Imidazo[1,5-d][1,2,4]triazines as potential antiasthma agents

Abstract

By using inhibition of histamine release from antigen-challenged, sensitized human basophils as a means of identifying a potentially prophylactic drug for the treatment of asthma, a series of substituted imidazo[1,5-d][1,2,4]triazines were found, which were active. These compounds were prepared by treating imidazolecarboxaldehydes with excess Grignard agent and then oxidizing the resulting alcohols to ketones with Jones reagent. Pyrolysis of a mixture of ketone and methyl carbazate at 200 degrees C in diphenyl ether produced the desired imidazo[1,5-d][1,2,4]triazines. Those compounds with the greatest basophil activity were tested for in vivo activity in the mouse passive cutaneous anaphylaxis (PCA) and the guinea pig passive anaphylaxis tests. The best compounds, 1-ethyl-8-methyl-6-propylimidazo[1,5-d][1,2,4]triazin-4(3H)- one (4-17) and 1,8-dimethyl-6-propylimidazo[1,5-d][1,2,4]triazin-4-(3H)-one (4-16) were chosen for further study.

New Chiral and Achiral Imines and Bisimines Derived from 2‐Phenyl‐1H‐imidazole‐4‐carbaldehyde. Synthesis, Structural Studies and Complexation Stability Constants

“…Alternative procedure with ammonium chloride in aqueous ammonia providing only 32% of yield was also used . The oxidation of 1 to 2‐phenyl‐1 H ‐imidazole‐2‐carbaldehyde ( 2 ) using the modified instructions was performed . The refluxing of reaction mixture for exactly 55 min via NO x elimination from concentrated nitric acid resulted in a higher yield of 55% (published is 41%).…”

“…Modified synthesis was performed according to Paul . To 166 g (2.63 mol, 120 mL) of concentrated nitric acid, 20 g (115 mmol) of 1 was added.…”

Design and synthesis of optically active 2‐phenylimidazolecarboxamides featuring amino acid motive

“…The first two series were generated from a 2-phenylimidazole-4-carboxylic acid (4) and its derivatization by amino acid esters (1a-f) and amides (2a-d), respectively. The starting carboxylic acid 4 was prepared via the HNO 3 oxidation of the 2-phenyl-4-hydroxymethylimidazole, generated from dihydroxyacetone [26]. Since this methodology of oxidation was mainly developed for the synthesis of 2-phenylimidazole-4-carbaldehyde, particular attention should be paid to the conditions of this reaction step.…”

Product Class 5: Azaindolizines with Two Nitrogen Atoms in the Five-Membered Ring

“…17 (Six-Membered Hetarenes with Two Unlike or More than Two Heteroatoms and Fully Unsaturated Larger-Ring Heterocycles). A little has been published on biological studies (for antitumor [172,173] and antiasthma activity [174] ) on derivatives of this subclass. [167] The available literature on these ring systems is rather sparse: some NMR studies, [168,169] X-ray investigations, [170] and theoretical calculations [171] have been reported.…”