8-(OMEGA-AMINOALKYL)THEOPHYLLINES AND THEIR USE IN PREPARING FLUORESCENTLY LABELED DERIVATIVES FOR APPLICATIONS IN IMMUNOASSAY

Reaction of alkane-1,omega-diamines with 6-chloro-1,3-dimethylpyrimidi ne-2,4-dione under carefully controlled conditions gives minoalkylamin o)-1,3-dimethylpyrimidine-2,4-diones, which can be readily separated f rom traces of products of disubstitution after benzyloxycarbonyl prote ction. A sequence of nitrosation at the pyrimidine 5-position, thermal cyclization, and deprotection affords 8-(omega-aminoalkyl) derivative s of theophylline, an important drug in the treatment of asthma and re lated diseases. These 8-(omega-aminoalkyl)theophyllines can be coupled to fluorescein-5-isothiocyanate and to dansyl chloride, giving fluore scent derivatives of theophylline with applications in automated immun oassay of the drug in biofluids using the fluorescence capillary fill device.