, Chloroquinolin-4-yl)amino)octyl)-3-(1,3-dioxoisoindolin-2-yl)propanamide (7h). Yield 70%; white solid, HRMS calcd for C 26 H 27 ClN 4 O 3

1. Hz and A. Ar-h)-;-m,-4h, 20-8.30 (m, 2H, Ar-H + NH-exchangeable with D 2 O); 8.34 (d, J ¼ 5.3 Hz, 1H, Ar-H); 13 C NMR (100 MHz, DMSO-d 6 ), vol.7

2. Hz and -. Ch,

, Ar-H); 7.77 (dd, J ¼ 2.2, 9.1 Hz, vol.1

, -Chloroquinolin-4-yl)amino)butyl)-4-(1,3-dioxoisoindolin-2-yl)butanamide (7j). Yield 74%; white solid, 54 (t, J ¼ 5.9 Hz, vol.2

D. and J. ¼. , Hz, vol.1, p.85

, 86 (m, 4H, Ar-H); 8.01 (d, J ¼ 2.1 Hz, 1H, Ar-H), vol.8, pp.80-87

1. Hz and . Nh-, , vol.2

C. Nmr, 85 (t, J ¼ 5.5 Hz, 1H, NH-exchangeable with D 2 O), vol.13, p.125

D. Mhz, -Chloroquinolin-4-yl)amino)hexyl)-4-(1,3-dioxoisoindolin-2-yl)butanamide (7k). Yield 75%; white solid

, .67 (m, 2H, pp.61-62

, 27 (m, 2H, pp.23-26

D. and J. ¼. , , vol.6

1. Hz and A. , 86 (m, 4H, Ar-H); 8.28 (d, J ¼ 9.0 Hz, 1H, Ar-H); 8.38 (t, J ¼ 5.5 Hz, 1H, NH-exchangeable with D 2 O); 13 C NMR (125 MHz, DMSO-d 6 ), vol.1, pp.81-88

, Ar-H); 7.75 (d, J ¼ 2.3 Hz, 1H, Ar-H); 7.83-7.90 (m, 4H, Ar-H); 8.19 (d, J ¼ 5.4 Hz, 1H, Ar-H), vol.1, p.27

2. Ar and -. Nh, Ar-H); 8.13 (d, J ¼ 9.0 Hz, Ar-H); 8.37 (d, J ¼ 5.5 Hz, Ar-H); 8.45 (t, J ¼ 5.6 Hz, 1H, NH-exchangeable with D 2 O); 13 C NMR (125 MHz, DMSO-d 6 ), 167.3, 169.7. HRMS calcd for C 2 1H 16 ClFN 4 O 3, vol.1

2. Ar and -. Nh, 99 (m, 1H, Ar-H); 8.25 (t, J ¼ 5.7 Hz, NH-exchangeable with D 2 O); 8.29 (d, J ¼ 9.0 Hz, Ar-H); 8.39 (d, J ¼ 5.5 Hz, 1H, Ar-H); 13 C NMR (125 MHz, DMSO-d 6 ), vol.1, p.2

2. and -. Ch, 17 (s, 2H, -CH 2 -); 6.39 (d, J ¼ 5.3 Hz, 1H, Ar-H); 7.30 (t, J ¼ 5.4 Hz, NH-exchangeable with D 2 O), vol.4

N. H. Hz,

, Ar-H); 13 C NMR (100 MHz, DMSO-d 6 ), vol.1

. Hz, , vol.121

. Hz, 127.8, 128.2 (d, J ¼ 1.9 Hz), 133.7, 135.1 (d, J ¼ 9

, Chloroquinolin-4-yl)amino)ethyl)-3-(5-?uoro-1,3-dioxoisoindolin-2-yl)propanamide (7p)

2. Hz and -. Ch,

, m, 4H, 2Â -CH 2 -

2. Hz and -. Ch,

N. H. Hz, , vol.1

, Ar-H); 8.35 (d, J ¼ 5.5 Hz, 1H, Ar-H); 13 C NMR (100 MHz, DMSO-d 6 )

, + 492.1928 found 4921941. HRMS calcd for C 22 H 18 ClFN, vol.4

+. , Chloroquinolin-4-yl)amino)butyl)-3-(5-?uoro-1,3-dioxoisoindolin-2-yl)propanamide (7q)

H. Nmr, 400 MHz): 1.38-1.45 (m, 2H, pp.177-178

1. Hz, . Ar-h)-;-m,-1h, . Ar-h)-;-m,-2h, and A. Ar-h)-;-m,-1h, 98 (t, J ¼ 5.5 Hz, NHexchangeable with D 2 O); 8.21 (d, J ¼ 9.0 Hz, Ar-H); 8.33 (d, J ¼ 5.4 Hz, 1H, Ar-H); 13 C NMR (100 MHz, DMSO-d 6 ), vol.7

