Sriram et al.
2-(2-(4-Bromo-2-fluorobenzyl)-1,2-dihydro-1-oxo
phthalazin-4-yl)-N-(5-nitrothiazol-2-yl)acetamide
(5n)
2-(2-(4-Bromo-2-fluorobenzyl)-4-(2-(4-(4-metho
xyphenyl)piperazin-1-yl)-2-oxoethyl)phthalazin-1
(2H)-one (5t)
1
1
Yield: 44%; m.p.: 171 ꢀC; H-NMR (DMSO-d6) d (ppm): 3.98 (s, 2H),
Yield: 89%; m.p.: 182 ꢀC; H-NMR (DMSO-d6) d (ppm): 2.54 (s, 4H),
5.33 (s, 2H), 6.8–8.19 (m, 7H), 8.6 (s, 1H); 12.0 (s, 1H); 13C NMR
(DMSO-d6) d (ppm): 186.8, 165.9, 161.7, 158.7, 145.3, 141.3, 135.6,
132.3, 131.2, 130.7, 129.8, 129.2, 127.6, 127.1, 122.7, 120.5, 38.9;
Anal: C20H13BrFN5O4S, C,H,N.
3.13 (t, 4H), 3.75 (s, 3H), 4.05 (s, 2H), 5.31 (s, 2H), 6.93–8.15 (m,
11H); 13C NMR (DMSO-d6) d (ppm): 186.8, 161.7, 158.7, 151.2,
142.5, 141.3, 132.3, 131.2, 130.7, 129.8, 129.2, 127.6, 127.1, 122.7,
120.5, 115.9, 115.2, 56.8, 50.6, 47.5, 38.9; Anal: C28H26BrFN4O3,
C,H,N.
2-(2-(4-Bromo-2-fluorobenzyl)-4-(2-(4-methylpi
perazin-1-yl)-2-oxoethyl)phthalazin-1(2H)-one
(5o)
2-(2-(4-Bromo-2-fluorobenzyl)-4-(2-(4-(3-methoxy
phenyl)piperazin-1-yl)-2-oxoethyl)phthalazin-1
(2H)-one (5u)
Yield: 61%; m.p.: 153 ꢀC; 1H-NMR (DMSO-d6) d (ppm): 2.54 (s,
4H), 3.13 (t, 4H), 3.75 (s, 3H), 4.05 (s, 2H), 5.31 (s, 2H), 6.93–8.15
(m, 11H); 13C NMR (DMSO-d6) d (ppm): 186.8, 162.5, 161.7, 158.7,
150.9, 141.3, 132.3, 131.2, 130.7, 129.8, 129.2, 127.6, 127.1,
122.7, 120.5, 103.2, 98.1, 50.6, 47.5, 38.9; Anal: C28H26BrFN4O3,
C,H,N.
1
Yield: 55%; m.p.: 133 ꢀC; H-NMR (DMSO-d6) d (ppm): 2.59 (t, 4H),
2.78 (s, 1H), 3.12 (t, 4H), 3.98 (s, 2H), 5.33 (s, 2H), 6.90–8.08 (m,
7H); 13C NMR (DMSO-d6) d (ppm): 186.8, 161.7, 158.7, 141.3, 132.3,
131.2, 130.7, 129.8, 129.2, 127.6, 127.1, 122.7, 120.5, 55.6, 47.6,
43.5, 38.9; Anal: C22H22BrFN4O2, C,H,N.
2-(2-(4-Bromo-2-fluorobenzyl)-4-(2-oxo-2-(4-phe
nylpiperazin-1-yl)phthalazin-1(2H)-one (5p)
2-(2-(4-Bromo-2-fluorobenzyl)-4-(2-(4-benzylpi
perazin-1-yl)-2-oxoethyl)phthalazin-1(2H)-one
(5v)
1
Yield: 80%; m.p.: 198 ꢀC; H-NMR (DMSO-d6) d (ppm): 2.55 (s, 4H),
3.12 (t, 4H), 4.01 (s, 2H), 5.32 (s, 2H), 6.94–8.18 (m, 12H); 13C NMR
(DMSO-d6) d (ppm): 186.8, 161.7, 158.7, 149.5, 141.3, 132.3, 131.2,
130.7, 129.8, 129.2, 127.6, 127.1, 122.7, 120.5, 118.6, 114.8, 50.6,
47.5, 38.9; Anal: C27H24BrFN4O2, C,H,N.
1
Yield: 52%; m.p.: 119 ꢀC; H-NMR (DMSO-d6) d (ppm): 3.96 (s, 2H),
4.14 (s, 2H), 5.33 (s, 2H), 7.17–8.19 (m, 12H); 13C NMR (DMSO-d6)
d (ppm): 186.8, 161.7, 158.7, 141.3, 135.4, 132.3, 131.2, 130.7,
129.8, 129.2, 128.9, 128.1, 127.6, 127.8, 127.1, 122.7, 120.5, 61.2,
50.6, 47.5, 38.9; Anal: C28H26BrFN4O2, C,H,N.
