Claims
- 1. A compound of the formula: ##STR122## an N-oxide form, a pharmaceutically acceptable salt thereof, or a stereochemically isomeric form thereof, wherein:
- A represents a group of the formula:
- --CH.sub.2 --O-- (a-4),
- --CH.sub.2 --CH.sub.2 --O-- (a-5), or
- --CH.sub.2 --CH.sub.2 --CH.sub.2 --O-- (a-6),
- wherein one or two hydrogen atoms in said groups (a-4) to (a-6) may be replaced by a C.sub.1-6 alkyl group;
- R.sup.1 represents hydrogen, halo, C.sub.1-6 alkylsulfonyl, or aminosulfonyl;
- R.sup.2 represents hydrogen, amino, mono- or di(C.sub.1-6 alkyl)amino, arylC.sub.1-6 alkylamino, or C.sub.1-6 alkylcarbonylamino;
- R.sup.3 and R.sup.4 each independently represent hydrogen or C.sub.1-6 alkyl; and
- L represents a group of the formula:
- --Alk--R.sup.5 (b- 1); or
- --Alk--X--R.sup.6 (b- 2);
- wherein:
- each Alk represents C.sub.1-6 alkanediyl;
- R.sup.5 and R.sup.6 represent Het; and
- X represents O, S, SO.sup.2, or NR.sup.7 wherein R.sup.7 represents hydrogen, C.sub.1-6 alkyl, or aryl;
- wherein in the foregoing:
- Het represents a group of the formula: ##STR123## wherein: X.sup.3 represent O or S;
- R.sup.14 represents hydrogen, C.sub.1-6 alkyl or arylC.sub.1-6 alkyl;
- R.sup.15 represents hydrogen, halo, C.sub.1-6 alkyl or aryl;
- G.sup.1 represents --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--, --N.dbd.N--, or --CO--CH.sub.2 --, wherein one or two hydrogen atoms each independently may be replaced by C.sub.1-6 alkyl;
- G.sup.2 represents --CH.sub.2 --CH.sub.2 --or --CH.sub.2 --N(R.sup.14)--, wherein R.sup.14 is as defined above and wherein one or two hydrogen atoms each independently may be replaced by C.sub.1-6 alkyl; and
- aryl represents phenyl or phenyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, aminosulfonyl, C.sub.1-6 alkylcarbonyl, nitro, trifluoromethyl, amino, and aminocarbonyl.
- 2. A compound according to claim 1 wherein R.sup.1 represents hydrogen or halo, R.sup.2 represents hydrogen or amino, R.sup.3 represents hydrogen or C.sub.1-4 alkyl, and R.sup.4 represents hydrogen.
- 3. A compound according to claim 1 wherein the substituents on the 3 and 4 position of the piperidine ring have the cis-configuration.
- 4. A compound according to claim 1 wherein R.sup.1 is halo, R.sup.2 is amino, R.sup.3 is C.sub.1-4 alkyl, R.sup.4 is hydrogen.
- 5. A pharmaceutical composition comprising an inert carrier and as active ingredient a gastrointestinal motility stimulating amount of a compound as claimed in any of claims 1-4.
- 6. A method of treating warm-blooded animals suffering from a decreased peristalsis of the gastrointestinal system, which method comprises the systemic administration to said warm blooded animals of an effective gastrointestinal stimulating amount of a compound as claimed in any of claims 1-4.