2. Hz and -. Ch,

1. Ar-h)-;-m,-2h and A. , NHexchangeable with D 2 O); 8.20 (d, J ¼ 9.1 Hz, Ar-H); 8.32 (d, J ¼ 5.3 Hz, 1H, Ar-H), .89 (m, 1H, Ar-H); 7.95 (t, J ¼ 5.4 Hz, vol.1, p.3

, A?er sealing with a PTFE cap, the vessel was heated to 160 C for 5 min in the microwave reactor and the completion was ascertained using TLC. A?er completion, the contents were poured in water (20 mL) resulting in the precipitation of the desired product. The yellow product obtained was ?ltered and recrystallized using absolute ethanol

, DMSO-d 6 ) d 3.30-3.32 (m, 6H, 3Â -CH 2 -); 3.59-3.63 (m, 2H, -CH 2 -); 3.74-3.76 (m, 4H, 2Â -CH 2 -), vol.1

, Ar-H); 7.77 (dd, J ¼ 2.0, 9.0 Hz, 1H, Ar-H); 8.05 (d, J ¼ 2.1 Hz, 1H, Ar-H); 8.55-8.57 (m, 3H, Ar-H), vol.1, p.125

D. Mhz, Chloroquinolin-4-yl)amino)butyl)-2-(5-morpholino-1,3-dioxoisoindolin-2-yl)acetamide (8b)

D. and J. ¼. , , vol.6

1. Hz and A. , , vol.7

1. Hz and . Nh-, Ar-H); 7.68 (d, J ¼ 8.8 Hz, 1H, Ar-H); 7.79 (d, J ¼ 2.1 Hz, 1H, Ar-H); 8.16 (t, J ¼ 5.5 Hz, 1H, NH-exchangeable with D 2 O); 8.27 (d, J ¼ 9, Ar-H); 7.45 (dd, J ¼ 2.0, 9.0 Hz, vol.1

+. , Chloroquinolin-4-yl)amino)hexyl)-2-(5-morpholino-1,3-dioxoisoindolin-2-yl)acetamide (8c)

, DMSO-d 6 ) d 1.30-1.45 (m, 6H, 3Â -CH 2 -); 1.64-1.67 (m, 2H

, m, 4H, 2Â -CH 2 -

1. Hz and J. Ar-h)-;-t, , vol.7

1. Hz and . Nh-, Ar-H); 7.77 (d, J ¼ 2.2 Hz, 1H, Ar-H); 8.15 (t, J ¼ 5.6 Hz, 1H, NH-exchangeable with D 2 O); 8.26 (d, J ¼ 9, Hz, vol.1, issue.7

, 28 (m, 8H, 4Â -CH 2 -); 3.67-3.73 (m, 6H, 3Â -CH 2 -), pp.20-23

, Ar-H); 7.06 (dd, J ¼ 2.3, 8.4 Hz, 1H, Ar-H), vol.1

1. Hz and J. Ar-h)-;-d, 50 (d, J ¼ 8.6 Hz, 1H, Ar-H), vol.7

1. Hz and A. , , vol.8

1. Hz and N. , -Chloroquinolin-4-yl)amino)butyl)-3-(5-morpholino-1,3-dioxoisoindolin-2-yl)propanamide (8e). Yield 82%; Yellow solid, C NMR (100 MHz, vol.1

, .67 (m, 2H, vol.6, p.3

, Ar-H); 7.04 (dd, J ¼ 2.2, 8.7 Hz, 1H, Ar-H); 7.14 (d, J ¼ 2.2 Hz, 1H, Ar-H), vol.1

, -Chloroquinolin-4-yl)amino)hexyl)-3-(5-morpholino-1,3-dioxoisoindolin-2-yl)propanamide (8f). Yield 78%; yellow solid, vol.1

, 27 (m, 2H, pp.23-26

, m, 4H, 2Â -CH 2 -); 3.66-3.73 (m, 6H, 3Â -CH 2 -

, Ar-H); 7.03 (dd, J ¼ 2.1, 8.6 Hz, 1H, Ar-H); 7.15 (d, J ¼ 2.1 Hz, vol.1

, Ar-H); 8.26 (t, J ¼ 5.3 Hz, 1H, N-Hexchangeable with D 2 O); 8.34 (d, J ¼ 5.3 Hz, 1H, Ar-H), C NMR (100 MHz, vol.1

, 3-dioxoisoindolin-2-yl)acetamide (8g)

, m, 4H, 2Â -CH 2 -

1. Hz and A. , m, 2H, Ar-H, NHexchangeable with D 2 O); 7.56 (d, J ¼ 8.6 Hz, 1H, Ar-H, vol.6, p.100

D. Mhz,

, 3-dioxoisoindolin-2-yl)acetamide (8h)

