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. 2017 Dec 1;27(23):5190–5196. doi: 10.1016/j.bmcl.2017.10.042

Table 1.

Bedaquiline analogues containing heterocyclic ring units.

graphic file with name fx2.jpg

No R X (Class) Y MIC90 (µg/mL)a
 clog Pb
MABA LORA
1 Br Phenyl 2,3-Benz 0.05 0.08 7.25
3 Br A 3-CN 0.12 0.12 6.10
4 Br A 2,3-DiOMe 0.50 0.27 6.33
5 Br A 2-Aza, 3-OMe 0.12 0.15 5.99
6 Br A 3-Aza, 5-Me 0.58 0.30 5.67
7 CN A 3-Aza, 5-Me 1.94 1.10 4.24
8 Br A 3-Aza, 2-OMe 0.12 0.20 5.99
9 Br B 3-F 0.06 0.11 6.81
10 CN B 3-F 0.05 0.20 4.67
11c Br C 3-F 0.47d 5.01
12 Br C 3-Aza, 2-OMe 0.22 0.52 5.55
13 Br D 3-Aza, 2-OMe 0.24 0.53 5.09
14c CN D 3-F 0.70d 4.55
15c Br E 3-F 0.74d 5.40
16c CN E 3-F 1.79d 4.02
17c Br E 3-OCF3 0.76d 7.51
18c Br E 2,3-DiOMe 0.71d 6.14
19c Br E 2,3-OCH2O- 0.69d 6.45
20c Br E 2-Aza 1.95d 4.98
21c Br E 3-CN 1.96d 4.69
22c Br F 3-F 0.74d 5.40
23c CN F 3-F 1.08d 4.04
24c Br F 2-Aza, 3-F 0.68d 5.00
25c Br F 3-OCF3 0.76d 7.30
26c Br F 2,3-DiOMe 1.16d 5.93
27c Br F 2,3-OCH2O– 0.90d 6.23
28c Br F 2-Aza 1.80d 4.77
29c Br G; Z = 2-OMe 3-F 0.12d 5.14
30 Br G; Z = 2-OMe 3-Me 0.13 0.25 5.50
31 CN G; Z = 2-OMe 3-Me 0.30 0.15 4.16
32c Br G; Z = 2-OMe 2,3-DiOMe 0.24d 4.66
33 Br G; Z = 2-OMe 3-CN 0.34 0.75 4.43
34 CN G; Z = 2-OMe 3-CN 0.38 0.82 3.07
35 Br G; Z = 2-NMe2 3-F 0.18 0.20 5.44
36 Br G; Z = 4-NMe2 3-F 0.08 0.15 5.44
37 Br G; Z = 4-NEt2 3-F 0.02 0.02 6.49
38 Br G; Z = 4-SMe 3-F 0.14 0.37 5.86
39 Br G; Z = 4-SEt 3-F 0.14 0.15 6.39
40 Br G; Z = 5-Me 3-OMe 1.9 2.2 5.00
41 Br G; Z = 5-Me 3-CN 1.32 3.38 4.51
42 Br G; Z = 5-Me 3-F 0.53 0.97 5.22
43 Br G; Z = 4,5-diOMe 3-F 0.47 0.54 5.59
44 Br H; Z = 2,3-diOMe 3-F 0.02 0.07 5.19
45 Br H; Z = 2,3-diOMe 3-Me 0.02 0.04 5.55
46 CN H; Z = 2,3-diOMe 3-Me 0.15 0.14 4.19
47 Br H; Z = 2,3-diOMe 3-OMe <0.02 <0.02 5.00
48 Br H; Z = 2,3-diOMe 3-OCF2H <0.02 <0.02 5.41
49 Br H; Z = 2,3-diOMe 3-CN 0.13 0.21 4.48
50 Br H; Z = 2,3-diOMe 2,3-DiOMe 0.21d 4.71
a

MIC90 (μg/mL); minimum inhibitory concentration for 90% inhibition of growth of M.tb strain H37Rv, determined under aerobic (replicating; MABA) (Ref. 16) or non-replicating (LORA) (Ref. 17) conditions, determined at the Institute for Tuberculosis Research, University of Illinois at Chicago. Each value is the mean of at least two independent determinations.

b

clog P calculated by ChemDraw Ultra v12.0.2. (CambridgeSoft).

c

RS/SR racemic mixture.

d

MICs determined at Tibotec (Mechelen, Belgium).