chapter  H3
3 Pages

Simplification Of Complex Molecules

WithGraham Patrick

Complex natural products tend to have several functional groups. Some of these functional groups will be important for activity, but others may cause side effects by allowing the molecule to bind to other targets. Removing such groups could therefore make the compound more selective in its action. Many complex molecules contain several rings. However, some of these rings may be surplus to requirements and could be removed without affecting the pharmacophore. The strategy of removing rings has been beneficial in a wide range of drugs, including the opiate analgesics. The removal of rings from morphine has resulted in analogs in which analgesic activity has been retained and which are much easier to synthesize. Removing asymmetric centers is straightforward if the asymmetric centers are in nonessential regions of the skeleton, since that part of the skeleton can be removed entirely. However, other asymmetric centers may be present in portions of the skeleton that are responsible for holding the pharmacophore in place.