, m, 2H, -CH 2 -, vol.1

, m, 2H, 2Â -CH 2 -, vol.3

, 99 (s, 1H, vol.1

1. and A. , 18 (t, J ¼ 5.2 Hz, 1H, NH-exchangeable with D 2 O), vol.8

C. Nmr,

, 3-dioxoisoindolin-2-yl)acetamide (8i)

, 10 (m, 2H, -CH 2 -); 3.25-3.30 (m, 2H, 2Â -CH 2 -), vol.3, pp.7-10

, Ar-H); 6.90 (dd, J ¼ 2.2, 8.8 Hz, 1H, Ar-H); 6.98 (d, vol.1

1. Hz and . Nh-,

1. Hz and A. , , vol.8

, 3-dioxoisoindolin-2-yl)propanamide (8j)

, m, 4H, 2Â -CH 2 -

, Ar-H); 6.76 (dd, vol.1

, Ar-H); 8.23 (t, J ¼ 5.3 Hz, 1H, NH-exchangeable with D 2 O); 8.35 (d, J ¼ 5.0 Hz, 1H, Ar-H); 13 C NMR (100 MHz, DMSO-d 6 ), vol.1

, 3-dioxoisoindolin-2-yl)propanamide (8k)

6. Hz, m, 2H, -CH 2 -); 1.60-1.67 (m, 2H, -CH 2 -, vol.1

, 25-3.30 (m, 2H

, m, 4H, 2Â -CH 2 -

2. Hz and -. Ch,

1. Hz and A. , Ar-H); 8.25 (t, J ¼ 5.3 Hz, 1H, NH-exchangeable with D 2 O); 8.36 (d, J ¼ 5.2 Hz, 1H, Ar-H); 13 C NMR (100 MHz, DMSO-d 6 ), Hz, vol.6

, 3-dioxoisoindolin-2-yl)propanamide (8l)

, DMSO-d 6 ) d 1.08 (t, J ¼ 7.3 Hz, 6H, 2Â -CH 3 ); 1.35-1.45 (m, 6H, 3Â -CH 2 -), vol.1, pp.61-62

, 24-3.30 (m, 2H

, m, 4H, 2Â -CH 2 -

2. Hz and -. Ch,

1. Hz and A. , Ar-H); 8.26 (t, J ¼ 5.3 Hz, 1H, NH-exchangeable with D 2 O); 8.38 (d, J ¼ 5.2 Hz, 1H, Ar-H); 13 C NMR (100 MHz, DMSO-d 6 ), Hz, vol.6

, 3-dioxoisoindolin-2-yl)acetamide (8m), vol.2

, Ar-H); 7.21 (dd, J ¼ 1.5, 8.6 Hz, 1H, Ar-H); 7.30 (d, J ¼ 1.4 Hz, 1H, Ar-H), vol.1

1. Hz and . Nh-,

1. Hz and A. , Ar-H), C NMR (125 MHz, DMSO-d 6 ), vol.1

, 3-dioxoisoindolin-2-yl)acetamide (8n)

, (m, 2H, -CH 2 -); 2.44 (t, J ¼ 6.1 Hz 2H

1. Hz and A. , Ar-H); 7.65 (d, J ¼ 8.5 Hz, 1H, Ar-H); 7.77 (d, J ¼ 2.0 Hz, 1H, Ar-H); 8.19 (t, J ¼ 5.7 Hz, 1H, NHexchangeable with D 2 O), vol.1

, 3-dioxoisoindolin-2-yl)acetamide (8o)

2. and -. Ch,

, Ar-H), vol.1

, Ar-H); 7.75 (d, J ¼ 2.0 Hz, 1H, Ar-H); 8.16 (t, J ¼ 5.5 Hz, 1H, NH-exchangeable with D 2 O); 8.25 (d, J ¼ 9.0 Hz, 1H, Ar-H); 8.36 (d, J ¼ 5.3 Hz, 1H, Ar-H), C NMR (125 MHz, vol.1

, 3-dioxoisoindolin-2-yl)propanamide (8p), vol.1

, Ar-H), vol.1, p.49

, 28 (t, J ¼ 5.2 Hz, 1H, NHexchangeable with D 2 O); 7.40 (dd, vol.7

1. Hz and A. , NH-exchangeable with D 2 O); 8.39 (d, J ¼ 5.4 Hz, 1H, Ar-H); 13 C NMR (125 MHz, DMSO-d 6 ), vol.1

, 3-dioxoisoindolin-2-yl)propanamide (8q), vol.1

, 48 (s, 1H, OH); 6.47 (d, J ¼ 5.5 Hz, 1H, Ar-H), vol.2

1. Hz and A. , NH-exchangeable with D 2 O); 8.40 (d, J ¼ 5.3 Hz, 1H, Ar-H); 13 C NMR (125 MHz, DMSO-d 6 ), vol.8

, 3-dioxoisoindolin-2-yl)propanamide (8r), vol.1

2. and -. Ch,

, (m, 2H, -CH 2 -); 3.24-3.30 (m, 2H

1. Hz and A. , 16 (d, J ¼ 2.1 Hz, 1H, Ar-H), vol.7

, Ar-H); 7.79 (d, J ¼ 2.1 Hz, 1H, Ar-H), J References, vol.1, p.7

S. Chetty, M. Ramesh, A. S. Pillay, and M. E. Soliman, Bioorg. Med. Chem. Lett, vol.27, pp.370-386, 2017.

, Global tuberculosis report, 2016.

