PREPARATION OF SUBSTITUTED N-PHENYL-4-ARYL-2-PYRIMIDINAMINES AS MEDIATOR RELEASE INHIBITORS

The role of immunologically released mediators, such as histamine, leu kotrienes, and platelet-activating factor, is well-established for ast hma and other allergic disorders. Developing therapeutic agents which would block mediator release from mast cells and other relevant cell t ypes would provide a rational approach to asthma therapy. Using human basophil as a screen, a series of 4-aryl-2-(phenylamino)pyrimidines wa s found which inhibited mediator release. These compounds were prepare d by condensing acetyl heterocycles with dimethylformamide dimethyl ac etal to form enaminones which are cyclized with aryl guanidines to giv e pyrimidines. After examining a large number of analogs, azol-1-yl)ph enyl]-4-(2-pyridinyl)-2-pyrimidinamine (1-27) was chosen for toxicolog ical evaluation.