ethanolamine moiety present in the great majority of compounds that act on
adrenergic receptors. Thus,solabegron( 56 ) is obtained.^10
CO 2 CH 3BrNO 2(HO 3 )B PdP(C 6 H 5 ) 3CO 2 CH 3NR 2Br NHCO 2 C(CH 3 ) 3
52CO 2 H
HN
NHH+CO 2 CH 3
HN
NHCO 2 C(CH 3 ) 3CO 2 CH 3
HN
OH NH^2O Cl+48 49
5051 ; R = O; R = H^535455
56Cl3. COMPOUNDS RELATED TO ANILINE
The structures of many monocyclic aromatic compounds have little in
common; the same is often the case for their biological activities. They
are consequently grouped here on the basis of some shared structural
element rather than biological activity. The three compounds that follow
have in common a nitrogen atom attached to the benzene ring.
A wide variety of compounds were tested as lipid-lowering agents some
five decades ago when association between heart disease and hyperlipdemia
was established. One of the more effective agents discovered in the course of
this research was the endogenous hormone thyroxin. Use of this compound
was severely limited by its effect on metabolic function and cardiac activity.
More detailed recent research has the thyroid receptor, like those for many
other hormones, exists as a pair of subtypes that are unevenly distributed.^11
One of these, theb-receptor, is virtually absent in cardiac tissue. Research
has thus started to identify compounds aimed at this receptor. The synthesis
of a selective blocker for thebselective agentaxitirome( 66 ), starts with the
reaction of the dianisyl ioidonium salt ( 57 ) with the nitrophenol ( 58 ) in the
presence of a cupric salt to give the product from displacement of iodine by
the phenoxide to give the diaryl ether ( 59 ). Acylation of intermediate ( 59 )
withp-fluorobenzoyl chloride ( 60 ) in the presence of titanium tetrachloride
yields the benzophenone ( 61 ). Reaction intermediate ( 61 ) with boron tribro-
mide then serves to cleave the methyl ether ( 62 ). Catalytic hydrogenation
serves to reduce the nitro group to afford aniline ( 63 ). This intermediate is
50 MONOCYCLIC AROMATIC COMPOUNDS