Organic Chemistry of Drug Synthesis. Volume 7

recent atypical drug is a mixed agonist–antagonist at dopamine receptors.
The partial agonist activity should in theory avoid the effects of excessive
blockade. The compound at hand also acts on 5-HT receptors; this should
help patients who suffer from bipolar disorder in the depressed phase of
the disease. Alkylation of the nitrogen on the piperazine ( 167 ) with the
3-bromobenzyl mesylate ( 168 ), obtained by reaction of the corresponding
alcohol with methanesulfonyl chloride, affords the intermediate ( 169 ). The
additional benzene ring is added by Suzuki cross-coupling with phenyl-
boronic acid. Thus, the antipsychotic compound,bifeprunox( 170 ).^24

N

NH

O

HN

167

O

+

OSO 2 CH 3

Br

168

N

O

HN

O

N

Br

C 6 H 5 B(OH) 2

N

O

HN

O

N

(^169170)
Pd
The search for compounds that have a neuroprotective effect following
ischemic stroke is a recurrent theme in this chapter as well as in Chapter 3.
This search for effective drugs has ranged over a variety of biochemical
F
F
OH

• Cl
  O F
  F
  O O
  C 2 H 5 CON
  C 2 H 5 CON
  NH 2
  N
  S


• CH 3 SO 2
  N
  S
  HN N
  S
  NH
  HN
  (^172173174175)
  176 177 178
  F
  F
  O
  OH
  N
  N S
  HN
  179
  mechanisms, as well chemical structures. A benzothiazole moiety forms part
  of a compound that acts as a neuroprotectant in animal models. The (S)

2. FIVE-MEMBERED RINGS WITH TWO HETEROCYCLIC ATOMS 159