Antifolate agents: a patent review (2010 - 2013).

INTRODUCTION: The folate biosynthetic pathway, responsible for the de novo synthesis of thymidine and other key cellular components, is essential in all life forms and is especially critical in rapidly proliferating cells. As such, druggable targets along this pathway offer opportunities to impact many disease states such as cancer, infectious disease and autoimmune disease. In this article, recent progress on the development of antifolate compounds is reviewed. AREAS COVERED: The evaluation of the patent literature during the period 2010 - 2013 focused on any compounds inhibiting recognized targets on the folate biosynthetic pathway. EXPERT OPINION: The folate pathway constitutes a well-validated and well-characterized set of targets; this pathway continues to elicit considerable enthusiasm for new drug discovery from both academic and industrial pharmaceutical research groups. Within the pathway, the enzymes dihydrofolate reductase and thymidylate synthase persist as the most attractive targets for new drug discovery for the treatment of cancer and infectious disease. Importantly, new potential targets for antifolates such as those on the purine biosynthetic pathway have been recently explored. The use of structure-based drug design is a major aspect in modern approaches to these drug targets.