- 7. A compound of the formula: ##STR124## an N-oxide form, a pharmaceutically acceptable salt thereof, or a stereochemically isomeric form thereof, wherein:
- A represents a group of the formula:
- --CH.sub.2 --O-- (a-4),
- --CH.sub.2 --CH.sub.2 --O-- (a-5), or
- --CH.sub.2 --CH.sub.2 --CH.sub.2 --O-- (a-6),
- wherein one or two hydrogen atoms in said groups (a-4) to (a-6) may be replaced by a C.sub.1-6 alkyl group;
- R.sup.1 represents hydrogen, halo, C.sub.1 alkylsulfonyl, or aminosulfonyl;
- R.sup.2 represents hydrogen, amino, mono- or di(C.sub.1-6 alkyl) amino, arylC.sub.1-6 alkylamino, or C.sub.1-6 alkylcarbonylamino;
- R.sup.3 and R.sup.4 each independently represent hydrogen or C.sub.1-6 alkyl; and
- L represents a group of the formula:
- --Alk--R.sup.5 (b- 1); or
- --Alk--X--R.sup.6 (b- 2);
- wherein:
- each Alk represents C.sub.1-6 alkanediyl;
- R.sup.5 and R.sup.6 represent Het; and
- X represents O, S, SO.sup.2, or NR.sup.7 wherein R.sup.7 represents hydrogen, C.sub.1-6 alkyl, or aryl;
- wherein in the foregoing:
- Het represents a group of the formula: ##STR125## wherein: X.sup.3 represent O or S;
- R.sup.14 represents hydrogen, C.sub.1-6 alkyl or arylC.sub.1-6 alkyl;
- G.sup.1 represents --CH.sub.2 --CH.sub.2 --CH.sub.2 --, wherein one or two hydrogen atoms each independently may be replaced by C.sub.1-6 alkyl; and
- aryl represents phenyl or phenyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, aminosulfonyl, C.sub.1-6 alkylcarbonyl, nitro, trifluoromethyl, amino, and aminocarbonyl.
- 8. A compound according to claim 7 wherein R.sup.1 represents hydrogen or -halo, R.sup.2 represents hydrogen or amino, R.sup.3 represents hydrogen or C.sub.1-4 alkyl, and R.sup.4 represents hydrogen.
- 9. A compound according to claim 7 where in the substituents on the 3 and 4 position of the piperidine ring have the cis-configuration.
- 10. A compound according to claim 7 wherein R.sup.1 is halo, R.sup.2 is amino, R.sup.3 is C.sub.1-4 alkyl, R.sup.4 is hydrogen.
- 11. A pharmaceutical composition comprising an inert carrier and as active ingredient a gastrointestinal motility stimulating amount of a compound as claimed in any of claims 7-10.
- 12. A method of treating warm-blooded animals suffering from a decreased peristalsis of the gastrointestinal system, which method comprises the systemic administration to said warm blooded animals of an effective gastrointestinal stimulating amount of a compound as claimed in any of claims 7-10.
- 13. A compound of the formula: ##STR126## an N-oxide form, a pharmaceutically acceptable salt thereof, or a stereochemically isomeric form thereof, wherein:
- A represents a group of the formula:
- --CH.sub.2 --O-- (a-4),
- --CH.sub.2 --CH.sub.2 --O-- (a-5), or
- --CH.sub.2 --CH.sub.2 --CH.sub.2 --O-- (a-6),
- wherein one or two hydrogen atoms in said groups (a-4) to (a-6) may be replaced by a C.sub.1-6 alkyl group;
- R.sup.1 represents hydrogen, halo, C.sub.1-6 alkylsulfonyl, or aminosulfonyl;
- R.sup.2 represents hydrogen, amino, mono- or di(C.sub.1-6 alkyl) amino, arylC.sub.1-6 alkylamino, or C.sub.1-6 alkylcarbonylamino;
- R.sup.3 and R.sup.4 each independently represent hydrogen or C.sub.1-6 alkyl; and
- L represents a group of the formula:
- --Alk--R.sup.5 (b- 1); or
- --Alk--X--R.sup.6 (b- 2);
- wherein:
- each Alk represents C.sub.1-6 alkanediyl;
- R.sup.5 and R.sup.6 represent Het; and
- X represents O, S, SO.sup.2, or NR.sup.7 wherein R.sup.7 represents hydrogen, C.sub.1-6 alkyl, or aryl;
- wherein in the foregoing:
- Het represents a group of the formula: ##STR127## wherein: G.sup.2 represents --CH.sub.2 --CH.sub.2 --CH.sub.2 --, wherein one or two hydrogen atoms each independently may be replaced by C.sub.1-6 alkyl; and
- aryl represents phenyl or phenyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, aminosulfonyl, C.sub.1-6 alkylcarbonyl, nitro, trifluoromethyl, amino, and aminocarbonyl.
