Table 2. Comparison of Different 6-Quinoline Substituents on Modified B/C Scaffolds.

#	B-ring substituent	C-ring substituent	X	clogPa	MIC90b	clog P/M.tb scorec
1	H	1-naphthyl	Br	7.25	0.09
27	H	3-F	Br	6.22	0.23
28			CN	4.86	0.69	3.0
29			C≡CH	5.60	0.36	4.8
30			NMeSO2Ph	6.39	4.1d	–0.04
31			NMeSO2NMe2	4.20	5d	0.42
32	3-F	3-OCF3	Br	7.25	0.25
33			CN	5.89	0.47	6.2
34			N(CH2CH2)2O	6.22	0.85	1.7
35			Cl	7.10	0.09	–0.94
36	2-F, 3-OMe	3-F	Br	6.22	0.10
37			CN	4.87	0.18	17
38			Xe	5.04	0.51d	2.9
39			N(CH2CH2)2S	6.03	0.19d	2.1
40			N(CH2CH2)2SO2	4.23	>5d	0.41
41			N(CH2CH2)2SO	4.31	>5d	0.39
42			SMe	6.03	0.13d	6.3
43			SO2Me	4.11	2.3d	0.96
44	2-F, 3-OMe	3-OCF3	Br	7.11	0.09
45			CN	5.75	0.26	8.0
46			Xe	5.92	0.77	1.8
47			N(CH2CH2)2O	6.08	0.14	21
48			N(CH2CH2)2NH	6.07	0.66	1.8
49			Npiperidyl	7.46	2.3	–0.16
50			F	6.39	0.21	6.0
51			OCF3	7.60	1.1	–0.51
52	2-F, 3-OMe	3-OMe	Br	6.00	0.10
53			CN	4.64	0.09	–130.0f
54			Xe	4.81	0.87d	1.5
55	2-F, 3-OMe	3-Cl	Br	6.79	0.07
56			CN	5.44	0.13	23
57			Xe	5.61	0.31d	4.9
58	2-F, 3-OMe	3-Me	Br	6.58	0.04
59			CN	5.22	0.09	30
60			Xe	5.39	1.1d	1.1
61	2,3-diOMe	3-F	Br	5.48	0.04
62			CN	4.12	0.17	11
63			Xe	4.29	0.66	1.9
64			N(CH2CH2)2S	5.28	0.28d	0.83
65			N(CH2CH2)2SO2	3.49	>5d	0.40
66			N(CH2CH2)2SO	3.57	4.8d	0.40
67			NMeSO2NMe2	3.45	1.13d	1.9
68	2,3-diOMe	2,3-diOMe	Br	4.99	0.20
69			CN	3.64	0.34	9.6
70			N(CH2CH2)2O	3.97	2.5	0.44
71			Cl	4.84	0.25	3.0
72	2,3-diOMe	3-OCF3	Br	6.36	0.09
73			CN	5.01	0.21	11
74			Xe	5.18	0.75	1.8
75			N(CH2CH2)2O	5.34	0.68	1.7

^aclogP calculated by ChemDraw v.13.0 (CambridgeSoft).

^bMIC₉₀ (in μg/mL) for inhibition of M.tb.

^cclog P/M.tb score = clogP_(Br) – clogP_(Xsub)/MIC_90(Xsub) – MIC_90(Br).

^dData for R,S enantiomer.

^eFor X, see compound 26 in Table 1.

^fThis value was not included as a data point for Figure 2, as the CN analogue was more potent than the Br, producing a negative score.