Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-[[[(2,4-Diaminopteridin-6-yl)methyl]amino]benzyl]-L-glutamic acid ("deoxoaminopterin", 1), a new aminopterin analogue containing a CH2 group in the side chain in place of the amide C = O, was synthesized by condensation of 2,4-diamino-6-(bromomethyl)pteridine with diethyl N-(p-aminobenzyl)-L-glutamate, followed by saponification with a stoichiometric amount of barium hydroxide in 50% ethanol. The apparent importance of the amide C = O group as a structural determinant of biological activity was indicated by the finding that 1 has 10- to 20-fold lower affinity for bacterial and mammalian dihydrofolate reductase than aminopterin, is not toxic to L1210 murine leukemia cells in culture at a concentration of up to 1.0 microM, and shows no antitumor effect in L1210 leukemic mice at doses as high as 240 mg/kg (q3d X 3).
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PMID:Methotrexate analogues. 16. Importance of the side-chain amide carbonyl group as a structural determinant of biological activity. 681 45