- 14. A compound according to claim 13 wherein R.sup.1 represents hydrogen or halo, R.sup.2 represents hydrogen or amino, R.sup.3 represents hydrogen or C.sub.1-4 alkyl, and R.sup.4 represents hydrogen.
- 15. A compound according to claim 13 wherein the substituents on the 3 and 4 position of the piperidine ring have the cis-configuration.
- 16. A compound according to claim 13 wherein R.sup.1 is halo, R.sup.2 is amino, R.sup.3 is C.sub.1-6 alkyl, R.sup.4 is hydrogen.
- 17. A pharmaceutical composition comprising an inert carrier and as active ingredient a gastrointestinal motility stimulating amount of a compound as claimed in any of claims 13-16.
- 18. A method of treating warm-blooded animals suffering from a decreased peristalsis of the gastrointestinal system, which method comprises the systemic administration to said warm blooded animals of an effective gastrointestinal stimulating amount of a compound as claimed in any of claims 13-16.
- 19. A compound of the formula: ##STR128## an N-oxide form, a pharmaceutically acceptable salt thereof, or a stereochemically isomeric form thereof, wherein:
- A represents a group of the formula:
- --CH.sub.2 --O-- (a-4),
- --CH.sub.2 --CH.sub.2 --O-- (a-5), or
- --CH.sub.2 --CH.sub.2 --CH.sub.2 --O-- (a-6),
- wherein one or two hydrogen atoms in said groups (a-4) to (a-6) may be replaced by a C.sub.1-6 alkyl group;
- R.sup.1 represents hydrogen, halo, C.sub.1-6 alkylsulfonyl, or aminosulfonyl;
- R.sup.2 represents hydrogen, amino, mono- or di(C.sub.1-6 alkyl) amino, arylC.sub.1-6 alkylamino, or C.sub.1-6 alkylcarbonylamino;
- R.sup.3 and R.sup.4 each independently represent hydrogen or C.sub.1-6 alkyl; and
- L represents a group of the formula:
- --Alk--R.sup.5 (b- 1); or
- --Alk--X--R.sup.6 (b- 2);
- wherein:
- each Alk represents C.sub.1-6 alkanediyl;
- R.sup.5 and R.sup.6 represent Het; and
- X represents O, S, SO.sup.2, or NR.sup.7 wherein R.sup.7 represents hydrogen, C.sub.1-6 alkyl, or aryl;
- wherein in the foregoing:
- Het represents a group of the formula: ##STR129## wherein: represents hydrogen, halo, C.sub.1-6 alkyl or aryl; and
- aryl represents phenyl or phenyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, aminosulfonyl, C.sub.1-6 alkylcarbonyl, nitro, trifluoromethyl, amino, and aminocarbonyl.
- 20. A compound according to claim 19 wherein R.sup.1 represents hydrogen or halo, R.sup.2 represents hydrogen or amino, R.sup.3 represents hydrogen or C.sub.1-4 alkyl, and R.sup.4 represents hydrogen.
- 21. A compound according to claim 19 wherein the substituents on the 3 and 4 position of the piperidine ring have the cis-configuration.
- 22. A compound according to claim 19 wherein R.sup.1 is halo, R.sup.2 is amino, R.sup.3 is C.sub.1-4 alkyl, R.sup.4 is hydrogen.
- 23. A pharmaceutical composition comprising an inert carrier and as active ingredient a gastrointestinal motility stimulating amount of a compound as claimed in any of claims 19-22.
- 24. A method of treating warm-blooded animals suffering from a decreased peristalsis of the gastrointestinal system, which method comprises the systemic administration to said warm blooded animals of an effective gastrointestinal stimulating amount of a compound as claimed in any of claims 19-22.
