ABSTRACT
Several known antiallergic agents, including cromolyn sodium and a series of pyrido[2,1-b]quinazolines, inhibit human alkaline phosphatase (ALP), a membranal enzyme associated with calcium uptake in certain tissues. A comparison of ALP and rat passive cutaneous anaphylaxis (PCA) inhibition indicates that PCA inhibition may be associated with drug-ALP interaction, since ALP inhibition potency parallels PCA inhibitory activity. The unpredictability of the PCA test toward clinical efficacy could in part be related to the uncompetitive nature of these inhibitors. The results also suggest that alkaline phosphatase may be a component of membranal calcium channels.
Subject(s)
Alkaline Phosphatase/antagonists & inhibitors , Cromolyn Sodium/pharmacology , Hypersensitivity/drug therapy , Quinazolines/chemical synthesis , Animals , Chemical Phenomena , Chemistry , Female , Humans , In Vitro Techniques , Leukocytes/enzymology , Passive Cutaneous Anaphylaxis/drug effects , Placenta/enzymology , Pregnancy , Quinazolines/pharmacology , RatsABSTRACT
A series of substituted 10-oxo-10H-pyridazino[6,1-b]quinazoline-2-carboxylic acids was prepared and evaluated as antiallergy agents. The 8-chloro and unsubstituted analogues were more potent that cromolyn sodium and doxantrazole intravenously in the rat PCA test. None of the analogues possessed significant oral activity.
Subject(s)
Hypersensitivity/drug therapy , Quinazolines/chemical synthesis , Animals , Passive Cutaneous Anaphylaxis/drug effects , Pyridazines/chemical synthesis , Pyridazines/pharmacology , Quinazolines/pharmacology , Rats , Structure-Activity RelationshipABSTRACT
A series of substituted 11-oxo-11H-pyrido[2,1-b]quinazoline-8-carboxylic acids were prepared and evaluated as antiallergy agents. Several analogues were orally active. 2-Methyl-11-oxo-11H-pyrido[2,1-b]quinoazoline-8-carboxylic acid (6) was superior to cromolyn sodium and doxantrazole orally and intravenously in the rat PCA test and a rat allergic bronchospasm model.
Subject(s)
Hypersensitivity/drug therapy , Quinazolines/chemical synthesis , Animals , Bronchial Spasm/drug therapy , Bronchial Spasm/immunology , Bronchial Spasm/physiopathology , Histamine Release/drug effects , In Vitro Techniques , Mast Cells/drug effects , Mast Cells/immunology , Passive Cutaneous Anaphylaxis/drug effects , Pulmonary Ventilation/drug effects , Quinazolines/pharmacology , Rats , Structure-Activity RelationshipABSTRACT
A new series of 11-oxo-11H-pyrido[2,1-b]quinazolinecarboxylic acids and related analogues has been synthesized and evaluated as potential antiallergy agents. In the rat PCA test, 11-oxo-11H-pyrido[2,1--b]quinazoline-8-carboxylic acid is orally active and more potent than cromolyn sodium or doxantrazole intravenously.
