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Analogs of tetrahydrofolic acid. XIX. On the mode of binding of the pyrimidyl moiety of n‐(2‐amino‐4‐hydroxy‐6‐methyl‐5‐pyrimidylpropionyl)‐ P ‐aminobenzoyl‐l‐glutamic acid to 5,10‐methylenetetrahydrofolate dehydrogenase
Author(s) -
Baker B. R.,
Almaula Prabodh I.
Publication year - 1964
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570010513
Subject(s) - chemistry , moiety , thiol , stereochemistry , methyl group , amino acid , medicinal chemistry , group (periodic table) , organic chemistry , biochemistry
The synthesis of several analogs of the title compound (Ia) which had (a) replacement of the 4‐hydroxy group by thiol, (XXVIIIa), (b) replacement of the 6‐methyl group by 6‐phenyl (Ib), (c) replacement of the 2‐amino group by 2‐thiol (XXVI), or (d) replacement of both the 4‐hydroxyl and 6‐methyl groups by 4‐thiol and 6‐phenyl, respectively, have been described. The key intermediate was the appropriate 2,4,6‐trisubstituted5‐pyrimidyl‐propionic acids which were synthesized by suitable transformation of the 5‐pyrimidyl‐propionitriles (VIII and XII). Replacement (a) or (b) gave an improvement in inhibition of 5, 10 ‐ methylenetetrahydrofolate dehydrogenase, but the two changes in the same molecule (d) did not further increase inhibition. The 2‐amino group of the title compound (Ia) can be replaced by 2‐thiol without decreasing the inhibitory properties of Ia.