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Coupling to the pyrimido[4,5‐ b ][1,4]oxazine ring system: Synthesis of potential antifolates
Author(s) -
Winchester Merritt J.,
Zappone Lawrence J.,
Skinner Charles G.
Publication year - 1981
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.5570180303
Subject(s) - chemistry , dihydrofolate reductase , ring (chemistry) , stereochemistry , side chain , coupling (piping) , oxazines , amino acid , combinatorial chemistry , enzyme , organic chemistry , biochemistry , mechanical engineering , engineering , polymer
The ability of 2‐amino‐4‐hydroxy‐7 H ‐pyrimido[4,5‐ b ][1,4]oxazine derivatives to inhibit dihydrofolate reductase led to a search for means of synthesizing new side chain substituted analogs of this marginally stable pyrimidooxazine system. A study of the synthesis and use of 6‐functionalized pyrimido[4,5‐ b ][1,4]oxazines for coupling side chains was begun and has now revealed methods for coupling p ‐aminobenzoic acid with 2‐amino‐4‐hydroxy‐6‐carboxy‐7 H ‐pyrimido[4,5‐ b ][1,4]oxazine and hydrolyzed 2‐amino‐4‐hydroxy‐6‐carbe‐thoxymethylene‐6,7‐dihdyro‐5 H ‐pyrimido[4,5‐ b ][1,4]oxazine. The products are of interest for evaluation as potential antifolates.