Claims
- 1. A Compound of Formula I ##STR16## and the pharmaceutically acceptable acid addition salt or hydrate thereof wherein
- R.sup.1 and R.sup.2 are independently selected from hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen and trifluoromethyl;
- R.sup.3 is hydrogen, halogen, C.sub.1-4 alkoxy, nitro or --NR.sup.9 R.sup.10 with R.sup.9 and R.sup.10 being independently selected from hydrogen or C.sub.1-4 alkyl, alkanoyl and ##STR17## R.sup.4 is hydrogen or C.sub.1-4 alkyl; R.sup.5 and R.sup.6 are independently selected from hydrogen, --CONR.sup.6 R.sup.10, oxo and --CO.sub.2 R.sup.11 with R.sup.11 being C.sub.1-4 alkyl, or R.sup.5 and R.sup.6 can be taken together to form a methylene or ethylene bridge;
- R.sup.7 and R.sup.8 taken together is a butylene or are both ##STR18## with R.sup.12 being hydrogen, halogen, trifluoromethyl, C.sub.1-4 alkyl or C.sub.2-4 alkyl-N(R.sup.4).sub.2 ;
- n is zero or an integer from 1 to 4; and
- X is S, O, or NH.
- 2. A compound of claim 1 wherein X is S.
- 3.
- A compound of claim 1 wherein X is O.
- 4. A compound of claim 1 wherein X is NH.
- 5. A compound of claim 1 wherein R.sup.1 and R.sup.2 are selected from methyl and chloro.
- 6. A compound of claim 1 wherein n is 1.
- 7. A compound of claim 1 wherein R.sup.7 and R.sup.8 are phenyl.
- 8. A compound of claim 1 selected from the group consisting of N-(2,6-dimethylphenyl)-4-[(4,5-diphenyl-2-oxazolyl)methyl]-1-piperazineacetamide; N-(2,6-dichlorophenyl)-4-[(4,5-diphenyl-2-oxazolyl)methyl]-1-piperazineacetamide; 4-[[4,5-bis(4-ethylphenyl)-2-oxazolyl]methyl]-N-(2,6-dimethylphenyl)-1-piperazineacetamide; 4-[[4,5-bis(4-fluorophenyl)-2-oxazolyl]methyl]-N-(2,6-dimethylphenyl)-1-piperazineacetamide; 4-[[4,5-bis[4-(trifluoromethyl)-phenyl]-2-oxazolyl]methyl]-N-(2,6-dimethylphenyl)-1-piperazineacetamide; 4-[[4,5-bis(3-chlorophenyl)-2-oxazolyl]methyl]-N-(2,6-dimethylphenyl)-1-piperazineacetamide; 4-[[4,5-diphenyl-2-oxazolyl]ethyl]-N-(2,6-dimethylphenyl)-1-piperazineacetamide; N-(2,6-dimethylphenyl)-4-[4-(4,5-diphenyl-2-oxazolyl)propyl]-1-piperazineacetamide; N-(2,6-dimethylphenyl)-4-[4-(4,5-diphenyl-2-oxazolyl)butyl]-1-piperazineacetamide; N-(4-amino-2,6-dichlorophenyl)-4-[(4,5-diphenyl oxazolyl)methyl]-1-piperazineacetamide; 4-[(4,5-diphenyl-2-oxazolyl)methyl]-N-phenyl-1-piperazineacetamide; N-(4-chlorophenyl)-4-[(4,5-diphenyl-2-oxazolyl)methyl]-1-piperazineacetamide; 4-[(4,5-diphenyl-2-oxazolyl)methyl] -N-(4-fluorophenyl)-1-piperazineacetamide: 4-[(4,5-diphenyl-2-oxazolyl)methyl]-N-(4-methoxylphenyl)-1-piperazineacetamide; 4-[(4,5-diphenyl-2-oxazolyl)methyl]-N-(4-methylphenyl)-1-piperazineacetamide; N-(2,6-dichlorophenyl-4-[(4,5-diphenyl-2-oxazolyl)methyl]-1-piperazineacetamide; 2,6-dimethylphenyl-4-[[4,5-(4-methoxyphenyl)-2-oxazolyl]methyl]-1-piperazineacetamide.
