Antifolate agents: a patent review (2006 - 2010).

Abstract

INTRODUCTION:

For > 50 years, drugs targeting the folate pathway have significantly impacted disease treatment as anticancer, antimicrobial and immunomodulatory agents. The discovery of novel antifolate agents with improved properties and superior activities remains an attractive strategy, both in academia and the pharmaceutical industry.

AREAS COVERED:

This review surveys the patent literature from 2006 to 2010 for small molecule inhibitors of enzymatic targets in the folate biosynthetic pathway.

EXPERT OPINION:

The pursuit of antifolates as anticancer and antimicrobial agents continues to be an active area of research. New patent disclosures reveal novel antifolate scaffolds, antifolates with improved drug-like properties and new strategies to effectively target cancer cells. The continued use of high resolution structural information has guided the discovery of several compounds. Owing to the need for high levels of potency and selectivity, especially in targeting pathogenic species, the use of high resolution crystal structures remains an important tool to guide the design of novel antifolates. Interestingly, the patents disclosing novel compounds were ones where X-ray crystallography was an integral component of the design process. Finally, a variety of new structures have been reported that may play an important role in the future development of therapeutic antifolates.

• Authors: Dennis L Wright, Amy C Anderson
• Journal: Expert opinion on therapeutic patents (Expert Opin Ther Pat) Vol. 21 Issue 9 Pg. 1293-308 (Sep 2011) ISSN: 1744-7674 [Electronic] England
• PMID: 21619471 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Folic Acid Antagonists
• Folic Acid
• Tetrahydrofolate Dehydrogenase

Topics

• Animals
• Folic Acid (biosynthesis)
• Folic Acid Antagonists (chemical synthesis, chemistry, pharmacology)
• Humans
• Models, Molecular
• Patents as Topic
• Structure-Activity Relationship
• Tetrahydrofolate Dehydrogenase (metabolism)