Claims
- 1. A method of treating warm-blooded animals suffering from diarrhea, which method comprises the systemic administration to warm-blooded animals of an amount effective in treating diarrhea of a compound having the formula: ##STR22## an N-oxide form, a pharmaceutically acceptable acid-solution salt, or a possible stereoisomeric form thereof, wherein
- R.sup.1 is a member selected from the group consisting of hydrogen, C.sub.1-6 alkyl, aryl C.sub.1-6 alkyl; C.sub.1-6 alkylcarbonyl, aminoC.sub.1-6 alkyl, and mono- and di(C.sub.1-6 alkyl)aminoC.sub.1-6 alkyl;
- R.sup.2 is a member selected from the group consisting of hydrogen and C.sub.1-6 alkyl;
- Ar is a radical of the formula; ##STR23## wherein R.sup.3, R.sup.4, and R.sup.5 are each independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, halo, hydroxy, cyano, nitro, amino, mono- and di(C.sub.1-6 alkyl)amino, aminocarbonyl, arylcarbonylamino, C.sub.1-6 alkylcarbonylamino, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkylcarbonyloxy, aminosulfonyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl, CI-6 alkylthio, mercapto, C3-6 alkynyloxy, C3-6 alkenyloxy, aryl C.sub.1-6 alkyloxy, aryloxy, and C.sub.1-6 alkyl substituted with up to 4 halo atoms;
- Alk is --CH.sub.2 --CH.sub.2 - or --CH.sub.2 --CH(CH.sub.3)--;
- Ar.sup.1 and Ar.sup.2 are, each independently, phenyl or halophenyl;
- R.sup.6 and R.sup.7 are each independently hydrogen, C.sub.1-6 alkyl, phenylmethyl, or 2-propenyl;
- wherein aryl is member selected from the group consisting of phenyl being optionally substituted with up to 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, aminocarboxyl, and phenylcarbonyl, said phenylcarbonyl being optionally substituted with up to 3 halo atoms.
- 2. A method according to claim 1 wherein the active compound is a compound of formula (I) wherein the substituents in the 3- and 4-position of the piperidine ring have the trans configuration.
- 3. A method according to claim 2 wherein Ar is a radical of formula (a-1) wherein R.sup.3 is arylC.sub.1-6 alkyloxy, aryloxy, C.sub.3-6 alkenyloxy, C.sub.3-6 alkynyloxy, and C.sub.1-4 alkyl substituted with up to 4 halo atoms, and R.sup.4 and R.sup.5 are each independently selected from the group consisting of hydrogen, C.sub.1-6 alkylC.sub.1-6 alkyloxy, halo, hydroxy, cyano, nitro, amino, mono- and di(C.sub.1-6 alkyl)amino, aminocarbonyl, arylcarbonylamino, C.sub.1-6 alkylcarbonylamino, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkylcarbonyloxy, aminosulfonyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl, C.sub.1-6 alkylthio, mercapto, aryl C.sub.1-6 alkyloxy, aryloxy, C.sub.3-6 alkenyloxy, C.sub.3-6 alkynyloxy, and C.sub.1-6 alkyl substituted with up to 4 halo atoms.
- 4. A method according to claim 2 wherein Ar is a radical of formula (a-1) wherein R.sup.3, R.sup.4, and R.sup.5 are each independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, halo, hydroxy, cyano, nitro, amino, mono- and di((C.sub.1-6 alkyl)amino, aminocarbonyl, arylcarbonylamino, C.sub.1-6 alkylcarbonylamino C.sub.1-6 alkycarbonyl, C.sub.1-6 alkylcarbonyloxy, aminosulfonyl, C.sub.1-6 alkylsulfinyl C.sub.1-6 alkylsulfonyl C.sub.1-6 alkylthio, and mercapto.
- 5. A method according to claim 3 wherein Ar is a radical of formula (a-1) wherein R.sup.3 is phenylmethoxy, phenyloxy, propenyloxy, or C.sub.1-4 alkyl substituted with up to 4 halo substituents, and R.sup.4 and R.sup.5 are each independently hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkyloxy, halo, hydroxy, nitro, amino, phenylmethoxy, phenoxy, propenyloxy, or C.sub.1-4 alkyl substituted with up to 4 halo atoms; R.sup.1 is hydrogen or C.sub.1-4 alkyl; and R.sup.6 and R.sup.7 are each independently hydrogen, C.sub.1-4 alkyl, phenylmethyl, or 2-propenyl.
- 6. A method according to claim 5 wherein Ar is a radical of formula (a-1) wherein R.sup.3 is trifluoromethyl substituted on the meta position and R.sup.4 and R.sup.5 are each independently hydrogen, methyl, methoxy, halo, hydroxy, nitro, amino, trifluoromethyl, phenylmethoxy, phenoxy, or propenyloxy.
- 7. A method according to claim 1, wherein R.sup.3 is C.sub.1-6 alkyl substituted with 1-4 halo atoms.
