Claims
- 1. A compound of the formula: ##STR125## 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 C.sub.3-6 cycloalkyl, C.sub.5-6 cycloalkanone, C.sub.3-6 alkenyl optionally substituted with aryl, or L represents a group of the formula:
- --Alk--R.sup.5 (b- 1);
- --Alk--X--R.sup.6 (b- 2);
- --Alk--Y--CO--R.sup.8 (b- 3);
- or
- --Alk--Y--CO--NR.sup.10 R.sup.11 (b- 4),
- wherein:
- each Alk represents C.sub.1-6 alkanediyl;
- R.sup.5 represents hydrogen, cyano, C.sub.1-6 alkylsulfonylamino, C.sub.3-6 cycloalkyl, C.sub.5-6 cycloalkanone, aryl, di(aryl)methyl, or Het;
- R.sup.6 represents hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, aryl or Het;
- X represents O, S, SO.sub.2, or NR.sup.7 wherein R.sup.7 represents hydrogen, C.sub.1-6 alkyl, or aryl;
- R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, aryl, arylC.sub.1-6 alkyl, di (aryl) methyl or C.sub.1-6 alkyloxy;
- Y represents NR.sup.9 or a direct bond, wherein R.sup.9 represents hydrogen, C.sub.1-6 alkyl or aryl;
- each R.sup.10 and R.sup.11 independently represent hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, aryl or arylC.sub.1-6 alkyl; or R.sup.10 and R.sup.11 combined with the nitrogen atom bearing R.sup.10 and R.sup.11 may form a pyrrolidinyl or piperidinyl ring, both being optionally substituted with C.sub.1-6 alkyl, amino or mono- or di(C.sub.1-6 alkyl)amino; or R.sup.10 and R.sup.11 combined with the nitrogen atom bearing R.sup.10 and R.sup.11 may form a piperazinyl or 4-morpholinyl group, both being optionally substituted with C.sub.1-6 alkyl;
- wherein in the foregoing:
- Het represents a group of the formula: ##STR126## wherein each X.sup.1 and X.sup.2 independently represent O or S, m represents 1 or 2, each R.sup.12 independently represents hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkyloxyC.sub.1-4 alkyl, or hydroxyC.sub.1-4 alkyl, and R.sup.13 represents hydrogen, halo, or C.sub.1-4 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, aminosulfony, 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, R.sup.4 represents hydrogen, and:
- L represents a group of formula (b-1) wherein R.sup.5 is hydrogen, C.sub.3-6 cycloalkyl, C.sub.5-6 cycloalkanone, aryl or Het; or
- L represents a group of formula (b-2) wherein X represents O, S, or NH and R.sup.6 is hydrogen, C.sub.1-4 alkyl, aryl or Het; or
- L represents a group of formula (b-3) wherein Y is NH or a direct bond and R.sup.8 is hydrogen, C.sub.1-4 alkyl, aryl or C.sub.1-4 alkyloxy; or
- L represents a group of formula (b-4) wherein Y is NH or a direct bond and R.sup.10 and R.sup.11 each independently are hydrogen, C.sub.1-4 alkyl or aryl, or R.sup.10 and R.sup.11 combined with the nitrogen atom bearing said R.sup.10 and R.sup.11 may form a pyrrolidinyl or piperidinyl group.
- 3. A compound according to claim 2 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, and 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 and 2-4.
- 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 and 2-4.
- 7. A compound as defined in claim 1 wherein said compound is: cis-8-amino-7-chloro-N-[1-[3-(4-fluorophenoxy) propyl ]-3-methoxy4-piperidinyl ]-2,3 -dihydro-1,4 -benzodioxin-5-carboxamide; or a pharmaceutically acceptable salt thereof.
- 8. A pharmaceutical composition comprising an inert carrier and as active ingredient a gastrointestinal motility stimulating amount of a compound as claimed in claim 7.
- 9. 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 claim 7.
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.
Non-Patent Literature Citations (2)
Entry |
E. Eliel "Stereochemistry of Carbon Compounds", McGraw Hill Book Co., New York, pp. 49-50 (1962). |
M. Zanger et al. "Structure-Activity Relationships and Drug Design", Remington's Pharmaceutical Sciences, 16th ed., Philadelphia College of Pharmacy, Philadelphia, pp. 420-435 (1980). |
Divisions (2)
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Number |
Date |
Country |
Parent |
301825 |
Sep 1994 |
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Parent |
489419 |
Mar 1990 |
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Continuation in Parts (1)
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Date |
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326941 |
Mar 1989 |
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