Zomepirac

Chemical Name 5-(p-Chlorobenzoyl)-1,4-dimethylpyrrole-2-acetic acid 

Trade Name Manufacturer Country Year Introduced 

Ethyl 5-(p hlorobenzoyl)-1,4-dimethyl-3-ethoxypyrrole-2-acetate Sodium hydroxide Hydrogen chloride 

5-(p-Chlorobenzoyl)-3-carboxy-1,4-dimethylpyrrole-2-acetic acid A suspension of 17,3 g (0.0435 mol) of ethyl 5-(p hlorobenzoyl)-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 S-(p-chlorobenzoyl)-3-carboxy-1,4-dimethylpyrrole-2-acetate A suspension of 2.0 g of 5-(p-chiorobenzoyl)-3 arboxy-1,4-dimethylpyr role-2-acetic acid in 20 ml of 0.5% ethanol ic 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 arboxy-1,4-dimethylpyrrole-2-acetate, is filtered and dried, melting point 197°C to 198°C. 

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A nonsteroidal antiinflammatory agent in which the benzent ring carrying the acetic acid moiety has been replaced by a pyrrole grouping is zomepirac (10). It is synthesized from... 

C1JH14CINO5 33369-28-7) see Zomepirac 2 -carboxy-4-chloro-3-nitrobenzophenone (C14H8CINO5 85-54-1) see Chlortalidone [6/ -[6a,7p(Z)]]-l-[[2-carboxy-7-[[[[2-(l,l-dimethyl-ethoxy)- ,l-dimethyl-2-oxoethoxy]imino)[2-[(triphcnyl-methyl)amino]-4-thiazolyl]acetylJamino]-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]pyridinium inner salt... 

C7H4CI2O 122-01-0) see Acemetacin Benoxaprofen Bezafibrate Feclobuzone Fenofibrate Indometacin Moclobemide Progabide Rebamipide Zomepirac (2-chlorobenzoyi)cyciopentane (C12H13CIO 6740-85-8) see Ketamine... 

Involvement of tissue esterases is documented for zomepirac glucuronide, which undergoes rapid hydrolysis in vivo in the guinea pig and rabbit [30], Co-administration of (phenylmethyl)sulfonyl fluoride (an inhibitor of esterases) dramatically decreased the apparent plasma clearance of zomepirac glucuronide, and, in other experiments, strongly increased the apparent plasma clearance of zomepirac administered as such. 

A similar strategy was used for the modification of zomepirac, basically a COX-1 selective drug. The desired COX-2 selectivity was achieved by replacing the acetic acid group by other moieties such as a pyridazinone ring or an N-acyl aminosulfonyl phenyl group to yield RS-57067 and RS-1048934, respectively (Barnett et al., 2000)... 

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