- 8. An anti-diarrheal composition comprising an inert carrier and as an active ingredient an anti-diarrheal amount of at least one compound having the formula: ##STR24## an N-oxide form, a pharmaceutically acceptable acid-addition salt, or a possible stereoisomeric form thereof, wherein
- R.sup.1 is a member selected from the group consisting of hydrogen, C.sub.1-6 alkyl, acryl C.sub.1-6 alkyl, C.sub.1-6 alkylcarbonyl, amino C.sub.1-6 alkyl, and mono- and di-(C.sub.1-6 alkyl)amino C.sub.1-6 alkyl;
- R.sup.2 is a member selected from the group consisting of hydrogen and C.sub.1-6 alkyl;
- Ar is a radical of the formula: ##STR25## wherein R.sup.3, is aryl C.sub.1-6 alkyloxy, aryloxy, C.sub.3-6 alkenyloxy, C.sub.3-6 alkynyloxy, or C.sub.1-5 alkyl substituted with 1-4 halo atoms, and R.sup.4 and R.sup.5 are each independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, halo, hydroxy, cyano, nitro, amino, mono- and di (C.sub.1-6 alkyl)amino, aminocarbonyl, arylcarbonylamino, C.sub.1-6 alkylcarbonylamino, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkylcarbonyloxy, aminosulfonyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl, C.sub.1-6 alkylthio, mercapto, C.sub.3-6 alkylnyloxy, C.sub.3-6 alkenyloxy, aryl C.sub.1-6 alkyloxy, aryloxy, and C.sub.1-6 alkyl substituted with up to 4 halo atoms;
- Alk is --CH.sub.2 --CH.sub.2 --or --CH.sub.2 --CH(CH.sub.3)--;
- Ar.sup.1 and Ar.sup.2 are each independently phenyl or halophenyl;
- R.sup.6 and R.sup.7 are each independently hydrogen, C.sub.1-6 alkyl, phenylmethyl, or 2-propenyl;
- wherein aryl is a member selected from the group consisting of phenyl being optionally substituted with up to 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, aminocarbonyl and phenylcarbonyl, said phenylcarbonyl being optionally substituted with up to 3 halo atoms.
- 9. An anti-diarrheal composition according to claim 8 wherein the active compound is a compound of formula (I) wherein the substituents in the 3- and 4-position of the piperidine ring have the trans configuration.
- 10. An anti-diarrheal composition according to claim 9 wherein Ar is a radical of formula (a-2) wherein R.sup.4 and R.sup.5 are each independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, halo, hydroxy, cyano, nitro, amino, mono- and di(C.sub.1-6 alkyl) amino, aminocarbonyl, arylcarbonylamino, C.sub.1-6 alkylcarbonylamino, C.sub.1-6 aIkylcarbonyl, C.sub.1-6 alkylcarbonyloxy, aminosulfonyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl, C.sub.1-6 alkylthio, and mercapto.
- 11. An anti-diarrheal composition according to claim 9 wherein Ar is a radical of formula (a-2) wherein R.sup.3 is phenylmethoxy, phenyloxy, propenyloxy, or C.sub.1-4 alkyl substituted with up to 4 halo substituents; R.sup.4 and R.sup.5 are each independently hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkyloxy, halo, hydroxy, nitro, amino, phenylmethoxy, phenoxy, propenyloxy, or C.sub.1-4 alkyl substituted with up to 4 halo atoms; R.sup.1 is hydrogen or C.sub.1-4 alkyl; and R.sup.6 and R.sup.7 are each independently hydrogen, C.sub.1-4 alkyl, phenylmethyl, or 2-propenyl.
- 12. An anti-diarrheal composition according to claim 11 wherein Ar is a radical of formula (a-2) wherein R.sup.3, is trifluoromethyl substituted on the meta position, and R.sup.4 and R.sup.5 are each independently hydrogen, methyl, methoxy, halo, hydroxy, nitro, amino, trifluoromethyl, phenylmethoxy, phenoxy, or propenyloxy.
- 13. An anti-diarrheal composition according to claim 8 wherein the compound is that wherein R.sup.3' is C.sub.1-6 alkyl substituted with 1-4 halo atoms.
- 14. A method according to claim 1 wherein the compound is trans-3-hydroxy-N,N,.gamma.-trimethyl-.alpha..alpha.-diphenyl-4-[[3-(trifluoromethyl)-benzoyl]amino]-1-piperidinebutanamide.
- 15. An anti-diarrheal composition according to claim 8 wherein the compound is trans-3-hydroxy-N,N,.gamma.-trimethyl-.alpha.,.alpha.-diphenyl-4-[[3-(trifluoromethyl)benzoyl]amino]-1-piperidinebutanamide.
CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation of application Ser. No. 57,451, filed May 26, 1987, which is a continuation-in-part of our co-pending application Ser. No. 882,067, filed July 3, 1986, now abandoned.
US Referenced Citations (4)
Number |
Name |
Date |
Kind |
3647805 |
Irikura et al. |
Mar 1972 |
|
3714159 |
Janssen et al. |
Jan 1973 |
|
4069331 |
Langbein et al. |
Jan 1978 |
|
4138492 |
Noverola et al. |
Feb 1979 |
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
76530 |
Dec 1985 |
EPX |
Non-Patent Literature Citations (1)
Entry |
Chemical Abstracts, vol. 99 (1983), 194812d. |
Continuations (1)
|
Number |
Date |
Country |
Parent |
57451 |
May 1987 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
882067 |
Jul 1986 |
|