Definition
ChEBI: Zomepirac is a member of pyrroles, a member of monochlorobenzenes, a monocarboxylic acid and an aromatic ketone. It has a role as a non-steroidal anti-inflammatory drug and a cardiovascular drug. It is functionally related to an acetic acid.
Manufacturing Process
5-(p-Chlorobenzoyl)-3-carboxy-1,4-dimethylpyrrole-2-acetic acid: A
suspension of 17.3 g (0.0435 mol) of ethyl 5-(p-chlorobenzoyl)-1,4-dimethyl-
3-ethoxypyrrole-2-acetate in 170 g of 25% hydroxide is heated under reflux
for 3 hours. The suspension is poured into ice and the resulting yellow
solution is added to ice-hydrochloric acid with stirring. The precipitated solid is
collected by filtration, air dried and recrystallized from acetone containing
10% water to give 5-(p-chlorobenzoyl)-3-carboxy-1,4-dimethylpyrrole-2-acetic
acid as a white solid; melting point 253°C to 254°C.
Ethyl 5-(p-chlorobenzoyl)-3-carboxy-1,4-dimethylpyrrole-2-acetate: A
suspension of 2.0 g of 5-(p-chlorobenzoyl)-3-carboxy-1,4-dimethylpyrrole-2-
acetic acid in 20 ml of 0.5% ethanolic hydrogen chloride is heated under
reflux. The solid gradually dissolves. After 40 minutes a white crystalline solid
precipitates. The solution is cooled and the solid product, ethyl 5-(p-
chlorobenzoyl)-3-carboxy-1,4-dimethylpyrrole-2-acetate, is filtered and dried,
melting point 197°C to 198°C.
Ethyl 5-(p-chlorobenzoyl)-1,4-dimethylpyrrole-2-acetate: A 9.0 g (0.0255
mol) sample of ethyl 5-(p-chlorobenzoyl)-3-carboxy-1,4-dimethylpyrrole-2-
acetate is heated under nitrogen at 210°C to 230°C for 2 hours. Gas is
evolved. The residue is molecularly distilled in a sublimator at 195°C, 0.05
mm/Hg. The sublimate is recrystallized from cyclohexane to give ethyl 5-(p-
chlorobenzoyl)-1,4-dimethylpyrrole-2-acetate as a white solid, melting point
107°C to 109°C.
5-(p-Chlorobenzoyl)-1,-4dimethylpyrrole-2-ecetic acid: A suspension of 4.0 g
(0.0125 mol) of ethyl 5-(p-chlorobenzoyl)-1,4-dimethylpyrrole-2-acetate in 26
ml of 0.5 N sodium hydroxide (0.013 mol) is heated under reflux for 30
minutes. The resulting solution is acidified with dilute hydrochloric acid, and
the precipitated solid is collected by filtration, air dried and recrystallized from
2-propanol to give 5-(p-chlorobenzoyl)-1,4-dimethylpyrrole-2-acetic acid as a white crystalline solid, melting point 178°C to 179°C.
World Health Organization (WHO)
Zomepirac, a nonsteroidal anti-inflammatory agent, was
introduced in 1979 for the treatment of rheumatic disorders and the management of
moderate to severe pain. By 1983 its use had been associated with serious allergic
reactions, including five deaths from anaphylaxis. This led to voluntary withdrawal
of the drug from markets worldwide by the major manufacturer.