, Revised National Tuberculosis Control Program, Training manual on intensi?ed TB/HIV package, Ministry of Health and Family Welfare, 2017.

X. Lu, J. Tang, S. Cui, B. Wan, S. G. Franzblauc et al., Eur. J. Med. Chem, p.41, 2017.

, WHO Multidrug and extensively drug-resistant TB 2010 Global report on surveillance and response

H. Janmanchi, A. Raju, M. S. Degani, M. K. Ray, M. G. Rajan et al., , p.421, 2017.

A. H. Diacon, A. Pym, M. Grobusch, R. Patientia, R. Rustomjee et al., N. Engl. J. Med, p.2397, 2009.

N. Veziris, M. Ibrahim, N. Lounis, T. Andries, and V. Jarlier, PLoS One, 2011.

J. Cohen, Science, p.130, 2013.

A. H. Diacon, A. Pym, M. P. Grobusch, J. M. De-los-rios, E. Gotuzzo et al., N. Engl. J. Med, p.723, 2014.

S. Umamatheswari and C. Sankar, Bioorg. Med. Chem. Lett, p.695, 2017.

S. Jayaprakash, Y. Iso, B. Wan, S. G. Franzblau, and A. P. Kozikowski, ChemMedChem, 2006.

L. E. Bermudez, P. Kolonoski, M. Wu, P. A. Aralar, C. B. Inderlied et al., Antimicrob. Agents Chemother, p.1870, 1999.

L. E. Bermudez, P. Kolonoski, L. E. Seitz, M. Petrofsky, R. Reynolds et al., Antimicrob. Agents Chemother, p.3556, 2004.

L. E. Bermudez, P. Kolonoski, M. Petrofsky, M. Wu, C. B. Inderlied et al., J. Infect. Dis, vol.187, 1977.

J. Mao, H. Yuan, Y. Wang, B. Wan, D. Pak et al., Bioorg. Med. Chem. Lett, p.1263, 2010.

J. Mao, Y. Wang, B. Wan, A. P. Kozikowski, and S. G. Franzblau, ChemMedChem, 1624.

U. Sharma, P. Kumar, and B. Kumar, Mini-Rev. Med. Chem, p.678, 2010.

S. M. Capitosti, T. P. Hansen, and M. L. Brown, Bioorg. Med. Chem. Lett, p.327, 2004.

S. G. Stewart, C. J. Braun, S. L. Ng, M. E. Polomska, M. Karimi et al., Bioorg. Med. Chem, p.650, 2010.

S. H. Kok, R. Gambari, C. H. Chu, M. C. Yuen, E. Lin et al., Bioorg. Med. Chem, p.3626, 2008.

S. M. Sami, R. T. Dorr, D. S. Alberts, A. M. Solyom, and W. A. Remers, J. Med. Chem, p.3067, 2000.

R. Dahlbom, B. Karlen, R. George, and D. J. Jenden, J. Med. Chem, vol.9, pp.843-846, 1966.

H. Akgun, I. Karamelekoglu, B. Berk, I. Kurnaz, G. Saribiyik et al., Bioorg. Med. Chem, p.4149, 2012.

J. L. Santos, P. R. Yamasaki, C. M. Chin, C. H. Takashi, F. R. Pavan et al., Bioorg. Med. Chem. Lett, vol.17, p.15, 1923.

A. Rani, A. Viljoen, L. Sumanjit, V. Kremer, and C. Kumar, , 2017.

A. Singh, A. Viljoen, L. Kremer, V. Kumar-;-b, ). A. Singh et al., Chem. Biol. Drug Des, vol.9, p.856, 1701.

S. Kumar, A. Saini, J. Gut, P. J. Rosenthal, R. Raj et al., Eur. J. Med. Chem, p.993, 2017.

D. Di, F. M. Krogstad, L. D. Byers, and D. J. Krogstad, J. Med. Chem, p.4918, 1998.

V. K. Sambandamurthy, S. C. Derrick, T. Hsu, B. Chen, M. H. Larsen et al., Vaccine, p.6309, 2006.

J. Ollinger, M. A. Bailey, G. C. Moraski, A. Casey, S. Florio et al., PLoS One, issue.8, p.60531, 2013.