Claims
- 1. A compound of the formula: ##STR19## in which R.sup.1 is alkyl of 1 to 6 carbon atoms;
- R.sup.2 and R.sup.3 are alkyl of 1 to 6 carbon atoms or taken together they are polymethylene of 2 to 12 carbon atoms or taken together with the carbon atom to which they are attached, R.sup.2 and R.sup.3 complete a 5-norbornen-2-yl moiety;
- X is --CO.sub.2 --, --OCO--, --OCO.sub.2 --, --N(R.sup.7)CO--, --NHNHCO--, --ON(R.sup.7)CO--, --CON(R.sup.7)--, --N(R.sup.7)CO.sub.2 --, --OCON(R.sup.7)-- or --N(R.sup.7)CON(R.sup.8)--; wherein R.sup.7 and R.sup.8 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are halo, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, cyano, nitro or perhalomethyl;
- R.sup.4 is hydrogen or alkyl of 1 to 6 carbon atoms;
- R.sup.5 is hydrogen, alkyl of 1 to 8 carbon atoms, hydroxyalkyl of 1 to 3 carbon atoms, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are hydroxy, halo, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, trifluoromethyl, nitro, cyano, carbalkoxy of 2 to 7 carbon atoms, carboxamide, amino, alkylamino of 1 to 6 carbon atoms or dialkylamino of 2 to 12 carbon atoms;
- R.sup.6 is phenyl, benzyl, 2-, 3-, or 4-pyridinyl, 2-pyrimidinyl or 2-pyrazinyl; any of which may be substituted by one or more hydroxy, halo, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, trifluoromethyl, nitro, cyano, carbalkoxy of 2 to 7 carbon atoms, carboxamido, amino, alkylamino of 1 to 6 carbon atoms or dialkylamino of 2 to 12 carbon atoms;
- and
- n is one of the integers 0, 1, 2, 3, 4 or 5; or a pharmaceutically acceptable salt thereof, with the proviso that when X is --CON(R.sup.7)-- and R.sup.7 is alkyl, R.sup.6 is other than 2-pyrimidinyl and when X is --CO.sub.2 -- and R.sup.1, R.sup.2 and R.sup.3 are methyl and n is 1, R.sup.6 is other than 3,5-di(trifluoromethyl)phenyl.
- 2. A compound of claim 1 of the formula: ##STR20## in which R.sup.1 is alkyl of 1 to 6 carbon atoms;
- R.sup.2 and R.sup.3 are alkyl of 1 to 6 carbon atoms or taken together they are polymethylene of 2 to 6 carbon atoms or taken together with the carbon atom to which they are attached, R.sup.2 and R.sup.3 complete a 5-norbornen-2-yl moiety;
- X is --CO.sub.2 --, --OCO--, --OCO.sub.2 --, --N(R.sup.7)CO--, --NHNHCO--, --ON(R.sup.7)CO--, --CON(R.sup.7)--, --N(R.sup.7)CO.sub.2 --, --OCON(R.sup.7)-- or --N(R.sup.7)CON(R.sup.8)--; wherein R.sup.7 and R.sup.8 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substitutents are halo, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, cyano, nitro or perhalomethyl;
- R.sup.4 is hydrogen or alkyl of 1 to 6 carbon atoms;
- R.sup.5 is hydrogen, alkyl of 1 to 6 carbon atoms, hydroxyalkyl of 1 to 3 carbon atoms, phenyl, benzyl, p-hydroxyphenyl, p-methoxyphenyl, o-methoxyphenyl, p-chlorophenyl or p-fluorophenyl;
- R.sup.6 is phenyl, 2-alkylphenyl in which the alkyl substituent has 1 to 6 carbon atoms, 2-alkoxyphenyl in which the alkoxy substituent has 1 to 6 carbon atoms, 2-halophenyl, 2-cyanophenyl, 2-nitrophenyl, 2-perhalomethylphenyl, benzyl, 2-, 3-, or 4-pyridinyl, 2-pyrimidinyl or 2-pyrazinyl;
- and
- n is one of the integers 0, 1, 2, 3, 4 or 5; or a pharmaceutically acceptable salt thereof, with the proviso that when X is --CON(R.sup.7)-- and R.sup.7 is alkyl, R.sup.6 is other than 2-pyrimidinyl.
- 3. A compound of claim 1 in which R.sup.2 and R.sup.3 are, independently, alkyl of 1 to 6 carbon atoms.
- 4. A compound of claim 2 in which R.sup.4 is hydrogen and R.sup.5 is alkyl of 1 to 6 carbon atoms, phenyl or benzyl.
