Structural studies on bio-active compounds. Part 21. Acid-promoted debenzylations in antitumour 2,4-diamino-5-[4-(N-alkylbenzylamino)-3-nitrophenyl]-6-ethylp yrimidines.
Methylbenzoprim and ethylbenzoprim undergo debenzylation in hydrochloric acid. Two reaction mechanisms are proposed to explain this reaction, both of which involve a neighbouring group participation by the nitro group ortho to the tertiary amine fragment. The physical stability of dihydrofolate reductase inhibitors in the benzoprim class may influence the choice of a clinical candidate.
Griffin
R J
RJ
Department of Pharmaceutical Sciences, Aston University, Birmingham, UK.
Stevens
M F
MF
D000814:Aniline Compounds / Q000737:chemistry*; D004355:Drug Stability; D006358:Hot Temperature; D006851:Hydrochloric Acid / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry*
D000814:Aniline Compounds; D011743:Pyrimidines; C064625:methylbenzoprim; C079663:ethylbenzoprim; D006851:Hydrochloric Acid