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Paul, Rolf; Brockman, John A; Hallett, W. A; Hanifin, John W; Tarrant, M. Ernestine; Torley, Lawrence W; Callahan, Francis M; Fabio, Paul F; Johnson, Bernard D
Journal of medicinal chemistry 28, Številka: 11Journal Article
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 imidazo1,5-d1,2,4triazines 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 imidazo1,5-d1,2,4triazines. 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-propylimidazo1,5-d1,2,4triazin-4(3H)- one (4-17) and 1,8-dimethyl-6-propylimidazo1,5-d1,2,4triazin-4-(3H)-one (4-16) were chosen for further study.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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