1 research outputs found
Biarylmethoxy Nicotinamides As Novel and Specific Inhibitors of <i>Mycobacterium tuberculosis</i>
A whole cell based screening effort
on a focused library from corporate
collection resulted in the identification of biarylmethoxy nicotinamides
as novel inhibitors of <i>M. tuberculosis</i> (Mtu) H37Rv.
The series exhibited tangible structure–activity relationships,
and during hit to lead exploration, a cellular potency of 100 nM was
achieved, which is an improvement of >200-fold from the starting
point.
The series is very specific to Mtu and noncytotoxic up to 250 μM
as measured in the mammalian cell line THP-1 based cytotoxicity assay.
This compound class retains its potency on several drug sensitive
and single drug resistant clinical isolates, which indicate that the
compounds could be acting through a novel mode of action