5-Amino or substituted amino-7-phenyl or substituted phenyl-2,3-dihydro-1H-1,4-diazepines

Abstract

Compounds of the formula ##STR1## wherein R 1 is hydrogen, alkyl of 1 to 6 carbon atoms or amino, R 2 is hydrogen or alkyl of 1 to 6 carbon atoms, with the provisos that (1) at least one of R 1 and R 2 is not a tertiary alkyl group and (2) R 2 is hydrogen when R 1 is amino, or R 1 and R 2 taken together and with the nitrogen atom to which they are joined are pyrrolidino, piperidino or N'-2-hydroxyethylpiperazino, each X' is independently alkyl or 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halo, or two X's on adjacent carbon atoms together are methylenedioxy, and n is 0, 1, 2 or 3, and the pharmaceutically acceptable acid addition salts thereof, are useful as anti-obesity and anti-diabetic agents. The compounds wherein R 1 is alkyl and R 2 is hydrogen are synthesized by a two-step synthesis from 2-alkyl-5-arylisoxazolium salts and ethylenediamine. The compounds wherein R 1 and R 2 are hydrogen are synthesized by cleaving the t-butyl group from the corresponding compounds wherein R 1 is t-butyl and R 2 is hydrogen. The compounds wherein R 1 is amino are synthesized from the corresponding compounds wherein R 1 is hydrogen or alkyl. All of the compounds are synthesized by reacting ammonia, a suitable amine or hydrazine with a compound of the formula ##STR2## wherein R' is primary or secondary alkyl of 1 to 4 carbon atoms.

What is claimed is: 
     
       1. A compound of the formula ##STR43## wherein R 1  is hydrogen, alkyl of 1 to 6 carbon atoms or amino, R 2  is hydrogen or alkyl of 1 to 6 carbon atoms, with the provisos that (1) at least one of R 1  and R 2  is not a tertiary alkyl group and (2) R 2  is hydrogen when R 1  is amino, each X' is independently alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halo, or two X's on adjacent carbon atoms together are methylenedioxy, and   n is 0, 1, 2 or 3, or a pharmaceutically acceptable acid addition salt thereof.     
     
     
       2. A pharmaceutically acceptable acid addition salt of a compound according to claim 1. 
     
     
       3. A compound according to claim 1 having the formula ##STR44## wherein R is alkyl of 1 to 6 carbon atoms, each X is independently alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halo, and m is 0, 1 or 2, or a pharmaceutically acceptable acid addition salt thereof.     
     
     
       4. A compound according to claim 3 having the formula ##STR45## wherein R is alkyl of 1 to 6 carbon atoms, and each Y is hydrogen, alkyl of 1 to 3 carbon atoms, methoxy, ethoxy, chloro or bromo, with the proviso that at least one Y is hydrogen, or a pharmaceutically acceptable acid addition salt thereof.     
     
     
       5. A compound according to claim 4 wherein each Y is hydrogen,   or a pharmaceutically acceptable acid addition salt thereof.   
     
     
       6. A compound according to claim 1 wherein each X' is independently alkyl of 1 to 3 carbon atoms, methoxy, ethoxy, chloro or bromo, and   n is 0, 1 or 2, or a pharmaceutically acceptable acid addition salt thereof.     
     
     
       7. A compound according to claim 6 having the formula ##STR46## wherein R 1  is hydrogen, alkyl of 1 to 6 carbon atoms or amino, and each Y' is independently hydrogen, methyl, ethyl, methoxy or ethoxy, or a pharmaceutically acceptable acid addition salt thereof.   
     
     
       8. A compound according to claim 7 wherein each Y' is independently hydrogen, methyl or methoxy,   or a pharmaceutically acceptable acid addition salt thereof.   
     
     
       9. A compound according to claim 7 wherein R 1  is hydrogen or t-butyl,   or a pharmaceutically acceptable acid addition salt thereof.   
     
     
       10. A compound according to claim 9 wherein each Y' is independently hydrogen, methyl or methoxy,   or a pharmaceutically acceptable acid addition salt thereof.   
     
     
       11. A compound according to claim 10 having the formula ##STR47## wherein R 1  ' is hydrogen or t-butyl, Y 1  is hydrogen, methyl or methoxy, and Y 2  is hydrogen or methyl, or a pharmaceutically acceptable acid addition salt thereof.     
     
     
       12. A pharmaceutically acceptable acid addition salt of a compound according to claim 11. 
     
     
       13. A compound according to claim 11 wherein R 1  ' is hydrogen,   or a pharmaceutically acceptable acid addition salt thereof.   
     
     
       14. A pharmaceutically acceptable acid addition salt of a compound according to claim 13. 
     
     
       15. The compound according to claim 13 having the formula ##STR48## or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       16. The compound according to claim 15 having the formula ##STR49## 
     
     
       17. A pharmaceutical acceptable acid addition salt according to claim 15 of the compound of the formula ##STR50## 
     
     
       18. The pharmaceutically acceptable acid addition salt according to claim 17 having the formula ##STR51## 
     
     
       19. The compound according to claim 11 having the formula ##STR52## or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       20. The pharmaceutically acceptable acid addition salt according to claim 19 having the formula ##STR53## 
     
     
       21. The compound according to claim 11 having the formula ##STR54## or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       22. The compound according to claim 21 having the formula ##STR55## 
     
     
       23. A pharmaceutically acceptable acid addition salt according to claim 21 of the compound of the formula ##STR56## 
     
     
       24. The pharmaceutically acceptable acid addition salt according to claim 23 having the formula ##STR57## 
     
     
       25. The pharmaceutically acceptable acid addition salt according to claim 23 having the formula ##STR58## 
     
     
       26. The compound according to claim 11 having the formula ##STR59## or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       27. The pharmaceutically acceptable acid addition salt according to claim 26 having the formula ##STR60## 
     
     
       28. The compound according to claim 11 having the formula ##STR61## or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       29. The pharmaceutically acceptable acid addition salt according to claim 28 having the formula ##STR62## 
     
     
       30. The compound according to claim 11 having the formula ##STR63## or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       31. The pharmaceutically acceptable acid addition salt according to claim 30 having the formula ##STR64## 
     
     
       32. The compound according to claim 8 having the formula ##STR65## or a pharmaceutically acceptable acid addition salt thereof.