make up polysaccharide can be viewed as acetals of aldehydes. These func-
tions on endogenous peptides and saccharides do occasionally interact
chemically to form cross-links. Accumulation of cross-linked proteins
with age is believed to lead to stiffening of tissues. Some of these processes
may go as far as to result in pathologic changes. A structurally very simple
thiazolium salt has shown activity in reversing such changes by breaking
cross-links. The compound is probably prepared by reaction of
dimethylthiazole ( 156 ) with phenacyl chloride ( 157 ). The productalageb-
rium chloride( 158 ) is said to show promise in treating effects traceable to
loss of tissue elasticity.
S
NH
+
O
Cl
156 157
S
O
Cl+ N+
158
The “glitazones” comprise a large series of antidiabetic compounds that
were introduced about a decade ago. The original hypoglycemic drugs
used for control of Type 2 diabetes were marked by the presence of a sul-
fonyurea pharmacophore. This function is replaced by a thiazolidinedione
group in the more recent glitazones. The synthesis of a very recent drug
candidate in this group begins with reduction of the carboxylic acid in
the naphthol ( 159 ) with diborane. The resulting carbinol is oxidized back
HO
CO 2 H
159
- BH 3
2. MnO 2 HO
CH=O
160
NH
S O
O
NH
S O
HO O
161
H 2
NH
S O
HO O
162
F
Cl
NH
S O
O
163
F
O
102 FIVE-MEMBERED HETEROCYCLES