Page 232 - Medicinal Chemistry Self Assessment

6. Evaluation of the to inhibit acetylcholinesterase.

meta orientation para orientation
CH 3 CH 3 CH 3
H 3 C N O CH 3 N CH 3
N O
O CH 3 H 3 C N O CH 3
2.24 Rivastigmine 221

Rivastigmine CH 3 para Analog of
Rivastigmine

tertiary amine and carbamate of rivastigmine can mimic the quaternary nitrogen atom and ester of
acetylcholine respectively. The aromatic ring provides structural rigidity; however, conformational
flexibility of its substituents allows these functional groups to be properly oriented when they are
Answer:
located meta to one another. As shown below, para orientation of these substituents does not allow
For rivastigmine to interact with acetylcholinesterase, it must contain structural features that mimic
for proper orientation. Although the requisite functional groups are present, they are located too far
apart from one another and, therefore, cannot interact effectively with acetylcholinesterase.

The meta orientation allows for similar distances

The para orientation places the functional groups
too far apart from one another