N-Substituted pyridinones having histamine H.sub.2 -antagonist activity

A compound of the formula (I):

• ##STR15## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is 2- or 4- imidazolyl optionally substituted by one C.sub.1-6 alkyl, halo, trifluoromethyl or hydroxymethyl;
• 1-thiazolyl;
• 2-guanidino-4-thiazolyl optionally substituted by one chloro, bromo or C.sub.1-6 alkyl;
• 2-(5-amino-1,3,4-thiadiazolyl);
• 3-isothiazolyl optionally substituted by one chloro or bromo;
• 3-(1,2,5)-thiadiazolyl optionally substituted by one chloro or bromo;
• 2-pyridyl optionally substituted by one C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halo, amino or hydroxy moiety or substituted in the 4-position by a group R.sup.3 R.sup.4 N(CH.sub.2).sub.m --wherein R.sup.3 and R.sup.4 are independently hydrogen, C.sub.1-6 alkyl, aryl(C.sub.1-6)alkyl, thienyl(C.sub.1-6)alkyl, furyl(C.sub.1-6)alkyl, hydroxy(C.sub.1-6)alkyl, halo(C.sub.1-6)alkyl or C.sub.3-8 cycloalkyl;
• or together with the nitrogen atom to which they are attached form a 5-8 membered saturated ring;
• and m is 1 to 6;
• 2-furyl or 2-thienyl either optionally substituted in the 5-position by R.sup.5 R.sup.6 N(CH.sub.2).sub.m --wherein R.sup.5 and R.sup.6 are independently hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, halo(C.sub.1-6)alkyl, C.sub.3-6 alkenyl, aryl (C.sub.1-6)alkyl, C.sub.3-6 alkynyl, hydroxy(C.sub.1-6)alkyl, C.sub.1-3 alkoxy(C.sub.1-6)alkyl, trifluoro(C.sub.1-6)alkyl, amino(C.sub.1-6)alkyl, C.sub.1-3 alkylamino(C.sub.1-6)alkyl or di-(C.sub.1-3)alkylamino(C.sub.1-6)alkyl;
• or R.sup.5 and R.sup.6 together with the nitrogen atom to which they are attached form a 5-8 membered saturated ring;
• phenyl optionally substituted by one C.sub.1-6 alkyl, C.sub.1-6 alkoxy, hydroxy, halo, trifluoromethyl, nitro, amino, C.sub.1-6 alkylamino, C.sub.1-6 alkanoylamino, di-(C.sub.1-6)alkylamino or cyano and further optionally substituted in any of the 3-, 4-, or 5-positions on the phenyl ring by --(CH.sub.2).sub.m NR.sup.5 R.sup.6, --OCH.sub.2 CH.sub.2 NR.sup.5 R.sup.6 or --OCH.sub.2 CH.sub.2 CH.sub.2 NR.sup.5 R.sup.6 ;
• X is methylene, or if R.sup.1 is optionally substituted pyridyl or phenyl, X may also be oxygen;
• Y is sulfur or methylene, provided that at least one of X and Y is methylene;
• Z is hydrogen or C.sub.1-6 alkyl;
• A is C.sub.1-5 methylene or --(CH.sub.2).sub.p W(CH.sub.2).sub.q where W is oxygen or sulphur and p and q are such that their sum is from 1 to 4;
• R.sup.2 is a pyridone moiety substituted on the nitrogen atom by a group R.sup.7 wherein R.sup.7 is --(CH.sub.2).sub.r NR.sup.8 R.sup.9 wherein R.sup.8 and R.sup.9 are independently hydrogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-6 alkenyl, aryl(C.sub.1-6)alkyl, C.sub.3-6 alkynyl, hydroxy(C.sub.1-6)alkyl, C.sub.1-3 alkoxy(C.sub.1-6)alkyl, trifluoro(C.sub.1-6)alkyl, amino(C.sub.1-6)alkyl, C.sub.1-3 alkylamino(C.sub.1-6)alkyl or di-(C.sub.1-3)alkylamino(C.sub.1-6)alkyl;
• or R.sup.8 and R.sup.9 together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino or hexahydroazepino ring, and r is 2 to 6;
• or R.sup.7 is C.sub.1-6 alkyl, C.sub.3-7 cycloalkylC.sub.1-6 alkyl, hydroxyC.sub.2-6 alkyl, C.sub.1-6 alkoxyC.sub.2-6 alkyl, aryl(C.sub.1-6)alkoxyC.sub.2-6 alkyl, aryloxyC.sub.2-6 alkyl or aryl(C.sub.1-6)alkyl;
• and the pyridone moiety is optionally substituted on a carbon atom by one C.sub.1-4 alkyl, C.sub.1-4 alkoxy, hydroxy, halo, amino or phenoxy.