Table 7.

MbtA Inhibitors: Nucleobase Domain SAR

Compound, R =		KIapp (μM)	MIC99(μM) (iron-deficient)	MIC99 (μM) (iron-rich)
	51, X = Y = N	0.0066 ± 0.0015	0.39	1.56
	80, X = N; Y = CH	0.0243 ± 0.0070	6.25	50
	81, X = Y= CH	0.0201 ± 0.0023	6.25	50
	82, =O	0.80 ± 0.05	>100	>100
	83, –NMe2	0.38 ± 0.03	50	n.d.
	84, –NHMe	0.0016 ± 0.0002	0.39	1.56
	85, –NHEt	0.0044 ± 0.0008	0.39	1.56
	86, –NHn-Pr	0.0035 ± 0.0002	0.39	1.56
	87, –NHi-Pr	0.0070 ± 0.0009	25	>100
	88, –NHi-Bu	1.14 ± 0.23	>100	>100
	89, –NHcyclopropy	0.0019 ± 0.0001	0.098	6.25
	90, –NHcyclobutyl	0.124 ± 0.012	>100	>100
	91, –NHcyclopenty	9.4 ± 5.2	>100	>100
	92, –NHBn	8.3 ± 0.8	>100	>100
	93, –Br	2.05 ± 0.30	>50	>50
	94, –N3	42.5 ± 6.2	>50	>50
	95, –NH2	183 ± 19	>50	>50
	96, –I	0.0030 ± 0.0003	0.19	3.12
	97, –NHPh	0.0009 ± 0.0002	0.049	0.39
	98, –CCPh	0.0004 ± 0.0001	0.049	0.39
	99, –Ph	0.0003 ± 0.0001	0.049	0.39
	100, biphen-2-yl	0.047 ± 0.002	>50	>50
	101, biphen-3-yl	0.0014 ± 0.0002	3.13–6.25	12.5–25
	102, biphen-4-y	0.0010 ± 0.00002	3.13–6.25	12.5–25
	103	0.0033 ± 0.0003	3.13	>50
	104	0.0027 ± 0.0004	>25	>50