2-(2-(4-Bromo-2-fluorobenzyl)-4-(2-(4-(4-fluorop
henyl)piperazin-1-yl)-2-oxoethyl)phthalazin-1
(2H)-one (5q)
2-(4-Bromo-2-fluorobenzyl)-4-(2-oxo-2-(4-pyri
din-2-yl)piperazin-1-yl)ethyl)phthalazin-1(2H)-
one (5w)
1
Yield: 88%; m.p.: 191 ꢀC; H-NMR (DMSO-d6) d (ppm): 2.55 (s, 4H),
3.12 (t, 4H), 4.01 (s, 2H), 5.32 (s, 2H), 6.94–8.18 (m, 11H); 13C NMR
(DMSO-d6) d (ppm): 186.8, 161.7, 158.7, 152.2, 145.3, 141.3, 132.3,
131.2, 130.7, 129.8, 129.2, 127.6, 127.1, 122.7, 120.5, 116.5, 115.2,
50.6, 47.5, 38.9; Anal: C27H23BrF2N4O2, C,H,N.
1
Yield: 60%; m.p.: 131 ꢀC; H-NMR (DMSO-d6) d (ppm): 2.55 (s, 4H),
3.12 (t, 4H), 4.01 (s, 2H), 5.32 (s, 2H), 6.94–8.18 (m, 11H); 13C NMR
(DMSO-d6) d (ppm): 186.8, 161.7, 158.7, 154.3, 148.7, 141.3, 138.9,
132.3, 131.2, 130.7, 129.8, 129.2, 127.6, 127.1, 122.7, 120.5, 114.2,
50.6, 47.5, 38.9; Anal: C26H23BrFN5O2, C,H,N.
2-(2-(4-Bromo-2-fluorobenzyl)-4-(2-(4-(4-bromo
phenyl)piperazin-1-yl)-2-oxoethyl)phthalazin-1
(2H)-one (5r)
2-(4-Bromo-2-fluorobenzyl)-4-(2-oxo-2-(4-pipero
noyl)piperazin-1-yl)ethyl)phthalazin-1(2H)-one
(5x)
1
Yield: 82%; m.p.: 174 ꢀC; H-NMR (DMSO-d6) d (ppm): 2.54 (s, 4H),
3.13 (t, 4H), 4.05 (s, 2H), 5.31 (s, 2H), 6.93–8.15 (m, 11H); 13C NMR
(DMSO-d6) d (ppm): 186.8, 161.7, 158.7, 149.3, 141.3, 132.8, 132.3,
131.2, 130.7, 129.8, 129.2, 127.6, 127.1, 122.7, 120.5, 116.8, 112.5,
50.6, 47.5, 38.9; Anal: C27H23Br2FN4O2, C,H,N.
1
Yield: 88%; m.p.: 141 ꢀC; H-NMR (DMSO-d6) d (ppm): 2.55 (s, 4H),
3.12 (t, 4H), 4.01 (s, 2H), 5.32 (s, 2H), 6.12 (s, 2H), 7.12–8.18 (m,
10H); 13C NMR (DMSO-d6) d (ppm): 190.5, 186.8, 161.7, 158.7,
150.1, 148.4, 141.3, 132.3, 131.2, 130.7, 129.8, 129.2, 128.3, 127.6,
127.1, 122.7, 120.5, 115.3, 112.6, 101.3, 50.6, 47.5, 38.9; Anal:
C29H24BrFN4O5, C,H,N.
2-(2-(4-Bromo-2-fluorobenzyl)-4-(2-(4-(3-(trifluoro
methyl)phenyl)piperazin-1-yl)-2-oxoethyl)
phthalazin-1(2H)-one (5s)
1
Yield: 88%; m.p.: 208 ꢀC; H-NMR (DMSO-d6) d (ppm): 2.54 (s, 4H),
Antimycobacterial activity in log-phase
cultures
All compounds were screened for their in vitro antimycobacterial
activity against log-phase cultures of MTB, MDR-TB, and NTM spe-
cies like M. smegmatis ATCC 14468, M. microti MTCC 1727,
3.13 (t, 4H), 4.05 (s, 2H), 5.31 (s, 2H), 6.93–8.16 (m, 11H); 13C NMR
(DMSO-d6) d (ppm): 186.8, 161.7, 158.7, 150.5, 141.3, 132.3, 131.9,
131.2, 130.7, 129.8, 129.2, 127.6, 127.1, 124.2, 122.7, 120.5, 115.2,
110.4, 50.6, 47.5, 38.9; Anal: C28H23BrF4N4O2, C,H,N.
388
Chem Biol Drug Des 2010; 75: 381–391