Imidazo[1,5-d]-as-triazine-4(3H)-ones and thiones

Abstract

There is provided substituted imidazo[1,5-d]-as-triazine-4(3H)-ones and substituted imidazo[1,5-d]-as-triazin-4(3H)-thiones useful as inhibitors of the enzyme cyclic-AMP phosphodiesterase and as broad spectrum herbicides.

We claim: 
     
       1. A compound of the formula: ##STR52## wherein X is divalent oxygen or divalent sulfur; R 1  is selected from the group consisting of hydrogen, alkyl (C 1  -C 3 ), chloro, bromo, iodo and haloalkyl (C 1  -C 3 ); R 2  is selected from the group consisting of hydrogen, alkyl .[.(C 1  -C 4 ).]..Iadd.(C 1  -C 4 ).Iaddend., cycloalkyl (C 3  -C 6 ), methoxymethyl, benzyl, naphthyl, phenyl and mono-substituted phenyl wherein said substituent is selected from the group consisting of .[.halo, alkyl (C 1  -C 4 ), haloalkyl (C 1  -C 3 ) amino, dialkyl-.]..Iadd.halogen, alkyl (C 1  -C 4 ), alkoxy (C 1  -C 4 ), haloalkyl (C 1  -C 3 ), amino, dialkyl-.Iaddend.amino and nitro; R 3  is selected from the group consisting of hydrogen, alkyl (C 1  -C 3 ), alkenyl (C 3  -C 4 ) and alkynyl (C 3  -C 4 ); R 4  is selected from the group consisting of hydrogen and alkyl (C 1  -C 3 ). 
     
     
       2. The compound according to claim 1 wherein X is oxygen; R 1  is methyl, bromo or chloro; R 2  is cycloalkyl (C 3  -C 6 ), phenyl or m-tolyl; and R 3  and R 4  are both hydrogen. 
     
     
       3. The compound according to claim 1 wherein X is oxygen and R 1  and R 2  are both hydrogen. 
     
     
       4. The compound according to claim 1 wherein X is sulfur and R 1  and R 2  are both hydrogen. 
     
     
       5. The compound according to claim 1 wherein X is oxygen, R 1  is methyl, and R 2  is phenyl. 
     
     
       6. The compound according to claim 1 wherein X is sulfur, R 1  is methyl, and R 2  is phenyl. 
     
     
       7. The compound according to claim 1 wherein X is oxygen and R 1  and R 2  are both methyl. 
     
     
       8. The compound according to claim 1 wherein X is sulfur and R 1  and R 2  are both methyl. 
     
     
       9. The compound according to claim 1 wherein X is oxygen, R 1  is bromo, and R 2  is phenyl. 
     
     
       10. The compound according to claim 1 wherein X is sulfur, R 1  is methyl, and R 2  is benzyl. 
     
     
       11. The compound according to claim 1 wherein X is oxygen, R 1  is chloro and R 2  is phenyl. 
     
     
       12. The compound according to claim 1 wherein X is oxygen, R 1  and is R 3  are both methyl, and R 2  is phenyl. 
     
     
       13. The compound according to claim 1 wherein X is oxygen, R 1  is methyl and R 2  is n-propyl. 
     
     
       14. The compound according to claim 1 wherein X is oxygen, R 1  is methyl, and R 2  is tert-butyl. 
     
     
       15. The compound according to claim 1 wherein X is oxygen, R 1  is chloro, and R 2  is p-chlorophenyl. 
     
     
       16. The compound according to claim 1 wherein X is oxygen, R 1  is methyl, and R 2  is cyclohexyl. 
     
     
       17. The compound according to claim 1 wherein X is oxygen, R 1  is methyl, and R 2  is m-tolyl. 
     
     
       18. The compound according to claim 1 wherein X is oxygen, R 1  is iodo, and R 2  is phenyl. 
     
     
       19. The compound according to claim 1 wherein X is oxygen, R 1  is methyl and R 2  is p-aminophenyl. 
     
     
       20. The compound according to claim 1 wherein X is oxygen, R 1  is bromo, and R 2  is m-dimethylaminophenyl. 
     
     
       21. The compound according to claim 1 wherein R 1  is methyl and R 2  is 2-naphthyl. 
     
     
       22. A method of inhibiting the enzyme phosphodiesterase in a mammal which comprises administering internally to said mammal an effective amount of a compound of the formula: ##STR53## wherein X is divalent oxygen or divalent sulfur; R 1  is selected from the group consisting of hydrogen, chloro, bromo and alkyl having up to 3 carbon atoms; and R 2  is selected from the group consisting of hydrogen, alkyl having up to 4 carbon atoms, phenyl, benzyl, methoxymethyl and o-propoxyphenyl. 
     
     
       23. A therapeutic composition in dosage unit form useful for inhibiting the enzyme phosphodisterase in mammals comprising from about 1.0 mg. to about 25.0 mg. per kg. of body weight per daily dosage unit, in association with a pharmaceutical carrier, of a compound of that formula: ##STR54## wherein X is divalent oxygen or devalent sulfur; R 1  is selected from the group consisting of hydrogen, chloro, bromo and alkyl having up to 3 carbon atoms, and R 2  is selected from the group consisting of hydrogen, alkyl having up to 4 carbon atoms, phenyl, benzyl, methoxymethyl and o-propoxyphenyl. 
     
