Tioxamast

Exposure of non-sensitized Brown Norway (BN) rats to a 10%-ovalbumin aerosol induced an increase in the number of neutrophils in the broncho-alveolar lavage (BAL) fluid 3 and 6 h later but with no change in number of cells at 24 h. When the BN rats were actively sensitized (i.m. injection of 10 mg/kg ovalbumin and i.p. injection of killed Bordetella pertussis) and exposed 12-14 days later to a 10%-ovalbumin aerosol there was an increase in the number of eosinophils in the BAL fluid, maximal 24-48 h after the anaphylactic reaction. The increase in the number of neutrophils in the bronchial lumen 3 and 6 h after the anaphylactic reaction was larger than that obtained in non-specific inflammation and in contrast to this was still present 24-48 h after ovalbumin exposure. In passively sensitized BN rats exposed to ovalbumin aerosol, no inflammation appeared in the BAL fluid 24 h after the anaphylactic reaction. Various drugs, administered twice, 5 min and 5 h after the anaphylactic reaction, have been evaluated for their effects on the 24-h inflammation obtained in actively sensitized rats. Dexamethasone acetate (0.08 mg/kg i.p.) and theophylline (50 mg/kg i.p.) decreased the number of eosinophils and neutrophils. Ketotifen fumarate (12.5 mg/kg), cetirizine dihydrochloride (12.5 mg/kg), salbutamol (2 mg/kg), disodium cromoglycate (50 mg/kg) all given intraperitoneally, reduced the number of eosinophils. Tioxamast decreased the number of eosinophils at 12.5 mg/kg i.p. and by the oral route.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-4-arylthiazoles I [R = 2-pyridyl, 4-MeOC₆H₄, Ph, 4-FC₆H₄, 3,4-(OCH₂CH₂O)C₆H₃, etc., R¹ = H, Me, R² = H] react with R³O₂CCO₂R³ (R³ = Et, CMe₃, Me, Bu) in the presence of sodium alkoxides at room temperature to give I [R = 2-pyridyl, 4-MeOC₆H₄, Ph, 4-FC₆H₄, 3,4-(OCH₂CH₂O)C₆H₃, R¹ = H, R² = COCO₂Et; R = 4-MeOC₆H₄, R¹ = H, R² = COCO₂CMe₃, COCO₂Me, COCO₂Bu; etc.] in high yield.