Pharmaceuticals–Some Important Drugs - Fundamentals of Industrial Chemistry: Pharmaceuticals, Polymers, and Business - page 197

CO 2 H

O

H

O

N

Repaglinide
Thiazolidinediones are a class of insulin-sensitizing drugs. Their use is lim-
ited because they can cause congestive heart failure. Troglitazone (Rezulin ® )
was approved in the U.S. in 1997 followed in 1999 by pioglitazone and rosigli-
tazone [47]. Troglitazone was withdrawn from the market in 2000 due to liver
toxicity. Pioglitazone is available as the hydrochloride salt (Actos ® , Takeda)
and rosiglitazone as the maleate salt (Avandia ® , GlaxoSmithKline). There
are also concerns with pioglitazone and rosiglitazone (risk of cardiac events)
and this precludes their use in some patients.

Thiazolidinedione ring

O

NH

S

O

O

O

HO

Troglitanzone

O

CO 2 H

CH 3

NH

S

N

N

CO 2 H

O

O

Rosiglitazone maleate

O

N

NH

HCl

S

O

O

Pioglitazone hydrochloride

Notice that there is a chiral carbon in these structures. They are present as
a racemic mixture of enantiomers. The enantiomers interconvert rapidly in
vivo and there is no difference in the pharmacologic activity between the two
enantiomers.

Chiral carbon

O

NH

S

R

O

O

Incretin hormones such as glucagon-like peptide 1 (GLP-1) cause

-cells. Exenatide (Byetta ® , Amylin insulin release from the pancreatic β