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6’’), 130.1 (C-4’’), 132.1 (C-3’ and C-5’), 134.3 (C-1’’) 136.3 (C-4 or
C-5), 138.4 (C-4 or C-5), 145.4 (C-1’), 148.2 (N@CH), 156.9 (C@O)
ppm. Anal. Calcd for C17H15BrN6O: C, 51.14; H, 3.79; N, 21.05.
Found: C, 51.10; H, 4.00; N, 20.41.
4.1.7. 1-(4’-Fluorophenylamino)-N0-[(fur-200-yl)methylene]-5-
methyl-1H-1,2,3-triazole-4-carbohydrazide 8m
Compound 8m obtained as a white solid by condensation of 10d
with 2-furaldehyde. IR (KBr) mmax (cmꢀ1) 3297 and 3195 (N–H);
1645 (C@O); 1607 (C@N); 1H NMR (300.00 MHz, DMSO-d6) d
2.47 (s, 3H, CH3), 6.54 (d, 2H, J = 8.8; 4.4, H-2’ and H-6’), 6.64 (dd,
1H, J = 3.4; 1.7, H-3’’), 6.90 (d, 1H, J = 3.4, H-2’’), 7.10 (d, 2H,
J = 9,0; 8.8, H-3’ and H-5’), 7.85 (d, 1H, J = 1.7, H-4’’), 8.46 (s, 1H,
N@CH), 10.20 (br s, 1H, N–H), 12.14 (br s, 1H, NH–N) ppm. 13C
NMR (75 MHz, DMSO-d6) d 8.1 (CH3), 112.1 (C-3’’), 113.2 (C-2’’),
114.6 (J = 7.7, C-2’ and C-6’), 115.9 (J = 23.2, C-3’and C-5’), 136.2
(C-4 or C-5), 137.8 (N@CH), 137.8 (C-4’’), 138.3 (C-4 or C-5),
142.5 (J = 1.7, C-1’), 149.5 (C-1’’), 156.8 (C@O), 157.2 (J = 236.9, C-
4’) ppm. Anal. Calcd for C15H13FN6O2: C, 54.88; H, 3.99; N, 25.60.
Found: C, 54.91; H, 3.99; N, 25.48.
4.1.3. 1-(4’’-Fluorophenylamino)-5-methyl-N0-(phenylmethyle
ne)-1H-[1,2,3]-triazole-4-carbohydrazide 8d
Compound 8d obtained as a white solid by condensation of 10d
with benzaldehyde. IR (KBr) mmax (cmꢀ1) 3304 and 3054 (N–H);
1676 (C@O); 1592 (C@N) 1H NMR (300.00 MHz, DMSO-d6) d 2.48
(s, 3H, CH3), 6.54 (dd, 2H, J = 8.8; 4.4, H-2’ and H-6’), 7.11 (dd,
2H, J = 8.8; 4.4, H-3’ and H-5’), 7.45–7.47 (m, 3H, H-2’’, H-4’’ and
H-6’’), 7.68–7.75 (m, 2H, H-3’’ and H-5’’), 8.58 (s, 1H, N@CH),
10.36 (br s, 1H, N–H), 12.10 (br s, 1H, NH –N) ppm. 13C NMR
(75 MHz, DMSO-d6) d 8.1 (CH3), 114.6 (J = 8.5, C-2’ e C-6’), 116.0
(J = 22.6, C-3’ and C-5’), 127.0 (C-3’’ and C-5’’), 128.8 (C-2’’ and C-
6’’), 130.0 (C-4’’), 134.3 (C-1’’), 136.2 (C-4 or C-5), 138.3 (C-4 or
C-5), 142.6 (J = 2.3, C-1’), 148.1 (N@CH), 157.0 (C@O) ppm. Anal.
Calcd for C17H15FN6O: C, 60.35; H, 4.47; N, 24.84. Found: C,
58.13; H, 4.69; N, 24.13.
4.1.8. General procedure for the preparation of the N-substitu
ted-phenyltriazolyl-4-acylhydrazone derivatives 8p–q
A solution of 5-nitro-2-furfurylidene diacetate (0.4 mmol) in a
mixture of EtOH (10.0 mL) with a 50% aqueous solution of sulfuric
acid (1.0 mL) was heated for 1–2 min on a steam bath and cooled
to room temperature. Compounds 10c–d (0.4 mmol) were then
added and the resulting mixture was stirred for two hours at room
temperature after which it was poured into crushed ice. The insol-
uble product was filtered off and then purified by column chroma-
tography using a 1:1 n-hexane/EtOAc mixture as the eluent.
