the reaction, using symmetric and unsymmetric iodonium salts with varying sterics and electronics, was examined. Further, this method has been applied for the synthesis of antimalarial compound ELQ-300, which is currently in preclinical development.
Synthesis and Structure-Activity Relationships for Extended Side Chain Analogues of the Antitubercular Drug (6 S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5 H -imidazo[2,1- b ][1,3]oxazine (PA-824)
Palmer, Brian D.,Sutherland, Hamish S.,Blaser, Adrian,Kmentova, Iveta,Franzblau, Scott G.,Wan, Baojie,Wang, Yuehong,Ma, Zhenkun,Denny, William A.,Thompson, Andrew M.
, p. 3036 - 3059 (2015/04/27)
Novel extended side chain nitroimidazooxazine analogues featuring diverse linker groups between two aryl rings were studied as a potential strategy to improve solubility and oral activity against chronic infection by Mycobacterium tuberculosis. Both lipop
PYRIMIDINE CARBOXAMIDES AS SODIUM CHANNEL BLOCKERS
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Paragraph 0380, (2014/09/29)
The present disclosure provides substituted pyrimidine carboxamides of Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein A1, X, A2, W1, W2, W3, E, Z, and R4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.
PYRIMIDINES AS SODIUM CHANNEL BLOCKERS
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Page/Page column 146; 147, (2013/03/28)
The present disclosure provides substituted pyrimidine compounds of Formula (I), and the pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein A1, X, A2, W1, W2, W3, E, Z, and R4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.