- 25. A compound of the formula: ##STR130## an N-oxide form, a pharmaceutically acceptable salt thereof, or a stereochemically isomeric form thereof, wherein:
- A represents a group of the formula:
- --CH.sub.2 --O-- (a-4),
- --CH.sub.2 --CH.sub.2 --O-- (a-5), or
- --CH.sub.2 --CH.sub.2 --CH.sub.2 --O-- (a-6),
- wherein one or two hydrogen atoms in said groups (a-4) to (a-6) may be replaced by a C.sub.1-6 alkyl group;
- R.sup.1 represents hydrogen, halo, C.sub.1-6 alkylsulfonyl, or aminosulfonyl;
- R.sup.2 represents hydrogen, amino, mono- or di(C.sub.1-6 alkyl) amino, arylC.sub.1-6 alkylamino, or C.sub.1-6 alkylcarbonylamino;
- R.sup.3 and R.sup.4 each independently represent hydrogen or C.sub.1-6 alkyl; and
- L represents a group of the formula:
- --Alk--R.sup.5 (b- 1); or
- --Alk--X--R.sup.6 (b- 2);
- wherein:
- each Alk represents C.sub.1-6 alkanediyl;
- R.sup.5 and R.sup.6 represent Het; and
- X represents O, S, SO.sup.2 or NR.sup.7 wherein R.sup.7 represents hydrogen, C.sub.1-6 alkyl, or aryl;
- wherein in the foregoing:
- Het represents a group of the formula: ##STR131## and aryl represents phenyl or phenyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halo, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, aminosulfonyl, C.sub.1-6 alkylcarbonyl, nitro, trifluoromethyl, amino, and aminocarbonyl.
- 26. A compound according to claim 25 wherein R.sup.1 represents hydrogen or halo, R.sup.2 represents hydrogen or amino, R.sup.3 represents hydrogen or C.sub.1-4 alkyl, and R.sup.4 represents hydrogen.
- 27. A compound according to claim 25 wherein the substituents on the 3 and 4 position of the piperidine ring have the cis-configuration.
- 28. A compound according to claim 25 wherein R.sup.1 is halo, R.sup.2 is amino, R.sup.3 is C.sub.1-4 alkyl, R.sup.4 is hydrogen.
- 29. A pharmaceutical composition comprising an inert carrier and as active ingredient a gastrointestinal motility stimulating amount of a compound as claimed in any of claims 25-28.
- 30. A method of treating warm-blooded animals suffering from a decreased peristalsis of the gastrointestinal system, which method comprises the systemic administration to said warm blooded animals of an effective gastrointestinal stimulating amount of a compound as claimed in any of claims 25-28.
CROSS-REFERENCE TO RELATED APPLICATION
This is a division of application Ser. No. 08/301,825, filed Sep. 7, 1994, now U.S. Pat. No. 5,552,553 which was a division of application Ser. No. 07/489,419, filed Mar. 6, 1990, now U.S. Pat. No. 5,374,637, which was a continuation-in-part of application Ser. No. 07/326,941, filed Mar. 22, 1989, now abandoned.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4434170 |
Dostert et al. |
Feb 1984 |
|
4772459 |
Sun et al. |
Sep 1988 |
|
Foreign Referenced Citations (8)
Number |
Date |
Country |
68700 |
Jan 1983 |
EPX |
76530 |
Apr 1983 |
EPX |
124783 |
Nov 1984 |
EPX |
147044 |
Jul 1985 |
EPX |
234872 |
Sep 1987 |
EPX |
299566 |
Jan 1989 |
EPX |
309043 |
Mar 1989 |
EPX |
307172 |
Mar 1989 |
EPX |
Divisions (2)
|
Number |
Date |
Country |
Parent |
301825 |
Sep 1994 |
|
Parent |
489419 |
Mar 1990 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
326941 |
Mar 1989 |
|