PHARMACEUTICAL COMPOSITIONS COMPRISING PROTON PUMP INHIBITORS AND GASTRIN/CHOLECYSTOKININ RECEPTOR LIGANDS

摘要

Pharmaceutical compositions comprising a proton pump inhibitor and a compound of the formula (I) or its pharmaceutically acceptable salts, are useful in treating gastrointestinal disorders. X and Y are independently =N-,-N(R5)- (R5 being selected from H, Me, Et, Pr, Bn, -OH and -CH¿2COOR?6, wherein R6 represents H, Me, Et, Pr or Bn), =CH-, -S- or -O-; n is from 1 to 4; R1 is H or C¿1? to C15 hydrocarbyl wherein up to three C atoms may optionally be replaced by N, O and/or S atoms and up to three H atoms may optionally be replaced by halogen atoms; R?2¿ is selected from H, Me, Et, Pr and OH, each R2 being independently selected from H, Me, Et, Pr and OH when n is greater than 1; R3 (when n is 1) is selected from H, Me, Et and Pr; or (when n is greater than 1) each R3 is independently selected from H, Me, Et, and Pr, or two R3 groups on neighbouring carbon atoms which are linked by a double bond; or R?2 and R3¿ on the same carbon atom are linked to form a C¿3? to C6 carbocylic ring, or two R3 groups are absent from neighbouring carbon atoms which are linked by a double bond; or R?2 and R3¿ on the same carbon atom together represent an =O group; R4 is C1 to C15 hydrocarbyl wherein up to two C atoms may optionally be replaced by N, O and/or S atoms and up to two H atoms may optionally be replaced by halogen atoms; Z is -(NR7)a-CO-(NR8)b- (wherein a is 0 or 1, b is 0 or 1, and R?7 and R8¿ are independently selected from the groups recited above for R6), -CO-NR7-CH2-CO-NR8-, -CO-O-, -CH¿2?-CH2-, -CH=CH-, -CH2-NR?8¿- or a bond; Q is -R9V, or (II) (wherein R9 is -CH¿2?-; -CH2-CH2-; or (III) R?9 and R8¿, together with the nitrogen atom to which R8 is attached, form a piperidine or pyrrolidine ring which is substitued by V; V is -CO-NH-SO¿2?-Ph, SO2-NH-CO-Ph, -CH2OH, or a group of the formula -R?10¿U, (wherein U is -COOH, tetrazolyl, -CONHOH- or -SO¿3?H; and R?10¿ is a bond; C¿1? to C6 hydrocarbylene, optionally substituted by hydroxy, amino or acetamido; -O-(C1 to C3 alkylene)-; -SO2NR?11-CHR12¿-;-CO-NR?11 -CHR12-, R11 and R12¿ being independently selected from H and methyl; or -NH-(CO)¿c?-CH2-, c being 0 or 1); T is C1 to C6 hydrocarbyl, -NR?6R7¿ (wherein R?6 and R7¿ are as defined above), -OMe, -OH, -CH¿2?OH, halogen or trihalomethyl; m is 1 or 2; p is from 0 to 3; and q is from 0 to 2, with the proviso that q is 1 or 2 when Z is a bond).