J. D. Meester, W. Kraus, H. Plas
Jul 1, 1987
Citations
0
Influential Citations
8
Citations
Journal
Journal of Heterocyclic Chemistry
Abstract
Synthetic routes for the preparation of 3-alkyl-6-phenyl-4(3H)-pteridinones 6 and their corresponding 8-oxides 5 (R = CH3, C2H5, (CH2)2CH3, (CH2)3CH3, CH(CH3)C2H5, CH(CH3)2 and CH(C2H5)CH2OCH(OC2H5)2 are described and their reactivities towards xanthine oxidase from Arthrobacter M-4 are determined. Only the 3-methyl derivative of 6-phenyl-4(3H)-pteridinone and its 8-oxide i. e. 6a and 5a are found to be substrates although their reactivities are still very low. Oxidation takes place at C-2 of the pteridinone nucleus. All the 3-alkyl derivatives are less tightly bound to the enzyme than 6-phenyl-4(3H)-pteridinone. Introduction of the N-oxide at N-8 considerably lowers the binding of the substrates. Inhibition studies have revealed that 3-methyl-6-phenyl-4(3H)-pteridinone (6a) is a non-competitive inhibitor with a Ki-value of 47 μM and the 3-ethyl derivative (6b) an uncompetitive one with a Ki-value of 19.6 μM.