Substituted 4-aminoquinoline derivatives as gastric acid secretion inhibitors

{
  "publication_number": "US5082848A",
  "country": "US",
  "kind": "A",
  "title": "Substituted 4-aminoquinoline derivatives as gastric acid secretion inhibitors",
  "abstract": "Substituted 4-aminoquinoline derivatives of the formula: ##STR1## wherein R 1 is hydrogen, C 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl; C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-6 alkyl, phenyl C 1-6 alkyl, the phenyl groups being optionally substituted; R 2 is hydroxy C 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl or two adjacent groups R 2 together form a C 1-4 alkylenedioxy group; R 3 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, amino, C 1-6 alkylthio, halogen, cyano, hydroxy, C1-6alkanoyl, or trifluromethyl; R 4 is hydrogen, C 1-6 alkyl, phenyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkanoyl, amino, C 1-6 alkylamino, di- C 1-6 alkyl amino, halogen, or trifluromethyl; n is 1 or 2; q is 0 to 4; m is 1, 2, or 3; and p is 1, 2, 3, or 4 provided that m+p is not greater than 5; or a salt thereof are useful as inhibitors of gastric acid secretion.",
  "claims": [
    "1. A compound of the structure (I): ##STR8## wherein R 1 is hydrogen, C 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-6 alkyl, phenyl, phenyl C 1-6 alkyl, the phenyl groups being optionally substituted by 1 to 3 substituents selected from C 1-6 alkyl, C 1-6 alkoxy, amino, C 1-6 alkylthio, halogen, hydroxy, carbamoyl, carboxy, C 1-6 alkanoyl, trifluoromethyl or cyano; R 2 is hydroxyC 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl or two adjacent R 2 groups together form a C 1-4 alkylenedioxy group; R 3 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, amino, C 1-6 alkylthio, halogen, cyano, hydroxy, C1-6alkanoyl, or trifluoromethyl; R 4 is hydrogen, C 1-6 alkyl, phenyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkanoyl, amino, C 1-6 alkylamino, di-C 1-6 alkyl amino, halogen, or trifluromethyl; n is 1 or 2; q is 0 or 4; m is 1, 2, or 3; and p is 1, 2, 3, or 4 provided that m+p is not greater than 5; or a salt thereof.",
    "2. A compound according to claim 1 in which m is 1 and R 2 is in the 2-position of the phenyl ring.",
    "3. A compound according to claim 1 or 2 in which the group R 4 is a C 1-6 alkyl or C 1-6 alkoxy group in the 8-position of the quinoline ring.",
    "4. A compound according to claim 1 which is 3-butyryl-4-(2-(hydroxymethyl)phenylamino)-8-methoxyquinoline.",
    "5. A compound according to claim 1 which is 3-butyryl-4-(2-methoxymethylphenylamino)-8-methoxyquinoline.",
    "6. A compound according to claim 1 which is 3-butyryl-4-(3,4-(methylenedioxy)phenyl-amino)-8-methoxyquinoline.",
    "7. A compound according to claim 1 which is 3-butyryl-4-(4-hydroxymethylphenylamino)-8-methoxyquinoline.",
    "8. A compound according to claim I which is 3-butyryl-4-(3,4-methylenedioxy-2,6-dimethylphenylamino)8-methoxyquinoline",
    "9. A compound according to claim 1 which is 3-butyryl-4-(3-hydroxymethyl-2-methylphenylamino)-8-methoxyquinoline.",
    "10. A compound according to claim 1 which is 3-butyryl-4-(5-hydroxymethyl-2-methylphenylamino)-8-methoxyquinoline.",
    "11. A pharmaceutical composition comprising a compound according to claim I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.",
    "12. A method of inhibiting gastric acid secretion which comprises administering to a mammal in need thereof an effective amount of a compound according to claim I.",
    "13. A method of treatment of gastrointestinal diseases and other conditions caused or exacerbated by gastric acidity which comprises administering to a mammal in need thereof an effective amount of a compound according to claim 1.",
    "14. A compound of structure (IV) ##STR9## wherein R 1 is hydrogen, C 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 cycloalkyl-C 1-6 alkyl, phenyl, phenylC 1-6 alkyl, the phenyl groups being optionally substituted by 1 to 3 substituents selected from C 1-6 alkyl, C 1-6 alkoxy, amino, C 1-6 alkylthio, halogen, hydroxy, carbamoyl, carboxy, C 1-6 alkanoyl, trifluromethyl or cyano; R 2 is hydroxyC 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl, or two adjacent groups R 2 together form a C 1-4 alkylenedioxy group; R 3 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, amino, C 1-6 alkylthio, halogen, cyano, hydroxy, C 1-6 alkanoyl, or trifluoromethyl; R 4 is hydrogen, C 1-6 alkyl, phenyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkanoyl, amino, C 1-6 alkylamino, di-C 1-6 alkylamino, halogen, or trifluromethyl; n is 1 or 2; q is 0 to 4; m is 1, 2, or 3; p is 1, 2, 3 or 4 provided that m+p is not greater than 5; and R 5 is hydrogen or a nitrogen protecting group.",
    "15. A compound of structure (V) ##STR10## wherein R 1' is hydrogen, C 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 cycloalkyl-C 1-6 alkyl, phenyl, phenylC 1-6 alkyl, the phenyl groups being optionally substituted to 1 to 3 substituents selected from C 1-6 alkyl, C 1-6 alkoxy, amino, C 1-6 alkylthio, halogen, cyano, hydroxy, carbamoyl, carboxy, C 1-6 alkanoyl, trifluoromethyl or: R 3 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, amino, C 1-6 alkylthio, halogen, cyano, hydroxy, C 1-6 alkanoyl, or trifluoromethyl: R 4 is hydrogen, C 1-6 alkyl, phenyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkanoyl, amino, C 1-6 alkylamino, di-C 1-6 alkylamino, halogen, or trifluoromethyl: n is 1 or 2; q is 0 to 4; m is 1, 2, or 3; p is 1, 2, 3 or 4 provided that m+p is not greater than 5; R 5 is hydrogen or a nitrogen protecting group; R 2' is an optionally protected group R 2; and R 2 is hydroxyC 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl, or two adjacent groups R 2 together form a C 1-4 alkylenedioxy group;",
    "16. The compound according to claim 1 wherein q is 0.",
    "17. The compound according to claim 16 wherein R 2 is hydroxy C 1-6 alkyl.",
    "18. The compound according to claim 16 wherein R 2 is C 1-6 alkoxy C 1-6 alkyl.",
    "19. The compound according to claim 16 wherein R 2 is C 1-4 alkylenedioxy.",
    "20. The compound according to claim 17 wherein R 2 is hydroxymethyl.",
    "21. The compound according to claim 17 wherein R 2 is methoxymethyl."
  ],
  "cpc": [
    "C07D 405/12",
    "A61P 1/04",
    "C07D 215/42",
    "C07D 215/44"
  ],
  "assignees": [
    "SMITH KLINE FRENCH LAB"
  ],
  "filing_date": "1989-02-23",
  "publication_date": "1992-01-21",
  "grant_date": "1992-01-21",
  "priority_date": "1988-02-25",
  "application_number": "US-31536989-A",
  "family_id": "10632378",
  "citations": [
    "EP0259174A1",
    "FR2106612A1",
    "GB2047244A",
    "US2652398A",
    "US3470186A",
    "US4343804A",
    "US4806549A",
    "US4806550A"
  ]
}