Month 2015
Synthesis and in vitro Antimicrobial Activity of Nalidixic Acid Hydrazones
δ (ppm)=1.53–1.56 (t, 3H, CH3, J= 3Hz), 2.72 (s, 3H, CH3),
4.58–4.65 (q, 2H, CH2, J=6Hz, J=9Hz), 7.05–7.11 (m, 1H,
ArH), 7.24–7.25 (m, 2H, ArH), 7.34–7.37 (d, 1H, H6-
naphthyridine, J=9Hz), 8.49 (s, 1H, H2-naphthyridine),
8.66–8.68 (d, 1H, H5-naphthyridine, J = 6 Hz), 9.05 (s,
1H, N¼CH), 13.26 (s, 1H, CONH); 13C NMR (CDCl3) δ
(ppm) = 15.3, 25.3, 47.1, 111.9, 115.3, 120.9, 121.7,
125.6, 130.7, 135.2, 136.3, 141.3, 148.5 (N¼CH), 159.5,
161.6, 162.9, 163.7 (C¼O), 176.7 (C¼O). Analysis for
C19H16ClFN4O2 (386.81) Calculated: C: 59.00%, H:
4.17%, N: 14.48%; Found: C: 59.03%, H: 4.15%, N:
56.91%, H: 4.21%, N: 15.62%; Found: C: 56.87%, H:
4.19%, N: 15.64%.
1-Ethyl-7-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-
carboxylic acid [(1H-indol-3-yl)methylidene]-hydrazide
1
(15). Yield: 63%; m.p.: 206–208°C. H NMR (CDCl3)
δ (ppm)=1.49–1.51 (t, 3H, CH3, J=6Hz, J=9Hz), 2.68
(s, 3H, CH3), 4.47–4.54 (q, 2H, CH2, J=6Hz, J=9Hz),
7.20–7.26 (m, 5H, indole), 7.34–7.37 (d, 1H, H6-naphthyridine,
J = 9 Hz), 8.52 (s, 1H, H2-naphthyridine), 8.66–8.69
(d, 1H, H5-naphthyridine, J=9Hz), 8.67 (s, 1H, N¼CH),
9.07 (s, 1H, NH), 12.99 (s, 1H, CONH); 13C NMR
(CDCl3) δ (ppm)=15.2, 25.1, 46.4, 103.6, 105.7, 111.6,
113.2, 118.4, 119.3, 120.7, 121.2, 121.9, 127.12, 136.9,
137.3, 141.2, 146.6, 148.9 (N¼CH), 162.7, 166.3 (C¼O),
174.7 (C¼O). Analysis for C21H19N5O2 (373.41) Calculated:
C: 67.55%, H: 5.13%, N: 18.76%; Found: C: 67.64%, H:
14.51%.
1-Ethyl-7-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-
carboxylic acid (2,3-difluoro-benzylidene)-hydrazide (12). Yield:
71%; m.p.: 258–260°C. 1H NMR (CDCl3) δ (ppm)
=1.52–1.57 (t, 3H, CH3, J=9Hz, J=6 Hz), 2.71 (s, 3H,
CH3), 4.58–4.65 (q, 2H, CH2, J=6Hz), 7.10–7.19 (m, 1H,
ArH), 7.34–7.37 (d, 1H, H6-naphthyridine, J = 9 Hz),
7.85–7.90 (m, 1H, ArH), 7.93–7.99 (m, 1H, ArH), 8.48
(s, 1H, H2-naphthyridine), 8.65–8.68 (d, 1H, H5-
naphthyridine, J = 9 Hz), 9.02 (s, 1H, N¼CH), 13.32 (s,
1H, CONH); 13C NMR (CDCl3) δ (ppm) = 15.3, 25.3,
47.2, 111.8, 118.5, 120.1, 121.7, 122.2, 122.5, 124.1,
124.2, 136.3, 140.1, 147.1, 148.5 (N¼CH), 155.1, 161.8,
163.8 (C¼O), 176.7 (C¼O). Analysis for C19H16F2N4O2
(370.35) Calculated: C: 61.62%, H: 4.35%, N: 15.13%;
5.10%, N: 18.73%.
