Synthesis of Ketoprofen Glucopyranoside Conjugates & Study of their Biological Properties

Jagdish K. Sahu, Amit Jain, Lopamudra Banerjee, R. N. Gupta

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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