PROCESS FOR THE PREPARATION OF NITROGEN BRIDGEHEAD CONDENSED PYRIMIDINE COMPOUNDS, THE SALT, HYDRATES AND ISOMERS THEREOF, CERTAIN REPRESENTATIVES OF THE COMPOUNDS PREPARED AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

摘要

A b s t r a c t The invention concerns a new process for the preparation of nitrogen bridgehead condensed pyrimidine compounds of the general formula I (wherein R represents hydrogen or lower alkyl; R1 represents hydrogen, lower alkyl, carboxy or a derivative thereof or styryl; R2 represents hydrogen, optionally substituted lower alkyl; R3 represents hydrogen, optionally substituted substituted lower alkyl, aryl, aralkyl, halogen, carboxy or a derivative thereof, the group -(CH2)m-COOH (in which m is the integer 1, 2 or 3) or a carboxy derivative thereof, formyl, lower alkanoyl or a condensed derivative thereof; R4 represents hydrogen, optionally substituted alkyl, aryl optionally substituted by one or more substituents, optionally substituted aralkyl, a heterocyclic group optionally substituted by one or more substituents, the group -(CH2)m-Het (m is the integer 1, 2 or 3) Het is an optionally substituted heterocyclic group); R5 represents hydrogen C1-6 alkyl, aryl optionally substituted by one or more substituents, formyl, lower alkanoyl, optionally substituted aroyl or heteroaroyl; or R4 and R5 together with the nitrogen therebetween represent an optionally substituted monoor bicyclic heterocyclic ring, optionally containing further heteroatom) and pharmaceutically acceptable salts, hydrates, stereoisomers, optically active and geometric isomers and tautomers thereof, which comprises reacting a racemic or optically active compound of the general formula II (wherein R, R1, R2 and R3 are as defined above and X represents halogen) with a compound of the general formula III wherein R4 and R5 are as hereinbefore defined) or an acid addition salt thereof. Compounds of the general formula I wherein a) R3 represents aralkyl or halogen and R, R1 , R2 , R4 and R5 have the same meaning as defined above or b) R4 represents the group -(CH2)m-Het (m is the integer 1, 2 or 3 and Het represents an optionally substituted heterocyclic group) and R, R1, R2 , R3 and R5 have the same meaning as defined above) and pharmaceutically acceptable salts, hydrates, stereoisomers, optically active and geometric isomers and tautomers thereof are also included. The compounds of formula I possess interesting physiological properties, particularly antiallergic and/or antiasthmatic activity.