Biomedical Engineering Reference
In-Depth Information
FIGURE 8.6
Macrocyclic agonists of the ghrelin receptor.
The above macrocycles possess an interesting compromise between peptidic and
nonpeptidic molecules, which retain the molecular recognition and selectivity of pep-
tides while exhibiting desirable PK-ADME profiles. In all cases, the corresponding
linear analogs were devoid of target activity.
In summary, several strategies are available to generate diverse collections of pep-
tidomimetic and semipeptidic macrocycles, which have demonstrated their potential
against a wide range of biological targets. Of particular relevance to drug discovery,
some of these subclasses have been associated with acceptable oral bioavailability
and a good PK-ADME profile, providing multiple clinical development candidates.
Reduction in the peptidic character of the final molecules has proven to be a judi-
cious choice, although the synthetic challenge is higher than that of all-peptidic
macrocycles.