4.1.4. N0-[(500-Bromothien-200-yl)methylene]-1-(4’-bromopheny
lamino)-5-methyl-1H-[1,2,3]-triazole-4-carbohydrazide 8g
Compound 8g obtained as a white solid by condensation of 10c
with 2-bromothiophene-5-carboxaldehyde. IR (KBr) mmax (cmꢀ1
)
3298 and 3165 (N–H); 1640 (C@O); 1602 (C@N) 1H NMR
(300.00 MHz, DMSO-d6) d 2.45 (s, 3H, CH3), 6.46 (d, 2H, J = 8.8, H-
2’ and H-6’), 7.27 (d, 1H, J = 0.7, H-2’’), 7.27 (d, 1H, J = 0.7, H-3’’),
7.42 (d, 2H, J = 8.8, H-3’ and H-5’), 8.66 (s, 1H, N@CH), 10.38 (br
s, 1H, N–H), 12.23 (br s, 1H, NH –N) ppm. 13C NMR (75 MHz,
DMSO-d6) d 8.4 (CH3), 113.3 (C-4’), 115.3 (C-4’’), 115.4 (C-2’ and
C-6’), 131.7 (C-2’’), 131.9 (C-3’’), 132.6 (C-3’ and C-5’), 136.4 (C-4
or C-5), 139.1 (C-4 or C-5), 141.1 (C-1’’), 142.9 (N=CH), 145.6 (C-
1’), 157.4 (C@O) ppm. Anal. Calcd for C15H12Br2N6OS: C, 37.21; H,
2.50; N, 17.36. Found: C, 37.68; H, 3.01; N, 16.81.
4.1.9. N’-[(500-Nitrofur-200-yl)methylene]-1-(4’-bromophenylam
ino)-5-methyl-1H-1,2,3-triazole-4-carbohydrazide 8p
Compound 8p obtained as a yellow by condensation of 10c with
5-nitrofuraldehyde. IR (KBr) mmax (cmꢀ1) 3435 and 3267 (N–H);
1637 (C@O); 1613 (C@N) 1H NMR (300.00 MHz, DMSO-d6) d 2.47
(s, 3H, CH3), 6.48 (d, 2H, J = 8.8, H-2’ and H-6’), 7.25 (d, 1H,
J = 4.1, H-3’’), 7.43 (d, 2H, J = 8.8, H-3’ and H-5’), 7.78 (d, 1H,
J = 3.9, H-2’’), 8.53 (s, 1H, N@CH), 10.38 (br s, 1H, N–H) ppm. 13C
NMR (75 MHz, DMSO-d6) d 8.1 (CH3), 112.8 (C-4’), 114.6 (C-2’’),
114.9 (C-3’’), 115.1 (C-2’ and C-6’), 132.1 (C-3’ and C-5’), 135.8
(N@CH), 135.9 (C-4 or C-5), 139.0 (C-4 or C-5), 145.2 (C-1’),
145.3 (C-1’’), 151.8 (C-4’’), 157.1 (C@O) ppm. Anal. Calcd for
4.1.5. N0-[(500-Bromothien-200-yl)methylene]-1-(4’-fluoropheny
lamino)-5-methyl-1H-[1,2,3]-triazole-4-carbohydrazide 8h
Compound 8h obtained as a white solid by condensation of 10d
with 2-bromothiophene-5-carboxaldehyde. IR (KBr) mmax (cmꢀ1
)
C15H12BrN7O4: C, 41.49; H, 2.79; N, 22.58. Found: C, 41.10; H,
3439 and 3292 (N–H); 1664 (C@O); 1601 (C@N); 1H NMR
(300.00 MHz, DMSO-d6) d 2.46 (s, 3H, CH3), 6.56 (d, 2H, J = 8.8;
4.5, H-2’ and H-6’), 7.10 (dd, 2H, J = 8.8; 4.5 H-3’ and H-5’), 7.27
(m, 2H, H-2’’ and H-3’’), 8.66 (s, 1H, N@CH), 10.17 (br s, 1H, N–
H), 12.17 (br s, 1H, NH–N) ppm. 13C NMR (75 MHz, DMSO-d6) d
8.0 (CH3), 114.6 (C-4’’), 114.7 (J = 7.7, C-2’ and C-6’), 115.9
(J = 23.2, C-3’ and C-5’), 131.1 (C-200), 131.2 (C-300), 136.1 (C-4 or
C-5), 138.3 (C-4 or C-5), 141.0 (C-100), 142.1 (N@CH), 142.4 (C-4’),
156.8 (C@O) ppm. Anal. Calcd for C15H12BrFN6OS: C, 42.56; H,
2.86; N, 19.86. Found: C, 42.13; H, 2.79; N, 18.63.
