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107
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17–30.
phenylbutazone and naproxen, are known to cause
acute or chronic hepatitis, confluent or spotty necrosis,
cholestatic hepatitis and/or fatty change. This shows
the importance of examining the liver tissues to better
assess the safety of NSAIDs. In some cases like 1c, 1d,
2a, 2b, and 4a (moderate, ++) macro and microvesicu-
lar fatty change and several scattered mild (+) focal
spotty necrosis were observed. Multiple foci of spotty
necrosis (moderate, + +) was seen with compounds 2a
and 3c. Cholestatic hepatitis was observed with the
compounds 1c, 2a, 3d, and 4a (Table 4).
In conclusion, a new series of compounds showing
anti-inflammatory properties was synthesized. Among
them in particular compounds 2-(2-naphthyloxy-
methyl)-5-methylamino-1,3,4-oxadiazole 2a and 5-(2-
naphthyloxymethyl)-4-methyl-1,2,4-triazole-3-thione 4a
were found to have a superior anti-inflammatory profile
with low gastric ulceration incidence with similar toxic
profiles of reference NSAIDs in the liver.
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Acknowledgements
This work is supported by Hacettepe University Re-
search Fund (Project: 98.01.301.002). Procedures in-
volving animals and their care were conducted in
conformity with international laws and policies and the
studies on animals accepted by Hacettepe University
Ethic Council (99/15).
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