US 2003/0195240 A1 · Pharmaceutical compositions comprising proton pump inhibitors and gastrin/cholecystokinin receptor ligands

Abstract

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 —CH2COOR6, wherein R6 represents H, Me, Et, Pr or Bn), ═CH—, S— or —O—; n is from 1 to 4; R1 is H or C1 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; R2 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 R2 and R3 on the same carbon atom are linked to form a C3 to C6 carbocylic ring, or two R3 groups are absent from neighbouring carbon atoms which are linked by a double bond; or R2 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 R7 and R8 are independently selected from the groups recited above for R6), —CO—NR7—CH2—CO—NR8—, —CO—O—, —CH2—CH2—, —CH═CH—, —CH2—NR— or a bond; Q is —R9V, or (II) (wherein R9 is —CH2—; —CH2—CH2—; or (III) R9 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—SO2-Ph, SO2—NH—CO-Ph, —CH2OH, or a group of the formula —R10U, (wherein U is —COOH, tetrazolyl, —CONHOH— or —SO3H; and R10 is a bond; C1 to C6 hydrocarbylene, optionally substituted by hydroxy, amino or acetamido; —O—(C1 to C3 alkylene)-; —SO2NR11—CHR12—; —CO—NR11—CHR12—, R11 and R12 being independently selected from H and methyl; or —NH—(CO), —CH2—, c being 0 or 1); T is C1 to C6 hydrocarbyl, —NR6R7 (wherein R6 and R7 are as defined above), —OMe, —OH, —CH2OH, 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). 1

Claims35

Dependent claims

A pharmaceutical composition comprising a proton pump inhibitor and a compound of the formula (I)

24
wherein X and Y are independently ═N—, —N(R5)— (R5 being selected from H, Me, Et, Pr, Bn, —OH and —CH2COOR6, wherein R6 represents H, Me, Et, Pr or Bn), ═CH—, —S— or —O—
n is from 1 to 4;
R1 is H or C1 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;
R2 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 are linked to form a C3 to C6 carbocylic ring, or two R3 groups are absent from neighbouring carbon atoms which are linked by a double bond;
or R2 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—(NR)b (wherein a is 0 or 1, b is 0 or 1, and R7 and R8 are independently selected from the groups recited above for R6), —CO—NR7—CH2—CO—NR5—, —CO—O—, —CH2—CH2—, —CH═CH2, —CH═CH—, —CH═NR8— or a bond;
Q is —R9V, or
25
(wherein R9 is —CH2—;
—CH2CH2—;
or
26
or R9 and R8, together with the nitrogen atom to which R8 is attached, form a piperidine or pyrrolidine ring which is substituted by V;
V is —CO—NH—SO2-Ph, —SO2—NH—CO-Ph, —CH2OH, or a group of the formula —R10U, (wherein U is —COOH, tetrazolyl, —CONHOH— or —SO3H;
and R10 is a bond;
C1 to C6 hydrocarbylene, optionally substituted by hydroxy, amino or acetamido;
—O—(C1 to C3 alkylene)-;
—SO2NR11—CHR12—;
—CO—NR11—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, —NR6R7 (wherein R6 and R7 are as defined above), —OMe, —OH, —CH2OH, 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);
or a pharmaceutically acceptable salt thereof,
together with a pharmaceutically acceptable diluent or carrier.

28 more elements

Dependencies are inferred from the claim text.

Pharmaceutical compositions comprising proton pump inhibitors and gastrin/cholecystokinin receptor ligands

Life of this patent

Pharmaceutical compositions comprising proton pump inhibitors and gastrin/cholecystokinin receptor ligands

Life of this patent

Abstract

Claims35