Med Chem Res (2011) 20:1–8
7
groups. The absorption at 3476–3286, 2210, and
1630–1651 cm-1 are characteristic of m(NH2), m(CN), and
m(CH=N), respectively (Table 1).
most synthesized compounds, except for 2a and 2h, show
biological activity against P. aeruginosa.
The ring size of cycloalkanes and nature of the sub-
stituent at the C4-position of pyridine do not present clear
information about the SAR. However, 5-methyl thiophene
at C4 exhibits respectable antimicrobial activity against
P. aeruginosa ATCC 29212 (Table 2).
Structures of 2-amino-3-cyanopyridines were identified
1
primarily with H- and 13C-HMR spectra. While aliphatic
proton and aromatic proton signals showed d 1.40–3.00 ppm
and d 6.10–7.40 ppm, respectively, the 1H-NMR spectra of
amine protons appeared at a characteristic signal of d
5.00 ppm. The 13C-NMR spectral data on synthesized
compounds are also in accordance with the proposed
structures.
Conclusion
Synthesized compounds were evaluated for their in vitro
antibacterial and antifungal activity (Table 2). Compounds
2a, 2c, 2d, 2f, and 2g showed antimicrobial activity against
Bacillus subtilis RSKK 244. 2-Amino-6,7-dihydro-4-(5-
methylfuran-2-yl)-5H-cyclopenta[b]pyridine-3-carbonitrile
(2g) has more activity than ampicillin against Bacillus
subtilis RSKK 244.
In this study, nine new aminocycanoprydine derivatives
1
were synthesized and characterized by FT-IR, H-NMR,
13C-NMR, and CHN analysis. Their antibiogram tests
showed better results than some known antibiotics. In
general, 2-amino-3-cyanaopyridines substituted at C4 with
5-methyl furan and thiophene show better activity than
3-methyl thiophene-substituted compounds. However,
except against P. aeruginosa, six-member cycloalkane-
fused compounds did not show good results compared to
five- and seven-member compounds.
Compounds 2c, 2f, and 2g, and especially 2-amino-
5,6,7,8-tetrahydro-4-(5-methylthiophen-2-yl)quinoline-3-
carbonitrile (2e), show more activity than gentamicin
against Pseudomonas aeruginosa ATCC 29212. All of the
compounds, except 2c, have average antimicrobial activity
against Micrococcus luteus NRRLB 4375. 2-Amino-
6,7,8,9-tetrahydro-4-(5-methylthiophen-2-yl)-5H-cyclohepta-
[b]pyridine-3-carbonitrile (2f) possesses the best activity
against Micrococcus luteus NRRLB 4375 compared with
the other compounds. Unfortunately, none of the synthe-
sized 2-amino-3-cyanopyridines derivatives showed any
activity against Bacillus megaterium or Candida albicans
(ATCC 90028). The MICs of ketoconazole, ampicillin,
tetracycline, penicillin, and gentamicin were determined
individually in parallel experiments in order to control the
sensitivity of the test organisms. MIC values of the com-
pounds and the standards are presented in Table 3.
As reported in Table 2, the six-membered cycloalkane
fused with 2-amino-3-cyanopyridenes (2b, 2e, 2h),
regardless of the nature of the heterocyclic and methyl
substituent at the 3- or 5-position, did not show any bio-
logical activity against B. subtilis. In the seven-membered
fused system (2f, 2c), we observed the same activity
against B. subtilis. The position of the methyl group at the
thiophene ring was not significant. Moreover, the furan
derivative (2i) did not show any activiy. The best result
was obtained in the case of the five-membered cycloalkane
(2g) along with 5-methyl furan. As shown above, the
biological activity against B. subtilis is dependent on the
ring size and substituent.
Acknowledgments The authors thank the Gazi University Scientific
Research Fund (Project no. 05/2008-47) for financial support. We also
thank Mu¨nteha N. Sonuc and Refiye Tekiner for their help with
carrying out antibacterial studies.
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