Fundamentals of Medicinal Chemistry

synthesis, which is the conversion of N-carbamoyl aspartatic acid to dihydrooro-

tic acid. It was found that PALA bound 10

3

times more tightly to the enzyme than

the normal substrate, and was effective against some cancers in rats.

7.4 Drugs that target receptors

The binding of a drug to a receptor (Appendix 4) either inhibits the action of the

receptor or stimulates the receptor to give the physiological responses that are

characteristic of the action of the drug. Drugs that bind to a receptor and give a

similar response to that of the endogenous ligand are known as agonists,

whereas drugs that bind to a receptor but do not cause a response are termed

antagonists. Viruses, bacteria and toxins may also bind to the receptor sites of

specific tissues. This may cause unwanted pharmacological effects to occur.

7.4.1 Agonists

The response due to an agonist increases with increasing agonist concentration

until that response reaches a maximum (Figure 7.8(a) ). At this point, further

increases in agonist concentration have no further effect on the response.

Agonists often have structures that are similar to that of the endogenous

ligand (Figure 7.7). Consequently, the normal starting point for the design of

Receptor:

Endogenous ligand:

Agonists:

Histamine b−Adrenergic

NH 2

HN N

OH HO

HO

NHCH 3

NH 2 HN N

NH CH^3 2 HN N

CH 3 2-Methylhistamine 4-Methylhistamine Isoprenaline