Synthesis and antifolate properties of 5, 10-methylenetetrahydro-8, 10-dideazaminopterin

…, WT Colwell, RL Kisliuk, Y Gaumont…

Index: DeGraw; Colwell; Kisliuk; Gaumont; Sirotnak Journal of Medicinal Chemistry, 1986 ,  vol. 29,  # 9  p. 1786 - 1789

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Citation Number: 10

Abstract

Is, X= Y= N: Z= NH b. X= Y a N; Z= NCH3 C, X= Y* N: ZzCH2. CHCH3 d, XaCH: YN: Z= CH2., X= N, Y= CH: Z= CH2 generally poor inhibitors of thymidylate synthase (TS) with values in the 100-300 pM range. However, it has been noted that conversion to the 5, 6, 7, 8tetrahydro derivatives can increase potency against TS by a factor of 10 or more in the aminopterin seriesa7 The mechanism of action of TS and structure-activity effects of ...