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Irreversible enzyme inhibitors. XCIV. inhibition of dihydrofolic reductase with derivatives of 2,6‐diaminopurines
Author(s) -
Baker B. R.,
Santi Daniel V.
Publication year - 1967
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.5570040209
Subject(s) - chemistry , acylation , reductase , ring (chemistry) , enzyme , aryl , stereochemistry , biochemistry , organic chemistry , catalysis , alkyl
In order to gain additional information on the hydrophobic bonding region of dihydrofolic reductase, some derivatives of 2, 6‐diaminopurine with aryl or aralkyl groups at the N 6 , C 8 and N 9 ‐positions were investigated as inhibitors. Since none of the six compounds gave an increment in binding over the parent 2, 6‐diaminopurine, hydrophobic bonding to dihydrofolic reductase could not be detected with this ring system. Furthermore, 2, 6‐diaminopurine bridged from its 8‐position with methylene groups to the amino group of p ‐aminobenzoic acid also failed to show an increment in binding. The 8‐substituted 2, 6‐diaminopurines were synthesized by base‐catalyzed cyclodehydration of the appropriate 5‐acylamido‐2, 4, 6‐triaminopyrimidines; the latter compounds were readily prepared by selective acylation of tetraaminopyrimidine.