- 5. A compound of claim 2 in which R.sup.6 is 2-methoxyphenyl, 2-chlorophenyl or 2-pyrimidinyl.
- 6. A compound of the formula: ##STR21## in which X is --CO.sub.2 -- or --NHCO.sub.2 --;
- R.sup.6 is 2-, 3- or 4-pyridinyl, 2-pyrimidinyl or 2-pyrazinyl, or a pharmaceutically acceptable salt thereof.
- 7. A compound of the formula: ##STR22## in which R.sup.1 is alkyl of 1 to 6 carbon atoms;
- R.sup.2 and R.sup.3, taken together, are polymethylene of 2 to 12 carbon atoms or taken together with the carbon atom to which they are attached, R.sup.2 and R.sup.3 complete a 5-norbornen-2-yl moiety;
- X is --CO.sub.2 --, --OCO--, --OCO.sub.2 --, --N(R.sup.7)CO--, --NHNHCO--, --ON(R.sup.7)CO--, --CON(R.sup.7)--, --N(R.sup.7)CO.sub.2 --, --OCON(R.sup.7)-- or --N(R.sup.7)CON(R.sup.8)--, wherein R.sup.7 and R.sup.8 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are halo, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, cyano, nitro or perhalomethyl;
- R.sup.4 is hydrogen or alkyl of 1 to 6 carbon atoms;
- R.sup.5 is hydrogen, alkyl of 1 to 8 carbon atoms, hydroxyalkyl of 1 to 3 carbon atoms, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are hydroxy, halo, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, trifluoromethyl, nitro, cyano, carbalkoxy of 2 to 7 carbon atoms, carboxamido, amino, alkylamino of 1 to 6 carbon atoms or dialkylamino of 2 to 12 carbon atoms;
- R.sup.6 is phenyl, benzyl, 2-, 3-, or 4-pyridinyl, 2-pyrimidinyl or 2-pyrazinyl; any of which may be substituted by one or more hydroxy, halo, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, trifluoromethyl, nitro, cyano, carbalkoxy of 2 to 7 carbon atoms, carboxamido, amino, alkylamino of 1 to 6 carbon atoms or dialkylamino of 2 to 12 carbon atoms;
- and
- n is one of the integers 0, 1, 2, 3, 4 or 5; or a pharmaceutically acceptable salt thereof, with the proviso that when X is --CON(R.sup.7)-- and R.sup.7 is alkyl, R.sup.6 is other than 2-pyrimidinyl.
- 8. A compound of claim 7 in which R.sup.2 and R.sup.3, taken together, are tetramethylene, pentamethylene or hexamethylene.
- 9. A compound of claim 8 in which R.sup.4 is hydrogen and R.sup.5 is alkyl of 1 to 6 carbon atoms, phenyl or benzyl.
- 10. A compound of claim 8 in which R.sup.6 is 2-methoxyphenyl, 2-chlorophenyl or 2-pyrimidinyl.
- 11. The compound of claim 1 which is N-(1,1-dimethylethyl)-N.sup.1 -[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]urea, or a pharmaceutically acceptable salt thereof.
- 12. The compound of claim 1 which is N-[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]-2,2-dimethylpropanamide, or a pharmaceutically acceptable salt thereof.
- 13. The compound of claim 1 which is 2,2-dimethylpropanoic acid 2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl ester, or a pharmaceutically acceptable salt thereof.
- 14. The compound of claim 1 which is 2,2-dimethylpropanoic acid 3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl ester, or a pharmaceutically acceptable salt thereof.
- 15. The compound of claim 1 which is 2,2-dimethylpropanoic acid 3-[4-(2-chlorophenyl)-1-piperazinyl]propyl ester, or a pharmaceutically acceptable salt thereof.
- 16. The compound of claim 6 which is 2,2-dimethylpropanoic acid 3-[4-(2-pyrimidinyl)-1-piperazinyl]propyl ester, or a pharmaceutically acceptable salt thereof.
- 17. The compound of claim 1 which is (R)-N-[1-methyl-2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]trimethylacetamide, or a pharmaceutically acceptable salt thereof.
- 18. The compound of claim 1 which is N-2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl 2,2-dimethylpropanamide dihydrochloride, or a pharmaceutically acceptable salt thereof.
- 19. The compound of claim 1 which is N-(1,1-dimethylethyl)-4-(2-methoxyphenyl)-1-piperazineacetamide, or a pharmaceutically acceptable salt thereof.
- 20. The compound of claim 1 which is N-(1,1-dimethylethyl)-4-(2-pyrimidinyl)-1-piperazinepropanamide, or a pharmaceutically acceptable salt thereof.
