50275-07-5Relevant academic research and scientific papers
Quinolone carboxylic acids as a novel monoketo acid class of human immunodeficiency virus type 1 integrase inhibitors
Sato, Motohide,Kawakami, Hiroshi,Motomura, Takahisa,Aramaki, Hisateru,Matsuda, Takashi,Yamashita, Masaki,Ito, Yoshiharu,Matsuzaki, Yuji,Yamataka, Kazunobu,Ikeda, Satoru,Shinkai, Hisashi
supporting information; experimental part, p. 4869 - 4882 (2010/03/02)
Human immunodeficiency virus type 1 (HIV-1) integrase is a crucial target for antiretroviral drugs, and several keto - enol acid class (often referred to as diketo acid class) inhibitors have clinically exhibited-marked antiretroviral activity. Here, we show the synthesis and the detailed structure - activity relationship of the quinolone carboxylic acids as a novel monoketo acid class of integrase inhibitors. 6-(3-Chloro-2-fluorobenzyl)-1-((2S)-1-hydroxy-3,3- dimethylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 51, which showed an IC50 of 5.8 nMin the strand transfer assay and an ED50 of 0.6 nMin the antiviral assay, and 6-(3-chloro-2-fluorobenzyl) -1-((2S)-1-hydroxy-3-methylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3- carboxylic acid 49, which had an IC50 of 7.2 nMand an ED50 of 0.9 nM, were the most potent compounds in this class. The monoketo acid 49 was much more potent at inhibiting integrasecatalyzed strand transfer processes than 3′-processing reactions, as is the case with the keto - enol acids. Elvitegravir 49 was chosen as a candidate for further studies and is currently in phase 3 clinical trials.
N-phenyl-2-cyano-3-hydroxy-propenamides
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, (2008/06/13)
A compound selected from the group consisting of a compound of the formula STR1 wherein R1 is selected from the group consisting of alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms and alkenyl and alkynyl of 2 to 6 carbon atoms, R2 is hydrogen or alkyl of 1 to 3 carbon atoms, Y is selected from the group consisting of STR2 Z1 and Z2 are individually selected from the group consisting of hydrogen, halogen, --NO2, --CN and alkyl of 1 to 3 carbon atoms, R3 is hydrogen or alkyl of 1 to 3 carbon atoms, m is an integer from 0 to 6, R4, R5, R6, R7 and R8 are individually selected from the group consisting of hydrogen, halogen, --CN, --NO2, alkyl, alkylthio and alkoxy of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, --COR10, --(CH2)n --CX3, --O--(CH2)n CX3 and --S--(CH2)n --CX3, R10 is selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms and cycloalkyl of 3 to 6 carbon atoms, n is an integer from 0 to 3, X is halogen or R6 and R7 together form --O--CH2 --O-- and their non-toxic, pharmaceutically acceptable salts with a base having anti-inflammatory and immunomodulatory activity.
