Nalidixic Acid-Based 1,3,4-Oxa(thia)diazoles as Antibacterial Agents
112.07, 119.17, 121.54, 125.87, 131.51 (2C), 133.59, 136.07, 139.92,
thyridine); IR (KBr, per cm) mmax: 3322, 2928, 1608, 1574, 1441,
1316, 1246, 788; MS calculated for C21H18F3N5OS2: 477.0905;
Observed MS-ES (m ⁄ z): 477.18 (M+).
148.17, 152.60, 167.76, 173.71, 175.82; IR (KBr, per cm) mmax: 3225,
2979, 1607, 1545, 1462, 1430, 1384, 1251, 792; MS calculated for
C20H18ClN5OS2: 443.0641; Observed MS-ES (m ⁄ z): 443.23 (M+),
445.19.
3-(4-((4-Acetylphenylamino)methyl)-5-thioxo-
4,5-dihydro-1,3,4-thiadiazol-2-yl)-1-ethyl-7-
methyl-1,8-naphthyridin-4(1H)-one (33)
3-{4-[(4-Bromo-phenylamino)-methyl]-5-thioxo-
4,5-dihydro-1,3,4-thiadiazol-2-yl}-1-ethyl-7-
methyl-1H-1,8-naphthyridin-4-one (29)
1
Yellow solid; M.p.: 207 ꢀC; Yield: 65%; H NMR (d): 1.57 (t, 3H, N-
CH2CH3), 2.65 (s, 3H, COCH3), 2.73 (s, 3H, 7-CH3), 4.75 (q, 2H, N-
CH2), 5.82 (s, 2H, NH-CH2), 6.43 (s, 1H, NH), 7.00 (d, J = 8.0 Hz,
2H, Ar-H), 7.32 (d, J = 8.4 Hz, 1H, H-6-naphthyridine), 7.37 (d,
J = 7.6 Hz, 2H, Ar-H), 8.61 (d, J = 8.0 Hz, 1H, H-5-naphthyridine),
9.12 (s, 1H, H-2-naphthyridine); 13C NMR (d): 15.51, 25.85, 29.71,
47.24, 59.69, 111.66, 113.20 (2C), 119.16, 120.30, 120.57, 121.54,
129.39 (2C), 136.12, 142.46, 145.32, 151.84, 154.70, 163.38, 174.28,
186.67; IR (KBr, per cm) mmax: 3345, 2985, 1667, 1620, 1544, 1441,
1340, 1252, 789; MS calculated for C22H21N5O2S2: 451.1137;
Observed MS-ES (m ⁄ z): 451.28 (M+).
1
Yellow solid; M.p.: 240 ꢀC (charring); Yield: 65%; H NMR (d): 1.55
(t, 3H, N-CH2CH3), 2.70 (s, 3H, 7-CH3), 4.62 (q, 2H, N-CH2), 5.72 (s,
2H, NH-CH2), 6.20 (s, 1H, NH), 6.80 (d, J = 8.8 Hz, 2H, Ar-H), 7.32
(d, J = 8.0 Hz, 1H, H-6-naphthyridine), 7.42 (d, J = 7.6 Hz, 2H, Ar-
H), 8.60 (d, J = 8.4 Hz, 1H, H-5-naphthyridine), 8.73 (s, 1H, H-2-
naphthyridine); IR (KBr, per cm) mmax: 3340, 2955, 1615, 1575, 1488,
1436, 1357, 1218, 787; MS calculated for C20H18BrN5OS2: 487.0136;
Observed MS-ES (m ⁄ z): 487.51 (M+), 489.42.
1-Ethyl-7-methyl-3-{4-[(4-nitro-phenylamino)-
methyl]-5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-
yl}-1H-1,8-naphthyridin-4-one (30)
3-(4-((4-Aminophenylamino)methyl)-5-thioxo-
4,5-dihydro-1,3,4-thiadiazol-2-yl)-1-ethyl-7-
methyl-1,8-naphthyridin-4(1H)-one (34)
1
Yellow solid; M.p.: 265 ꢀC (charring); Yield: 65%; H NMR (d): 1.57
1
(t, 3H, N-CH2CH3), 2.72 (s, 3H, 7-CH3), 4.65 (q, 2H, N-CH2), 5.81 (s,
2H, NH-CH2), 6.64 (s, 1H, NH), 6.99 (d, J = 9.0 Hz, 2H, Ar-H), 7.30
(d, J = 8.4 Hz, 1H, H-6-naphthyridine), 8.09 (d, J = 8.0 Hz, 2H, Ar-
H), 8.69 (d, J = 8.0 Hz, 1H, H-5-naphthyridine), 8.96 (s, 1H, H-2-
naphthyridine); IR (KBr, per cm) mmax: 3250, 2942, 1617, 1601, 1445,
1436, 1362, 1245, 796; MS calculated for C20H18N6O3S2: 454.0882;
Observed MS-ES (m ⁄ z): 455.28 (M+ + 1).
