Biomedical subjects

J A Brockman

Publications and source records attributed to J A Brockman.

3 recordsLinked to original sources

PubMed1990

Preparation of triazolo[1,5-c]pyrimidines as potential antiasthma agents.

With the use of the human basophil histamine release assay, 5-aryl-2-amino[1,2,4]triazolo[1,5-c]pyrimidines were found to be active as mediator release inhibitors. These compounds were prepared by reacting arylamidines with sodium ethyl formylacetate or with ethyl propiolate to give pyrimidinones. Treatment with phosphorus oxychloride gave a chloropyrimidine, which was converted to a hydrazinopyrimidine with hydrazine. Cyclization, using cyanogen bromide, gave the triazolo[1,5-c]pyrimidines, after a Dimroth rearrangement. Following a structure-activity evaluation, the 5-[3-(trifluoromethyl)phenyl]-2-amino (8-10), 5-(3-bromophenyl)-2-amino (8-13), 5-[3-(difluoromethoxy)-phenyl]-2-amino (8-11), and 5-(4-pyridinyl)-2-amino (6-7) compounds were found to have the best activity. They were chosen for further pharmacological and toxicological study.

Animals↗

PubMed1985

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

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.

Anaphylaxis↗

PubMed1979

A capillary diffusion method for determining hemolytic complement activity in undiluted serum .

A method is presented for measuring the hemolytic activity of undiluted guinea pig serum. Undiluted serum is placed in contact with a column of sensitized sheep red blood cells in an agar matrix in a capillary tube. After incubation, the length of the zone of lysis is measured. Comparison with a standard curve prepared from dilutions of a pool of normal serum allows relative quantitation. Because the serum is not diluted, this method allows detection of reversible inhibitors of the complement system.

Animals↗