Fluorine-containing Amino Acids and Their Derivatives. 5. Synthesis of Novel Fluorinated Analogues of the Antitumor Agent, Methotrexate

A b s t r a c t -Novel methotrexate analogues w i t h y -f l u a r o -o r cr-difluoromethylsubstitued-glutamic a c i d were synthesized f o r antitumor screening. Methotrexate (MTX), a p o t e n t i n h i b i t o r o f d ih y d r o f o l a t e reductase, i s an a n t i t u m o r agent i n wide c l i n i c a l use against various types o f cancers.' Progress i n pharmacological and physicochemical research on t h i s drug and d i h y d r o f a l a t e reductase i t s e l f has l e d t o an understanding o f t h e fundamentals of t h e mode o f a c t i o n and t h e mechanism o f t r a n s p o r t and metabolism, enabling more accurate drug design based on t h