2.50; N, 18.20.
4.1.10. N’-[(500-Nitrofur-200-yl)methylene]-1-(4’-fluorophenylam
ino)-5-methyl-1H-1,2,3-triazole-4-carbohydrazide 8q
Compound 8q obtained as a yellow by condensation of 10d with
5-nitrofuraldehyde. IR (KBr) m
max (cmꢀ1) 3200 (N–H); 1664 (C@O);
1589 (C@N); 1H NMR (300.00 MHz, DMSO-d6) d 2.48 (s, 3H, CH3),
6.58 (d, 2H, J = 9.0, H-2’ and H-6’), 7.10 (d, 2H, J = 9.0, H-3’ and
H-5’), 7.25 (d, 1H, J = 3.8, H-2’’), 7.78 (d, 2H, J = 3.8, H-3’’), 8.53 (s,
1H, N@CH), 10.21, (br s, 1H, N–H), 12.59 (br s, 1H, NH–N) ppm.
13C NMR (75 MHz, DMSO-d6) d 8.2 (CH3), 114.6 (C-2’’), 114.7
(J = 7.7, C-2’ and C-6’), 115.0 (C-3’’), 116.0 (J = 22,6, C-3’ and C-5’),
135.7 (N@CH), 135.8 (C-4 or C-5), 138.9 (C-4 or C-5), 142.5
(J = 1.7, C-1’), 151.8 (C-1’’), 151.8 (C-4’’), 157.2 (C@O), 157.3
(J = 237.5, C-4’) ppm. Anal. Calcd for C15H12FN7O4: C, 48.26; H,
3.24; N, 26.27. Found: C, 48.10; H, 3.10; N, 26.20.
4.1.6. 1-(4’-Bromophenylamino)-N0-[(fur-200-yl)methylene]-5-
methyl-1H-1,2,3-triazole-4-carbohydrazide 8l
Compound 8l obtained as a white solid by condensation of 10c
with 2-furaldehyde. IR (KBr) mmax (cmꢀ1) 3437 and 3220 (N–H);
1671 (C@O); 1589 (C@N); 1H NMR (300.00 MHz, DMSO-d6) d
2.46 (s, 3H, CH3), 6.47 (d, 2H, J = 8.8, H-2’ and H-6’), 6.63 (dd, 1H,
J = 2.9; 1.7, H-3’’), 6.90 (d, 1H, J = 2.9, H-2’’), 7.42 (d, 2H, J = 8.8,
H-3’ and H-5’), 7.85 (d, 1H, J = 1.7, H-4’’), 8.46 (s, 1H, N@CH),
10.39 (br s, 1H, N–H), 12.15 (br s, 1H, NH –N) ppm. 13C NMR
(75 MHz, DMSO-d6) d 8.3 (CH3), 112.4 (C-3’’), 113.1 (C-4’), 113.8
(C-2’’), 115.2 (C-2’ and C-6’), 132.3 (C-3’ and C-5’), 136.4 (C-4 or
C-5), 138.2 (N@CH), 138.2 (C-4’’), 138.7 (C-4 or C-5), 145.6 (C-1’),
149.6 (C-1’’), 157.6 (C@O) ppm. Anal. Calcd for C15H13BrN6O2: C,
46.29; H, 3.37; N, 21.59. Found: C, 46.59; H, 3.91; N, 20.69.
4.2. Pharmacology
4.2.1. In vitro evaluation of antitubercular activity
The drug potency was determined by the Microplate Alamar
Blue assay (MABA), which shows good correlation and proportion-
ality with the BACTEC MGIT 960 method. This colorimetric method
uses the Alamar Blue–resazurin-based oxidation–reduction indica-
tor to obtain drug susceptibility measurements for bacteria.