- 9. The compound of claim 8, N-(4-amino-2,6-dichlorophenyl)-4-[(4,5-diphenyl-2-oxazolyl)methyl]-1-piperazineacetamide.
- 10. A compound of claim 1 selected from the group consisting of 4-[[4,5-bis(4-ethylphenyl)-2-imidazolyl]methyl-N-(2,6-dimethylphenyl)-1-piperazineacetamide; N-(2,6-dimethylphenyl)-4-[(4,5-diphenyl-2-imidazolyl)methyl]-1-piperazineacetamide; N-(2,6-dimethylphenyl)-4-[4-(4,5-diphenyl-2-thiazolyl)butanyl]-1-piperazineacetamide; N-(2,6-dimethylphenyl)-4-[(4,5-diphenyl-2-thiazolyl)methyl]-1-piperazineacetamide.
- 11. A compound of claim 1 selected from the group consisting of ethyl-4-[[[(2,6-dimethylphenyl)amino]carboxymethyl]-1-[(4,5-diphenyl-2-oxazolyl)methyl)-2-piperazinecarboxylate; 2-aminocarbonyl-4-[[4,5 diphenyl-2-oxazolyl]methyl]-N-(2,6-dimethylphenyl)-1-piperazineacetamide; (1S, 4S) N-(2,6-dimethylphenyl)-5-[(4,5-diphenyl-2-oxazolyl)methyl]-2,5-diazabicyclo[2,2,1]heptane-2-acetamide; 2-aminocarbonyl N-(2,6-dimethylphenyl)-4-[[4,5-diphenyl-2-oxazolyl)methyl]-1-piperazineacetamide; 3-(aminocarbonyl)-N-(4-amino-2,6-dichlorophenyl)-4-[(4,5-diphenyl(-2-oxazolyl)methyl-1-piperazineacetamide; 2-aminocarbonyl-N-(4-amino-2,6-dichlorophenyl,-4-[(4,5-diphenyloxazolyl)methyl-1-piperazineacetamide.
- 12. The compound of claim 11, 2-aminocarbonyl-4-[(4,5-diphenyl-2-oxalyl)methyl]-N-(4-amino-2,6-dichlorophenyl)-1-piperazineacetamide.
- 13. A process for protecting CNS and cardiac tissue from ischemia which comprises administering an effective ischemia-protective amount of a compound of claim 1 to a mammal susceptible to or suffering from ischemia.
- 14. The process of claim 13 wherein the claim 1 compound is N-(4-amino-2,6-dichlorophenyl)-4-[(4,5-diphenyl-2-oxazolyl)methyl]-1-piperazineacetamide.
- 15. An antiischemic pharmaceutical composition, suitable for systemic administration to a mammal, comprising a pharmaceutical carrier and a compound of claim 1.
- 16. The antiischemic pharmaceutical composition of claim 15 wherein the claim 1 compound is N-(4-amino-2,6-dichlorophenyl)-4-[(4,5-diphenyl-2-oxazolyl)methyl]-1-piperazineacetamide.
CROSS REFERENCE TO RELATED APPLICATION
This is a continuation-in-part application of Ser. No. 08/048,338 filed Apr. 15, 1993 now abandoned, which is itself a continuation-in-part application of Ser. No. 07/923,399 filed Jul. 31, 1992 and now abandoned.
US Referenced Citations (5)
Foreign Referenced Citations (5)
Number |
Date |
Country |
0068544 |
Jan 1983 |
EPX |
0285219 |
Oct 1988 |
EPX |
0388909 |
Sep 1990 |
EPX |
WO9104032 |
Apr 1991 |
EPX |
2459242 |
Jan 1981 |
FRX |
Non-Patent Literature Citations (2)
Entry |
Inoue et al, "2-Aminomethyl-5-phenyloxazoles", Chemical Abstracts, vol. 91 (1979), pp. 707, paragraph: 91:56986x. |
Inoue et al, "2-Aminomethyl-5-phenyloxazoles", Chemical Abstracts, vol. 91 (1979), pp. 707-708, paragraph: 91:56987y. |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
48338 |
Apr 1993 |
|
Parent |
923399 |
Jul 1992 |
|