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Abstract: Glucopyranoside Conjugates of
Ketoprofen have been synthesized and evaluated for
anti-inflammatory, analgesic and ulcerogenic activities.
The results designate significant augmentation in
analgesic and anti-inflammatory activity and diminution
in gastrointestinal toxicity.
1. Introduction
Traditional non steroidal anti-inflammatory drugs (NSAIDs)
are used in treatment of mild to moderate pain and as an
adjunct to opioids in the management of moderate to
severe pain. The clinical effects of NSAIDs are based on
the inhibition of the enzyme cyclooxygenase (COX), which
catalyses the rate limiting step in the formation of
prostanoids, prostaglandins (PGs) and thromboxane A2
(TxA2). PGs are ubiquitous compounds that mediate a
variety of physiologic and pathologic processes. Under
normal physiologic conditions, PGs play an essential
homeostatic role in cytoprotection of gastric mucosa,
hemostasis, renal function, gestation and parturition.
It is a well accepted fact that gastrointestinal lesions
produced by NSAIDs are due to two different mechanisms:
(a) direct contact with gastric mucosa through oral dose
and (b) systemic effect which may be manifested by after
intravenous dosing. Ketoprofen (1), a 2-arylpropinoic
acid, belongs to the family of nonsteroidal
anti-inflammatory drugs (NSAIDS). It has similar
pharmacological actions to other drugs in this class
such as ibuprofen, fenoprofen and naproxen. Ketoprofen
has been used extensively in treatment of chronic
rheumatoid arthritis and various painful conditions in
various species. The principal mechanism of action is
considered to be via inhibition of cyclo-oxygenase
mediated generation of prostanoids.8 Temporarily masking
the acidic group of NSAIDs with a view to decrease the
gastrointestinal toxicity due to direct injury has been
postulated. The purpose of this study was to mask the
free acidic group by synthesizing its glucopyranoside
derivative and evaluate it’s anti-inflammatory activity,
analgesic activity and gastrointestinal toxicity.
2. Experimental
2.1. Chemistry
Melting points were determined by Superfit Melting Point
Determination Apparatus in open capillary tube and were
uncorrected (Table 1). IR spectra were taken on Nujol
mulls between salt plates. 1H-NMR spectra were recorded,
in CDCl3 solution, on a Bruker Avance II 400
spectrometer. The chemical shift are reported in part
per million (δ, ppm) downfield from tetramethylsilane,
which was used as internal standard. Mass spectra were
also recorded in CDCl3 solution.
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