The search for new DHFR inhibitors: a review of patents, January 2001 – February 2005

Abstract

During the past 5 years, intense research activity has come from both private companies and academic institutions, aimed at the discovery of new, effective dihydrofolate reductase (DHFR) inhibitors. This important enzyme was discovered in the late 1950s, and, after nearly five decades, it still continues to draw the attention of researchers worldwide. Its low molecular weight makes it ideal as one of the main tools in molecular biology research: that is, in X-ray crystallography, NMR spectroscopy, kinetic measurements, and site-directed mutagenesis. This review will focus on the most recent developments published in the field, paying particular attention to promising DHFR inhibitors, their chemistry and biological evaluation, and to new chemical and pharmaceutical processes.

Keywords::

• biguanide derivative
• diaminopyrimidine derivative
• dihydrofolate reductase (DHFR)
• nonpolyglutamatable antifolate
• pyrimidopyrimidine derivative
• triazine derivative