1428554-10-2Relevant academic research and scientific papers
Synthesis and structure-activity relationships of phenyl-substituted coumarins with anti-tubercular activity that target FadD32
Kawate, Tomohiko,Iwase, Noriaki,Shimizu, Motohisa,Stanley, Sarah A.,Wellington, Samantha,Kazyanskaya, Edward,Hung, Deborah T.
, p. 6052 - 6059 (2013)
In an effort to develop new and potent agents for therapy against tuberculosis, a high-throughput screen was performed against Mycobacterium tuberculosis strain H37Rv. Two 6-aryl-5,7-dimethyl-4-phenylcoumarin compounds 1a and 1b were found with modest activity. A series of coumarin derivatives were synthesized to improve potency and to investigate the structure-activity relationship of the series. Among them, compounds 1o and 2d showed improved activity with IC90 of 2 μM and 0.5 μM, respectively. Further optimization provided compound 3b with better physiochemical properties with IC90 0.4 μM which had activity in a mouse model of infection. The role of the conformation of the 4- and 6-aryl substituents is also described.
