PROCESS FOR PRODUCING 4-PYRIMIDON COMPOUNDS OF NOVEL HISTAMINE H2-ANTAGONISTIC ACTIVITY

摘要

The invention provides new histamine H2- antagonist compounds of Structure 1 …… in which R<1> is hydrogen, lower alkyl, lower alkoxy, hydroxy, halogen, trifluoromethyl, nitro, amino, lower alkylamino, lower alkanoylamino, di(lower alkyl)amino or cyano; R<2> is in the 3-, 4- or 5- position and is hydrogen, or R<2> is lower alkyl substituted by amino, lower alkylamino, di(lower alkyl)amino, N-piperidino or N-pyrollidino, or R<2> is ethoxy or propoxy omega -substituted by amino, lower alkylamino, di(lower alkyl)amino, N-piperidino or N-pyrollidino; Y is methylene or oxygen and X is methylene or sulphur provided that one or two of the groups X and Y is methylene; Z is hydrogen or lower alkyl; A is C1-C5 alkylene or -(CH2)pW-(CH2)q- where W is oxygen or sulphur and p and q are such that their sum is from 1 to 4, and B is hydrogen, methyl, C3-C6 cycloalkyl, a heteroaryl group optionally substituted by one or more of the groups lower alkyl, lower alkoxy, halo, hydroxy and amino, or B is a naphthyl, 6-(2,3-dihydro-1,4-benzodioxinyl), a 4- or 5- (1,3-benzodioxolyl) group, or a phenyl group optionally substituted with one or more lower alkyl, lower alkoxy, halogen, aryl(lower alkoxy), hydroxy, lower alkoxy-lower alkoxy, trifluoromethyl, di(lower alkyl)amino, phenoxy, halophenoxy, lower alkoxyphenoxy, phenyl, halophenyl or lower alkoxyphenyl groups and pharmaceutical compositions containing them. A compound of Structure 1 can be prepared by reacting a compound of Structure 3 in which Q is nitroamino, loweralkylthio, benzylthio or halogen with an amine of Structure 2, in which …… R<3> is in the 3-, 4- or 5p position and is hydrogen, lower alkyl substituted by a group R<4>, or is R<4>CH2CH2O-or R<4>CH2CH2CH2O-, where R<4> is di(lower alkyl)amino, N-piperidino, N-pyrrollidino, a protected amino group or a protected lower alkylamino group, and where necessary any amino-protected group present in the substituent R<3> is removed.