Yellow solid; M.p.: 268 ꢀC; Yield: 66%; H NMR (d): 1.55 (t, 3H, N-
CH2CH3), 2.68 (s, 3H, 7-CH3), 4.60 (q, 2H, N-CH2), 5.66 (s, 2H, NH2),
5.68 (s, 2H, NH-CH2), 6.17 (s, 1H, NH), 6.95 (d, J = 8.4 Hz, 2H, Ar-H),
7.28 (d, J = 8.4 Hz, 1H, H-6-naphthyridine), 7.14 (d, J = 8.0 Hz, 2H,
Ar-H), 8.58 (d, J = 8.0 Hz, 1H, H-5-naphthyridine), 8.74 (s, 1H, H-2-
naphthyridine); 13C NMR (d): 15.45, 25.29, 47.19, 60.18, 112.54,
114.44, 115.52, 116.94 (2C), 117.17 (2C), 121.73, 129.02, 136.02,
136.19, 141.15, 141.86, 148.21, 163.61, 186.65; IR (KBr, per cm) mmax
:
3363, 3238, 2920, 1620, 1583, 1548, 1440, 1347, 1232, 788; MS calcu-
1-Ethyl-7-methyl-3-{4-[(4-cyano-phenylamino)-
methyl]-5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-
yl}-1H-1,8-naphthyridin-4-one (31)
lated for C20H20N6OS2: 424.1140; Observed MS-ES (m ⁄ z): 424.84 (M+).
1
Yellow solid; M.p.: 278 ꢀC; Yield: 66%; H NMR (d): 1.56 (t, 3H, N-
3-(4-((3-Chloro-4-fluorophenylamino)methyl)-5-
thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)-1-ethyl-
7-methyl-1,8-naphthyridin-4(1H)-one (35)
CH2CH3), 2.72 (s, 3H, 7-CH3), 4.63 (q, 2H, N-CH2), 5.77 (s, 2H, NH-
CH2), 6.22 (s, 1H, NH), 7.01 (d, J = 8.4 Hz, 2H, Ar-H), 7.48 (d,
J = 8.4 Hz, 1H, H-6-naphthyridine), 8.60 (d, J = 7.6 Hz, 2H, Ar-H),
8.76 (d, J = 8.4 Hz, 1H, H-5-naphthyridine), 8.84 (s, 1H, H-2-naph-
thyridine); 13C NMR (d): 15.23, 25.12, 47.25, 58.44, 111.07, 113.29
(2C), 114.48, 118.93, 121.94, 129.24, 133.59 (2C), 135.96, 141.44,
148.09, 148.85, 152.54, 163.73, 163.91, 174.33; IR (KBr, per cm)
mmax: 3340, 2955, 1615, 1575, 1488, 1436, 1357, 1218, 787; MS cal-
culated for C21H18N6OS2: 434.0984; Observed MS-ES (m ⁄ z): 434.26
(M+).
Yellow solid; M.p.: 272 ꢀC; Yield: 69%; 1H NMR (d): 1.47 (t, 3H,
N-CH2CH3), 2.53 (s, 3H, 7-CH3), 4.66 (q, 2H, N-CH2), 5.64 (s, 2H, NH-
CH2), 5.88 (s, 1H, NH), 6.98 (s, 1H, Ar-H), 7.39 (d, J = 8.4 Hz, 1H, H-6-
naphthyridine), 7.42 (d, J = 8.4 Hz, 1H, Ar-H), 8.08 (d, J = 6.8 Hz, 1H,
Ar-H), 8.38 (d, J = 8.4 Hz, 1H, H-5-naphthyridine), 8.52 (s, 1H, H-2-
naphthyridine); IR (KBr, per cm) mmax: 3287, 3097, 1610, 1575, 1441,
1364, 1253, 789; MS calculated for C20H17ClFN5OS2: 461.0547;
Observed MS-ES (m ⁄ z): 461.10 (M+), 463.25.
1-Ethyl-7-methyl-3-(5-thioxo-4-((4-
(trifluoromethyl)phenylamino)methyl)-4,5-
dihydro-1,3,4-thiadiazol-2-yl)-1,8-naphthyridin-
4(1H)-one (32)
3-(4-[(2,4-Dinitrophenylamino)methyl]-5-thioxo-
4,5-dihydro-1,3,4-thiadiazol-2-yl)-1-ethyl-7-
methyl-1,8-naphthyridin-4(1H)-one (36)
1
Yellow solid; M.p.: 270 ꢀC; Yield: 66%; H NMR (d): 1.52 (t, 3H, N-
1
Yellow solid; M.p.: 215 ꢀC; Yield: 66%; H NMR (d): 1.53 (t, 3H, N-
CH2CH3), 2.68 (s, 3H, 7-CH3), 4.65 (q, 2H, N-CH2), 5.89 (s, 2H, NH-
CH2), 6.21 (s, 1H, NH), 7.38 (d, J = 8.4 Hz, 1H, H-6-naphthyridine),
7.74 (d, J = 6.8 Hz, 1H, Ar-H), 8.28 (d, J = 7.2 Hz, 1H, Ar-H), 8.76
(d, J = 8.0 Hz, 1H, H-5-naphthyridine), 8.87 (s, 1H, Ar-H), 9.26 (s,
1H, H-2-naphthyridine); IR (KBr, per cm) mmax: 3241, 2976, 1604,
CH2CH3), 2.69 (s, 3H, 7-CH3), 4.61 (q, 2H, N-CH2), 5.77 (s, 2H, NH-
CH2), 6.28 (s, 1H, NH), 7.02 (d, J = 8.4 Hz, 2H, Ar-H), 7.43 (d,
J = 8.8 Hz, 2H, Ar-H), 7.32 (d, J = 8.4 Hz, 1H, H-6-naphthyridine),
8.58 (d, J = 8.4 Hz, 1H, H-5-naphthyridine), 8.69 (s, 1H, H-2-naph-
Chem Biol Drug Des 2012; 79: 384–397
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