. Author manuscript; available in PMC: 2012 Jul 1.

Published in final edited form as: Future Med Chem. 2011 Sep;3(11):1427–1454. doi: 10.4155/fmc.11.90

Table 9.

Structure–activity relationships of selected five-membered heterobiaryl analogs of PA-824 (5)^†.


Compound number	Substituent X	MIC (µM)		Microsomal stability after 1 h (ratio remaining)		In vivo efficacy (% relative to PA-824, (5))
Compound number	Substituent X	MABA	LORA	Human	Mouse	In vivo efficacy (% relative to PA-824, (5))
5		0.5	2.6	0.82	0.94	100
106		0.035	1.3	0.97	0.96	>25000
123		0.06	0.58	0.86	0.81	1200
124		0.05	0.61	0.87	0.67	4100
125		0.075	3.3	0.99	0.74	34
126		0.035	1.3	0.97	0.81	4300

^†

Data from [34].

LORA: Low-oxygen recovery assay where hypoxically adapted cells are incubated with compound under anaerobic conditions followed by an aerobic recovery to measure luminescence as a surrogate readout of the number of cells prior to recovery; MABA: Microplate Alamar blue assay, aerobic MIC as determined by Alamar Blue-based readout of redox activity in cells; MIC: Minimum inhibitory concentration.