71058-39-4Relevant academic research and scientific papers
Pyrrolo[3,4-c]pyridine-1,3(2H)-diones: A novel antimycobacterial class targeting mycobacterial respiration
Van Der Westhuyzen, Renier,Winks, Susan,Wilson, Colin R.,Boyle, Grant A.,Gessner, Richard K.,Soares De Melo, Candice,Taylor, Dale,De Kock, Carmen,Njoroge, Mathew,Brunschwig, Christel,Lawrence, Nina,Rao, Srinivasa P.S.,Sirgel, Frederick,Van Helden, Paul,Seldon, Ronnett,Moosa, Atica,Warner, Digby F.,Arista, Luca,Manjunatha, Ujjini H.,Smith, Paul W.,Street, Leslie J.,Chibale, Kelly
, p. 9371 - 9381 (2015)
High-throughput screening of a library of small polar molecules against Mycobacterium tuberculosis led to the identification of a phthalimide-containing ester hit compound (1), which was optimized for metabolic stability by replacing the ester moiety with a methyl oxadiazole bioisostere. A route utilizing polymer-supported reagents was designed and executed to explore structure-activity relationships with respect to the N-benzyl substituent, leading to compounds with nanomolar activity. The frontrunner compound (5h) from these studies was well tolerated in mice. A M. tuberculosis cytochrome bd oxidase deletion mutant (ΔcydKO) was hyper-susceptible to compounds from this series, and a strain carrying a single point mutation in qcrB, the gene encoding a subunit of the menaquinol cytochrome c oxidoreductase, was resistant to compounds in this series. In combination, these observations indicate that this novel class of antimycobacterial compounds inhibits the cytochrome bc1 complex, a validated drug target in M. tuberculosis.
A One-Pot Synthesis of 3-Aminopyridines
Shimada, Sadakatsu,Maeda, Hiroshi
, p. 3460 - 3464 (2007/10/02)
The reaction of N-(cyanophenylmethyl)acylamides (1) with olefins (2) in the presence of trifluoroacetic acid gave the corresponding 3-amino-2-phenylpyridines (3) in good yields.Similar reaction of ethyl 2-acylamino-2-cyanoacetates (4) with olefins in the
