11

Isoxicam

W.W.DOWNIE
M. 1. GLUCKMAN
B. A. ZIEHMER
J.A. BOYLE

In a search for novel non-steroidal anti-inflammatory drugs (NSAIDs) of

the non-carboxylic acid type, a drug discovery programme was instituted
by Warner-Lambert in 1966. By February 1967 a number of enolic acid
compounds had been synthesized for biological screening, and the first
major lead compound was synthesized in June 1969, prior to the issue of
the Belgian piroxicam patent in August 1969. It is accordingly interesting
to note that both isoxicam and piroxicam were developed as the result of
totally independent research efforts.

CHEMISTRY

Isoxicam, 4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-2,3-benzo-
thiazine-B-carboxamide Ll-dioxide, is a benzothiazine derivative of the
oxicam group of drugs (Zinnes et al, 1982). It has a molecular weight of
335.3 and a pKa of 3.65. It is a thermally stable, non-hygroscopic, non-
volatile, odourless, white to light beige crystalline powder. The structural
formula is shown in Figure 1.

ro
OH 0
ll
/'" I "C-NH~
~ ....N, N<, _ ,)l....
80 2 CH 3 0 CH 3

Figure 1. Structure of isoxicam.

ANIMAL PHARMACOLOGY

Carrageenan rat paw oedema

The effects of five NSAIDs on carrageenan-induced rat paw oedema have
been examined (DiPasquale et aI, 1975). NSAIDs were administered
Clinicsin Rheumatic Diseases-Vol. 10, No.2, August 1984 385