Nanomolar inhibitors of Mycobacterium tuberculosis glutamine synthetase 1: synthesis, biological evaluation and X-ray crystallographic studies.
Couturier C, Silve S, Morales R, Pessegue B, Llopart S, Nair A, Bauer A, Scheiper B, Pöverlein C, Ganzhorn A, Lagrange S, Bacqué E.
A series of imidazo[1,2-a]indeno[1,2-e]pyrazin-4-ones that potently inhibit M. tuberculosis glutamine synthetase (GlnA1) has been identified by high throughput screening. Exploration of this series was performed owing to a short chemistry program. Despite possibly nanomolar inhibitions, none of these compounds was active on whole cell Mtb, suggesting that GlnA1 may not be a suitable target to find new anti-tubercular drugs.