Antiallergic activity of 2-phenyl-8-azapurin-6-ones

Abstract

The synthesis and antiallergic activity in the rat passive cutaneous anaphylactic reaction of a series of 2-phenyl-8-azapurin-6-ones are described. Early in the investigation, a linear free-energy equation was established in which the activity was related to the size and hydrogen bonding capacity of the ortho substituent in the phenyl ring. This relationship was used to provide guidance and limits for subsequent work leading to 2-o-propoxyphenyl-8-azapurin-6-one which is 40 times more potent than disodium cromoglycate. It is suggested that good antiallergic activity in this series is associated with coplanarity of the phenyl group with the azapurin-6-one which would be favored by a high degree of hydrogen bonding.

Studies on Azole-to-Azole Interconversion − An Interesting Case of Absence of a “Primary Steric Effect” in the Ring-Degenerate Equilibration betweenortho-Substituted 3-Aroylamino-5-methyl-1,2,4-oxadiazoles and 3-Acetylamino-5-aryl-1,2,4-oxadiazoles in Methanol

“…Comparison with 1 H NMR spectra (Table 3) of other pairs of ortho and para isomers for which intramolecular hydrogen-bonded structures were not possible (10b and 10n, and also 10e and 10q) strengthened this interpretation: the NϪH signals were always observed in the δ ϭ 7.8Ϫ8.7 range in CDCl 3 and in the δ ϭ 11.4Ϫ11.8 range in DMSO for both ortho and para isomers, respectively. The situation observed is not new, and is reminiscent of the findings of Wooldridge et al, [19] who reported on the occurrence of strong intramolecular hydrogen bonding between an ortho-alkoxy substituent and the N(1)ϪH proton of a series of 2-aryl-8-azopurin-6-ones. As a matter of fact, the proton of a pyrimidone ring amide group gives an intramolecular hydrogen bond with the oxygen atom of the alkoxy group.…”

Recent Developments in the Chemistry and in the Biological Applications of Amidoximes

“…Chemically, approaches towards amidines lay on the reduction of amidoximes (Scheme 5), either via catalytic hydrogenation with palladium in charcoal in the presence of acetic acid [25], or reduction with Zn in acetic acid [26] or transition metal catalysis in general [27][28][29]. Scheme 5.…”

Ethyl 4-(4-methoxyphenyl)-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylate

“…It has been suggested that the substituent effect may be attributable to intramolecular hydrogen bonding between the alkoxy oxygen and the proton of the pyrimidine ring NH group (Broughton et al, 1975). Recently, much attention has been devoted to dihydropyrimidine derivatives because of their significant therapeutic and medicinal properties (Kappe, 1993;Kappe et al, 1997).…”