Cholecystokinin antagonists useful for treating depression

Claim 1

A method for the treatment of idiopathic depression which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a cholecystokinin antagonist or a pharmaceutically acceptable salt thereof in unit dosage form of formula wherein n is 1 or 2 R 1 is a phenyl group mono-, di-, or tri-substituted with linear or branched C 1 -C 4 groups, which may be the same or different, or with halogens, with a cyano group or with a trifluoromethyl group; R 2 is selected from the group consisting of morpholino, piperidino, and amino with one or two linear, branched, or cyclic alkyl group substituents containing from 1 to 8 carbon atoms which may be the same or different.

Claim 2

A method for the treatment of idiopathic depression which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a cholecystokinin antagonist or a pharmaceutically acceptable salt thereof in unit dosage form of formula wherein n is 1 or 2 R 1 is a phenyl group mono-, di-, or tri-substituted with linear or branched C 1 -C 4 groups, which may be the same or different, or with halogens, with a cyano group or with a trifluoromethyl group; R 2 is selected from the group consisting of morpholino, piperidino, and amino with one or two linear, branched, or cyclic alkyl group substituents containing from 1 to 8 carbon atoms which may be the same or different.

Claim 5

A method for the treatment of idiopathic depression which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a cholecystokinin antagonist or a pharmaceutically acceptable salt thereof in unit dosage form of formula ##STR22## wherein R 1 is H, C 1 -C 6 linear or branched alkyl, loweralkenyl, lower alkynyl, --X 12 COOR 6 , --X 11 cycloloweralkyl, --X 12 NR 4 R 5 , X 12 CONR 4 R 5 , --X 12 CN, or --X 11 CX 3 10 ; R 2 is H, loweralkyl, substituted or unsubstituted phenyl wherein the substituents may be 1 or 2 of halo, loweralkyl, loweralkoxy, loweralkylthio, carboxyl, carboxyloweralkyl, nitro, --CF 3 , or hydroxy), 2-, 3-, 4-pyridyl, ##STR23## wherein R 4 and R 5 are independently R 6 or in combination with the N of the NR 4 R 5 group form an unsubstituted or mono or disubstituted, saturated or unsaturated, 4-7 membered heterocyclic ring or benzofused 4-7 membered heterocyclic ring, or said heterocyclic ring or said benzofused heterocyclic ring which further comprises a second heteroatom selected from O and NCH 3 and the substituent(s) is/are independently selected from C 1-4 alkyl; R 6 is H, loweralkyl, cycloloweralkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted phenylloweralkyl wherein the phenyl or phenylloweralkyl substituents may be 1 or 2 of halo, loweralkyl, loweralkoxy, nitro, or CF 3 ; R 7 and R a 7 are independently α- or β-naphthyl, substituted or unsubstituted phenyl wherein the substituents may be 1 or 2 of halo, --NO 2 , --OH, --X 11 R 4 R 5 , loweralkyl, CF 3 , CN, SCF 3 , C⊚CH, CH 2 SCF 3 , ##STR24## OCHF 2 , SH, SPh, PO 3 H-loweralkoxy, or loweralkylthio, COOH, 2-, 3-, 4-pyridyl, ##STR25## R 8 is H, loweralkyl, cycloloweralkyl, --X 12 CONH 2 , --X 12 COOR 6 , --X 12 -cycloloweralkyl, --X 12 NR 4 R 5 , ##STR26## R 9 and R 10 are independently H, --OH, or --CH 3 ; R 11 and R 12 are independently loweralkyl or cycloloweralkyl; R 13 is H, loweralkyl, acyl, O, cycloloweralkyl; R 14 is loweralkyl or phenylloweralkyl; R 15 is H, loweralkyl, ##STR27## or --NH 2 ; R 18 is H, loweralkyl, or acyl; p is O when its adjacent═is unsaturated and 1 when its adjacent═is saturated except that when R 13 is O, p=1, and═is unsaturated; q is 0 to 4; r is 1 or 2; X 1 is H, --NO 2 , CF 3 , CN, OH, loweralkyl, halo, loweralkylthio, loweralkoxy, --X 11 COOR 6 , or --X 11 NR 4 R 5 --; X 2 and X 3 are independently H, --OH, --NO 2 , halo, loweralkylthio, loweralkyl, or loweralkoxy; X 4 is S, O, CH 2 , or NR 18 or NR 8 ; X 5 is H, CF 3 , CN, --COOR 6 , NO 2 , or halo; X 6 is O or HH; X 7 is O, S, HH, or NR 15 ; X 8 is H, loweralkyl; X 9 and X a 9 are independently NR 18 or O; X 10 is F, Cl, or Br; X 11 is absent or C 1-4 linear or branched alkylidene; X 12 is C 1-4 linear or branched alkylidene; --is a saturated or unsaturated bond; or ##STR28## wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , p, q, r, X 1 , X 2 , X 3 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are as defined above, ##STR29## R 7 is α-naphthyl, substituted or unsubstituted phenyl wherein the substituents may be 1 or 2 of halo, --NO 2 , --OH, --X 11 NR 4 R 5 , loweralkyl, CF 3 , CN, SCF 3 , C═CH, CH 2 SCF 3 , ##STR30## OCHF 2 , SH, SPh, PO 3 H, loweralkoxy, loweralkylthio, or COOH, 2-, 3-, 4-pyridyl; ##STR31## R 16 is alpha or beta naphthyl or 2-indolyl; R 18 is H or loweralkyl; and ═ is a saturated or unsaturated bond.

