Pyrimidine synthesis inhibitors

Pyrimidine biosynthesis occurs both in the body and through organic synthesis.  Pyrimidine synthesis inhibitors are used to inhibit this process and are classified as both antimetabolites inhibiting the metabilic process and immunosuppressants.  They are principally used to treat so called 'auto-immune diseases' like  rheumatoid arthritis and psoriatic arthritis. 

An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism.   Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid. Main representatives of these drugs are:

• purine analogues  - purine synthesis inhibitors that inhibit the synthesis of purine
• pyrimidine analogues  - pyramidine synthesis inhibitors that inhibit the synthesis of pyramidine
• antifolates 

 Anti-metabolites thus masquerade as a purine (azathioprine, mercaptopurine) or a pyrimidine, or folic acid chemicals that become the building-blocks of DNA. They prevent these substances becoming incorporated in to DNA during the S phase (of the cell cycle), stopping normal development and division. 

As you can see, the presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are sometimes used as chemotherapy for cancer.

So how, you might ask, can this class of drugs help in suppressing the immune system.  Well many of those cells are used in the immune system response – they are leukocytes for example and T cells.  Thus these drugs inhibit the production of our immune system cells – there are not as many attacking cells produced.

Observations

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• Leflunomide and Arava