Fundamentals of Medicinal Chemistry

(Brent) #1
the receptor. Furthermore, in order to bind to the receptor, the conformations

and configuration of the new antagonist should be complementary to the

structure of the receptor. If sufficient data is available, molecular modelling

docking techniques (see section 5.5) can yield valuble insight into these aspects

of the binding of the potential antagonist to the receptor.

7.4.3 Partial agonists


Partial agonists are compounds that act as both agonists and antagonists. They

are believed to act as antagonists by preventing the endogenous ligand binding

to the receptor but at the same time weakly activating the receptor. This is

thought to cause a weak signal to be sent to the appropriate domain of the

receptor. The net result of these opposing effects is that a much higher dose of

the agonist is required to obtain the maximum response. Furthermore, this

response is less than that of pure agonists with similar structures. Most drugs

are partial agonists.

7.5 Drugs that target nucleic acids


Drugs that target DNA and RNA (see Chapter 1) either inhibit the synthesis of

DNA and RNA or act on existing nucleic acid molecules. Those that inhibit the

synthesis of nucleic acids usually act as antimetabolites and enzyme inhibitors.

Those that act on existing nucleic acid molecules may for convenience by

broadly classified as intercalating agents, alkylating agents and chain cleaving

agents. In both cases, the net result is the prevention or slowing down of cell

growth and division. Consequently, the discovery of new drugs that target

existing DNA and RNA is a major line of approach for the development of

new drugs for the treatment of cancer (see Appendix 10) and bacterial and other

infections due to microorganisms.

7.5.1 Antimetabolites


Antimetabolites are compounds that block the normal metabolic pathways

operating in cells. They act by either replacing an endogenous compound in

the pathway by a compound whose incorporation into the system either results

in a product that can no longer play any further part in the pathway or inhibits

DRUGS THAT TARGET NUCLEIC ACIDS 147

Free download pdf