Organic Chemistry of Drug Synthesis. Volume 7

agents is not restricted to eukaryotic cells; the compounds also inactivate
microbes. A recent nitrogen mustard-containing compound is proposed
for useex vivoto inactivate pathogens in blood transfusion supplies. The
acridine portion ofamustaline( 6 ) is intended to intercalate in DNA, a
well-known property of this structural element, and thus bring the
mustard to the intended site of action. Excess drug that is not complexed
can be expected to be destroyed by blood enzymes or even by simple
hydrolysis. This will minimize exposure to unreacted mustard by a
patient who received treated blood. Construction of this agent starts by dis-
placement of chlorine from 9-chloroacrdine ( 1 ) by the terminal amine on a
so-called b-alanine ester ( 2 ) in the presence of sodium methoxide.
Saponification then yields the corresponding acid ( 3 ). Esterification of
the carboxyl group with triethanolamine ( 4 ) leads to the ester ( 5 ). The
free hydroxyl groups on this intermediate are then replaced by chlorine
by reaction with thionyl chloride. Thus, 6 is obtained.^1

N

Cl

1

N

H 2 N OC 2 H 5

O

2

+

1. NaOCH 3


2. NaOH
   N

HN OH

O

OH

OH

HO N OH

OH

N

HN O

O

N Cl

Cl

N

HN O

O

SO 2 Cl

3

4

6 5

Increased awareness and the rising incidence of Type 2 diabetes among
the aging population has led to the search for alternate drugs to the tra-
ditional hypoglycemic agents for treating the disease. Agents, such as vida-
gliptin (Chapter 5) and sitagliptan (Chapter 9) represent antidiabetic agents
for that act by mechanisms that differ significantly from the traditional
drugs. A naphthothiophene moiety provides the nucleus for a drug that
acts as an insulin sensitizer. This compound in addition acts as a peroxisome
proliferator activated receptor agonist (PPAR). In broad terms this agent

218 POLYCYCLIC FUSED HETEROCYCLES