Claim 6

A method for the treatment of idiopathic depression which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a cholecystokinin antagonist or a pharmaceutically acceptable salt thereof in unit dosage form of formula ##STR22## wherein R 1 is H, C 1 -C 6 linear or branched alkyl, loweralkenyl, lower alkynyl, --X 12 COOR 6 , --X 11 cycloloweralkyl, --X 12 NR 4 R 5 , X 12 CONR 4 R 5 , --X 12 CN, or --X 11 CX 3 10 ; R 2 is H, loweralkyl, substituted or unsubstituted phenyl wherein the substituents may be 1 or 2 of halo, loweralkyl, loweralkoxy, loweralkylthio, carboxyl, carboxyloweralkyl, nitro, --CF 3 , or hydroxy), 2-, 3-, 4-pyridyl, ##STR23## wherein R 4 and R 5 are independently R 6 or in combination with the N of the NR 4 R 5 group form an unsubstituted or mono or disubstituted, saturated or unsaturated, 4-7 membered heterocyclic ring or benzofused 4-7 membered heterocyclic ring, or said heterocyclic ring or said benzofused heterocyclic ring which further comprises a second heteroatom selected from O and NCH 3 and the substituent(s) is/are independently selected from C 1-4 alkyl; R 6 is H, loweralkyl, cycloloweralkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted phenylloweralkyl wherein the phenyl or phenylloweralkyl substituents may be 1 or 2 of halo, loweralkyl, loweralkoxy, nitro, or CF 3 ; R 7 and R a 7 are independently α- or β-naphthyl, substituted or unsubstituted phenyl wherein the substituents may be 1 or 2 of halo, --NO 2 , --OH, --X 11 R 4 R 5 , loweralkyl, CF 3 , CN, SCF 3 , C⊚CH, CH 2 SCF 3 , ##STR24## OCHF 2 , SH, SPh, PO 3 H-loweralkoxy, or loweralkylthio, COOH, 2-, 3-, 4-pyridyl, ##STR25## R 8 is H, loweralkyl, cycloloweralkyl, --X 12 CONH 2 , --X 12 COOR 6 , --X 12 -cycloloweralkyl, --X 12 NR 4 R 5 , ##STR26## R 9 and R 10 are independently H, --OH, or --CH 3 ; R 11 and R 12 are independently loweralkyl or cycloloweralkyl; R 13 is H, loweralkyl, acyl, O, cycloloweralkyl; R 14 is loweralkyl or phenylloweralkyl; R 15 is H, loweralkyl, ##STR27## or --NH 2 ; R 18 is H, loweralkyl, or acyl; p is O when its adjacent═is unsaturated and 1 when its adjacent═is saturated except that when R 13 is O, p=1, and═is unsaturated; q is 0 to 4; r is 1 or 2; X 1 is H, --NO 2 , CF 3 , CN, OH, loweralkyl, halo, loweralkylthio, loweralkoxy, --X 11 COOR 6 , or --X 11 NR 4 R 5 --; X 2 and X 3 are independently H, --OH, --NO 2 , halo, loweralkylthio, loweralkyl, or loweralkoxy; X 4 is S, O, CH 2 , or NR 18 or NR 8 ; X 5 is H, CF 3 , CN, --COOR 6 , NO 2 , or halo; X 6 is O or HH; X 7 is O, S, HH, or NR 15 ; X 8 is H, loweralkyl; X 9 and X a 9 are independently NR 18 or O; X 10 is F, Cl, or Br; X 11 is absent or C 1-4 linear or branched alkylidene; X 12 is C 1-4 linear or branched alkylidene; --is a saturated or unsaturated bond; or ##STR28## wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , p, q, r, X 1 , X 2 , X 3 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are as defined above, ##STR29## R 7 is α-naphthyl, substituted or unsubstituted phenyl wherein the substituents may be 1 or 2 of halo, --NO 2 , --OH, --X 11 NR 4 R 5 , loweralkyl, CF 3 , CN, SCF 3 , C═CH, CH 2 SCF 3 , ##STR30## OCHF 2 , SH, SPh, PO 3 H, loweralkoxy, loweralkylthio, or COOH, 2-, 3-, 4-pyridyl; ##STR31## R 16 is alpha or beta naphthyl or 2-indolyl; R 18 is H or loweralkyl; and ═ is a saturated or unsaturated bond.

Claim 10

A method for the treatment of idiopathic depression which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a cholecystokinin antagonist or a pharmaceutically acceptable salt thereof in unit dosage form selected from 1-pyrazolidinecarboxamide, N-(4-bromophenyl)-3-oxo-4,5-diphenyl-, trans-; 1-pyrazolidinecarboxamide, 5-(2-chlorophenyl)-3-oxo-4-phenyl-N-[4-trifluoromethyl)phenyl]-, trans-; and 1-pyrazolidinecarboxamide, N-(4-bromophenyl)-5-(2-chlorophenyl)-3-oxo-4-phenyl-, trans-.

Claim 11

A method for the treatment of idiopathic depression which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a cholecystokinin antagonist or a pharmaceutically acceptable salt thereof in unit dosage form selected from 1-pyrazolidinecarboxamide, N-(4-bromophenyl)-3-oxo-4,5-diphenyl-, trans-; 1-pyrazolidinecarboxamide, 5-(2-chlorophenyl)-3-oxo-4-phenyl-N-[4-trifluoromethyl)phenyl]-, trans-; and 1-pyrazolidinecarboxamide, N-(4-bromophenyl)-5-(2-chlorophenyl)-3-oxo-4-phenyl-, trans-.