1-Ethyl-7-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-
carboxylic acid [(6-chloro-benzo[1,3]dioxol-5-yl)methylidene]-
1
hydrazide (16). Yield: 69%; m.p.: 254–256°C. H NMR
(CDCl3) δ (ppm)=1.54–1.58 (t, 3H, CH3, J=6Hz), 2.72
(s, 3H, CH3), 4.38–4.44 (q, 2H, CH2, J = 6 Hz), 4.68
(s, 2H, CH2), 6.84 (s, 1H, ArH), 6.92 (s, 1H, ArH),
7.36–7.39 (d, 1H, H6-naphthyridine, J = 9 Hz), 7.75
(s, 1H, H2-naphthyridine), 8.67–8.70 (d, 1H, H5-
naphthyridine, J=9Hz), 8.95 (s, 1H, N¼CH), 12.90 (s,
1H, CONH); 13C NMR (CDCl3) δ (ppm)=12.4, 24.3,
45.8, 87.4, 103.2, 107.4, 108.6, 119.3, 121.9, 127.1, 128.1,
137.3, 146.6, 149.4 (N¼CH), 149.9, 153.3, 159.9, 160.7,
161.8 (C¼O), 180.2 (C¼O). Analysis for C20H17ClN4O4
(412.83) Calculated: C: 58.19%, H: 4.15%, N: 13.57%;
Found: C: 58.23%, H: 4.11%, N: 13.52%.
Found: C: 61.66%, H: 4.31%, N: 15.11%.
1-Ethyl-7-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-
carboxylic acid [(1H-pyrrol-2-yl)methylidene]-hydrazide (13).
Yield: 23%; m.p.: 252–254°C. 1H NMR (CDCl3) δ (ppm)
=1.54–1.56 (t, 3H, CH3, J=3Hz), 2.73 (s, 3H, CH3),
4.60–4.64 (q, 2H, CH2, J=3Hz, J=6Hz), 6.26–6.28 (m,
1H, pyrrole), 6.51–6.52 (m, 1H, pyrrole), 6.96 (s, 1H,
pyrrole), 7.35–7.36 (d, 1H, H6-naphthyridine, J=3Hz),
8.07 (s, 1H, H2-naphthyridine), 8.67–8.69 (d, 1H, H5-
naphthyridine, J=6Hz), 9.01 (s, 1H, N¼CH), 12.42 (s,
1H, CONH); 13C NMR (CDCl3) δ (ppm)=12.4, 24.3,
45.8, 103.8, 110.8, 116.2, 119.3, 119.5, 121.9, 124.7,
136.9 (N¼CH), 137.3, 153.3, 159.9, 160.7, 161.8 (C¼O),
180.1 (C¼O). Analysis for C17H17N5O2 (323.35)
Calculated: C: 63.15%, H: 5.30%, N: 21.66%; Found: C:
Microbiology
In vitro antimicrobial assay. The examined compounds
3–16 were in vitro screened for antibacterial and antifungal
activities using the broth microdilution method according
to both the European Committee on Antimicrobial
Susceptibility Testing [19] and the Clinical and Laboratory
Standards Institute guidelines [20] against a panel of reference
and clinical or saprophytic strains of microorganisms,
including Gram-positive bacteria (Staphylococcus aureus
ATCC 25923, S. aureus ATCC 43300, S. aureus ATCC
6538, Staphylococcus epidermidis ATCC 12228, Bacillus
subtilis ATCC 6633, Bacillus cereus ATCC 10876,
Micrococcus luteus ATCC 10240), Gram-negative bacteria
(Escherichia coli ATCC 25922, Klebsiella pneumoniae
ATCC 13883, Proteus mirabilis ATCC 12453, Bordetella
bronchiseptica ATCC 4617, Salmonella typhimurium
ATCC 14028, Pseudomonas aeruginosa ATCC 9027) and
fungi belonging to yeasts (Candida albicans ATCC 2091,
C.albicans ATCC 10231, Candida parapsilosis ATCC
22019) and molds (Aspergillus niger ATCC 16404,
Aspergillus fumigatus, Penicillium spp., and Rhizopus
spp.). The microorganisms belonging to ATCC came from
the American Type Culture Collection, routinely used for
63.18%, H: 5.25%, N: 21.69%.
1-Ethyl-7-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-
carboxylic acid [(5-chlorofuran-2-yl)methylidene]-hydrazide (14).
1
Yield: 72%; m.p.: 202–204°C. H NMR (CDCl3) δ (ppm)
=1.50–1.55 (t, 3H, CH3, J=9Hz, J=6Hz), 2.70 (s, 3H,
CH3), 4.56–4.63 (q, 2H, CH2, J=6Hz), 6.27–6.28 (d, 1H,
furan, J=3Hz), 6.83–6.84 (d, 1H, furan, J=3Hz), 7.32–
7.34 (d, 1H, H6-naphthyridine, J = 6 Hz), 8.41 (s, 1H,
H2-naphthyridine), 8.65–8.69 (d, 1H, H5-naphthyridine,
J=12Hz), 9.02 (s, 1H, N¼CH), 13.17 (s, 1H, CONH); 13
C
NMR (CDCl3) δ (ppm)=15.3, 25.3, 47.2, 108.9, 109.4,
121.5, 131.3, 136.8, 139.1, 141.2, 146.2, 148.7, 149.1
(N¼CH), 161.6, 163.7, 163.7 (C¼O), 176.6 (C¼O).
Analysis for C17H15ClN4O3 (358.78) Calculated: C:
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet