Tropical
Journal of Pharmaceutical Research, Aug 2011;
10(4): 463-473
http://dx.doi.org/10.4314/tjpr.v10i4.12
Abstract
Purpose:
Long-term clinical usage of nonsteroidal
anti-inflammatory drugs (NSAIDs) is associated with
significant side effects - gastrointestinal lesions,
bleeding and nephrotoxicity. Therefore, the discovery of
new safer antiinflammatory drugs represents a
challenging goal for this research area.
Methods:
Various derivatives of 3-(2-aminopyrimidin-4-yl) indoles
viz.
4-(4-substitutedphenyl)-6-(2-(4-substitutedphenyl)-1H-indol-3-yl)
pyrimidin-2-amine (4a-4r) were synthesized by
cyclization of
(3-(4-substitutedphenyl)-1-(2-(4-substitutedphenyl)-1H-indol-3-yl)
prop-2-en-1-one) of indole with guanidine hydrochloride
in the presence of sodium isopropoxide. Their structures
were confirmed by FTIR, 1H NMR and elemental
analysis. These compounds were investigated for their
analgesic, inflammatory and ulcerogenic activities.
Results:
All the compounds tested (4a-4r) showed analgesic and
inflammatory activities. Seven compounds (4d, e, h, j,
k, q, p) out of 18 compounds showed antiinflammatory
activity comparable to that of the reference standard,
indomethacin, but with much lower ulcerogenic action.
Compounds 4j and 4k showed 87.4 and 88.2 % inhibition of
paw edema, 78.5 and 76.6 % protection against acetic
acid-induced writhings and 0.89 and 1.12 of severity
index, respectively, compared to 92.7 %, 82.8 % and 2.2,
respectively, for indomethacin.
Conclusion:
The results show that incorporation of an appropriately
substituted pyrimidine ring in indole nucleus can afford
molecules with good analgesic and anti-inflammatory
activities but with reduced gastric irritation.
Keywords:
Synthesis, Indole, Pyrimidine, Anti-inflammatory
activity, Analgesic activity, Ulcerogenic effect.