- 21. The compound of claim 1 which is 2,2-dimethylpropanoic acid 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl ester, or a pharmaceutically acceptable salt thereof.
- 22. The compound of claim 1 which is tertiary-butyl 3-[1-[4-(2-methoxyphenyl)piperazinyl]]-2-phenylpropanoate, or a pharmaceutically acceptable salt thereof.
- 23. The compound of claim 1 which is N-tertiary-butyl 3-[4-(2-methoxyphenyl)piperazinyl]-2-phenylpropanamide, or a pharmaceutically acceptable salt thereof.
- 24. The compound of claim 1 which is N-tertiary-butyl 2-[[4-(2-methoxyphenyl)piperazinyl]methyl]-3-phenylpropanamide or a pharmaceutically acceptable salt thereof.
- 25. The compound of claim 1 which is N-[2-[4-(2-methoxyphenyl)-1-piperazinyl)ethyl]-1-methylcyclohexanecarboxamide, or a pharmaceutically acceptable salt thereof.
- 26. The compound of claim 7 which is 4-(2-methoxyphenyl)-N-(1-methylcyclohexyl)-1-piperazinepropanamide, or a pharmaceutically acceptable salt thereof.
- 27. The compound of claim 7 which is 4-(2-pyrimidinyl)-N-(1-methylcyclohexyl)-1-piperazinepropanamide, or a pharmaceutically acceptable salt thereof.
- 28. The compound of claim 7 which is N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N'-(1-methylcyclohexyl)urea, or a pharmaceutically acceptable salt thereof.
- 29. The compound of claim 7 which is N-2-(4-(2-pyrimidinyl)-1-piperazinyl)ethyl-1-methylcyclohexylcarboxamide, or a pharmaceutically acceptable salt thereof.
- 30. The compound of claim 7 which is (R)-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-1-methylethyl]-1-methylcyclohexane carboxamide, or a pharmaceutically acceptable salt thereof.
- 31. The compound of claim 7 which is (R)-1-methyl-N-[1-methyl-2-[4-(2-pyrimidinyl)]-1-piperazinyl]ethyl]cyclohexane carboxamide, or a pharmaceutically acceptable salt thereof.
- 32. The compound of claim 1 which is N-(1,1-dimethylethyl)-4-(2-methoxyphenyl)-1-piperazinyl-propanamide, or a pharmaceutically acceptable salt thereof.
- 33. The compound of claim 1 which is 2,2-dimethylpropanoic acid 2-(4-(2-methoxyphenyl)piperazin-1-yl)-1-phenylethyl ester, or a pharmaceutically acceptable salt thereof.
- 34. The compound of claim 1 which is O-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-N-(2-methyl-2-propyl)carbamate, or a pharmaceutically acceptable salt thereof.
- 35. The compound of claim 1 which is N-tert-butyl-2-methoxyphenyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)propanamide, or a pharmaceutically acceptable salt thereof.
- 36. The compound of claim 1 which is N-tert-butyl-3-[1-[4-(2-methoxy)phenyl]piperazinyl]-2-phenyl-propionhydrazide, or a pharmaceutically acceptable salt thereof.
- 37. The compound of claim 1 which is O-tert-butyl-3-[1-(4-(2-methoxy)phenyl)piperazinyl)-2-phenyl-propionohydroxamate, or a pharmaceutically acceptable salt thereof.
Priority Claims (1)
Number |
Date |
Country |
Kind |
8909209 |
Apr 1989 |
GBX |
|
RELATED APPLICATIONS
U.S. patent application Nos. 335,075; 297,509 and 294,853 disclose adamantyl and noradamantyl piperazine amides, carbamates, carbonates and ureas with high 5HT.sub.1A affinitives. These compounds, as well as those disclosed in U.S. Pat. No. 4,797,489 by Abou-Gharbia et al. are useful for treatment of CNS disorders.
US Referenced Citations (7)
Foreign Referenced Citations (5)
Number |
Date |
Country |
814287 |
Oct 1974 |
BEX |
0048045 |
Mar 1982 |
EPX |
0318933 |
Jun 1989 |
EPX |
2432516 |
Feb 1980 |
FRX |
81167 |
May 1985 |
JPX |
Non-Patent Literature Citations (4)
Entry |
Depoortere, Chem. Abst. 93-186411b (1980). |
Synthelabo S. A. Chem. Abst. 93-26461w (1980). |
Najer et al., Chem. Abst. 93-150280a (1980). |
Haeck et al., Chem. Abst. 97-38956g (1982). |