Medicinal Chemistry

IMMUNOMODULATORS AND THEIR RECEPTORS 387

the body’s attack on the invading disease (e.g., a bacterial pathogen) while retaining the
ability to recognize “self” (thereby preventing the body from attacking itself). Agents
that augment the immune system are therefore important in the treatment of infectious
diseases, such as AIDS, or in the management of disorders in which the distinction
between “self” and “nonself” becomes blurred (e.g., cancer). Drugs that suppress
the immune system may also be of benefit in the treatment of disorders arising from
dysregulation of the immune system (e.g.,autoimmune diseases; see section 6.4) or in
helping a person retain an organ or tissue that has been transplanted from a donor. A wide
variety of other diseases, including disorders as diverse as rheumatoid arthritis or multi-
ple sclerosis, also benefit from the manipulation of the immune system. Finally, there is
an increasing recognition of the potential role of the immune system in an even greater
range of diseases not traditionally thought to arise from a dysfunctional immune system.
For instance, recent epidemiological studies suggest that anti-inflammatory agents may
play a role in delaying the onset or progression of Alzheimer’s disease.
Although the potential for the development of drugs that target the immune system
is obvious, the approach to be pursued in achieving this goal is not. The precise mole-
cular-level functioning of the immune system has yet to be fully elucidated and many
of the molecular details remain obscure. Accordingly, the medicinal chemistry of the
immune system is in its infancy when compared to the successes of drug design for
other messenger target systems such as neurotransmitters. Furthermore, since the
immune system tends to function at a cellular level, therapeutics designed to address
immune system targets may possibly be achieved more readily using biological
approaches in preference to classical drug molecule approaches. Stem cell research and
other biological therapeutics may offer a better long-term approach to disorders of the
immune messenger system. Nonetheless, small organic molecules have historically rep-
resented the most viable and successful approach to therapeutics; thus it is imperative
that drug design for immune targets be pursued.

6.1.1 Structures of the Immune System Relevant to Drug Action

In designing drugs to target immune-mediated messengers, it is important to appreciate
the anatomy and biochemistry of the immune system. The anatomy of the immune sys-
tem is not nearly as well delineated as that for the other messenger systems, such as the
nervous system. The “foot soldiers” of the immune system are the leukocytes(white
blood cells), which do the majority of the work within the immune system. Leukocytes
may be subcategorized as follows:

Agranular leukocytes (Agranulocytes)
Lymphocytes
T cells (TH1 cells, TH2 cells, CDL cells)
B cells
Monocytes
Granular leukocytes (Granulocytes)
Neutrophils
Basophils
Eosinophils