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compound 7 with equivalent of methyl or ethyl cyanoacetate in
EtOH in the presence of NH4OH according to known method10 with
minor modification. When equivalent amount of compound 8a and
appropriate arylamines were mixed in EtOH and refluxed for 5 h,
compounds 4a–c were formed. Compounds 4d–m were prepared
by cyclization of compound 8b with arylamines in EtOH.
In conclusion, alkyl-2-(7-chloro-5,8-dioxo-5,8-dihydroquino-
lin-6-yl)-2-cyanoacetate (8a or 8b) was synthesized by nucleo-
philic substitution of compound
7 with equivalent of alkyl
cyanoacetate in the presence of NH4OH. The compound 10 was
prepared by nucleophilic substitution of 2,3-dichloro-1,4-naphtho-
quinone (9) with equivalent of malononitrile in the presence of
triethylamine. 1H-Pyrrolo[3,2-g]quinoline-4,9-diones 4a–m and
4,9-dioxo-4,9-dihydro-1H-benzo[f]indoles 5a–e were synthesized
by cyclization of compounds 8a, 8b, or 10 with amines in EtOH.
Among them tested, many of compounds 4a–m and 5a–e showed
potent antifungal activity against pathogenic fungi. These 1H-pyr-
rolo[3,2-g]quinoline-4,9-diones and 4,9-dioxo-4,9-dihydro-1H-
benzo[f]indoles may thus be promising leads for the development
of antifungal agents. Moreover, the results should encourage the
synthesis of these analogs for improving antifungal properties.
In similar manner, a method for the synthesis of 2-amino-1-alkyl
or aryl-4,9-dioxo-4,9-dihydro-1H-benzo[f]indole-3-carbonitriles
5a–e is shown in Scheme 1 and Table 1. The 2-(3-chloro-1,4-
dioxo-1,4-dihydro-naphthalen-2-yl)-malononitrile (10) was
synthesized by nucleophilic substitution of 2,3-dichloro-1,4-
naphthoquinone (9) with equivalent of malononitrile in EtOH in
the presence of triethylamine.11 When equivalent amount of the
compound 10 and appropriate alkyl or arylamines were mixed
in EtOH and refluxed for 5 h, compounds 5a–e were formed.
The synthesized 1H-pyrrolo[3,2-g]quinoline-4,9-diones 4a–m
and 4,9-dioxo-4,9-dihydro-1H-benzo[f]indoles 5a–e were tested
in vitro for their growth inhibitory activity against pathogenic fungi
by the standard method.12 As indicated in Table 1, the MIC (mini-
mum inhibitory concentration) values were determined by com-
parison with fluconazole and 5-fluorocytosine as standard agents.
Among tested compounds 4a–m, many compounds generally
showed potent antifungal activity against the tested pathogenic
fungi. Actually, the activity of compounds 4g and 4l was superior
or comparable to those of 5-fluorocytosine against all tested fungi.
The compounds 4g and 4l completely inhibited the growth of all
Acknowledgments
This study was supported by a grant of the Korea Healthcare
Technology R&D Project, Ministry for Health, Welfare and Family
Affairs, Republic of Korea (A08-0414-AA1723-08N1-00010A).
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