     
       24. The process of preparing compounds of the formula: ##STR55## wherein R 1  is hydrogen or alkyl having up to 3 carbon atoms and R 2  is hydrogen, alkyl having up to 4 carbon atoms, phenyl, benzyl, methoxymethyl or o-propoxyphenyl which comprises heating a compound of the formula: ##STR56## wherein R is methyl or ethyl and R 1  and R 2  are as hereinabove defined in a non-polar high boiling organic solvent at a temperature of 175°-275° C. for a period of time sufficient for a substantial degree of ring closure to occur. 
     
     
       25. The process of preparing compounds of the formula: ##STR57## wherein R 1  is hydrogen or alkyl having up to 3 carbon atoms and R 2  is hydrogen, alkyl having up to 4 carbon atoms, phenyl, benzyl, methoxymethyl or o-propoxyphenyl which comprises heating a compound of the formula: ##STR58## wherein R is methyl or ethyl and R 1  and R 2  are as hereinabove defined in a non-polar high boiling organic solvent at a temperature of 175°-275° C. for a period of time sufficient for a substantial degree of ring closure to occur. 
     
     
       26. The process of preparing compounds of the formula: ##STR59## wherein X is divalent oxygen or divalent sulfur; R 1  is chloro or bromo; and R 2  is hydrogen, alkyl having up to 4 carbon atoms, phenyl, benzyl, methoxymethyl or o-propoxyphenyl which comprises treating a compound of the formula: ##STR60## wherein X and R 2  are as hereinabove defined with chlorine or bromine in an inert solvent at a temperature of 60°-90° C. for a period of time sufficient for a substantial degree of halogenation to occur. 
     
     
       27. The process of preparing compounds of the formula: ##STR61## wherein R 1  is hydrogen, chloro, bromo or alkyl having up to 3 carbon atoms and R 2  is hydrogen, alkyl having up to 4 carbon atoms, phenyl, benzyl, methoxymethyl or o-propoxyphenyl which comprises treating a compound of the formula: ##STR62## wherein R 1  and R 2  are as hereinabove defined with phosphorus pentasulfide in an inert solvent at a temperature of 100°-150° C. for a period of time sufficient for a substantial degree of replacement to occur. .Iadd. 
     
     
       28.  The compound according to claim 1 wherein X is sulfur; R 2  is n-propyl; and R 1 , R 3  and R 4  are all hydrogen. .Iaddend..Iadd. 29. The compound according to claim 1 wherein X is sulfur; R 1  is methyl; R 2  is n-propyl; and R 3  and R 4  are both hydrogen. .Iaddend..Iadd. 30. The compound according to claim 1 wherein X is sulfur; R 2  is methyl; and R 1 , R 3  and R 4  are all hydrogen. .Iaddend..Iadd. 31. The compound according to claim 1 wherein X is oxygen; R 1  is methyl; R 2  is phenyl; and R 3  and R 4  are both hydrogen. .Iaddend..Iadd. 32. The compound according to claim 1 wherein X is oxygen; R 2  is n-propyl; and R 1 , R 3  and R 4  are all hydrogen. .Iaddend..Iadd. 33. The compound according to claim 1 wherein X is oxygen; R 1  and R 2  are both methyl; and R 3  and R 4  are both hydrogen. .Iaddend..Iadd. 34. The compound according to claim 1 wherein X is oxygen, R 1  is methyl; and R 2 , R 3  and R 4  are all hydrogen. .Iaddend..Iadd. 35. The compound according to claim 1 wherein X is oxygen; R 1  is methyl; R 2  is tert-butyl; and R 3  and R 4  are both hydrogen. .Iaddend. .Iadd. 36. The compound according to claim 1 wherein X is oxygen; R 1  is methyl; R 2  is n-propyl; and R 3  and R 4  are both hydrogen. .Iaddend..Iadd. 37. The compound according to claim 1 wherein X is oxygen; R 1  is methyl; R 2  is p-chlorophenyl; and R 3  and R 4  are both hydrogen. .Iaddend..Iadd. 38. The compound according to claim 1 wherein X is oxygen; R 1  is methyl; R 2  is n-butyl; and R 3  and R 4  are both hydrogen. .Iaddend..Iadd. 39. The compound according to claim 1 wherein X is oxygen; R 1  is methyl; R 2  is cyclopropyl; and R 3  and R 4  are both hydrogen. .Iaddend..Iadd. 40. The compound according to claim 1 wherein X is oxygen; R 1  is bromo; R 2  is m-anilino; and R 3  and R 4  are both hydrogen. .Iaddend..Iadd. 41. The compound according to claim 1 wherein X is oxygen; R 2  is m-nitrophenyl; and R 1 , R 3  and R 4  are all hydrogen. .Iaddend..Iadd. 42. The compound according to claim 1 wherein X is oxygen; R 1  and R 2  are both bromo; and R 3  and R 4  are both hydrogen. .Iaddend..Iadd. 43. The compound according to claim 1 wherein X is oxygen; R 1  and R 3  are both methyl; R 2  is phenyl; and R 4  is hydrogen. .Iaddend..Iadd. 44. The compound according to claim 1 wherein X is oxygen; R 1  is methyl; R 2  is phenyl; R 3  is allyl; and R 4  is hydrogen. .Iaddend..Iadd. 45. The compound according to claim 1 wherein X is oxygen; R 1  is methyl; R 2  is phenyl; R 3  is propargyl; and R 4  is hydrogen. .Iaddend..Iadd. 46. The compound according to claim 1 wherein X is oxygen; R 1  is methyl; R 2  is phenyl; R 3  is n-propyl; and R 4  is hydrogen. .Iaddend. .Iadd. 47. The compound according to claim 1 wherein X is oxygen; R 1  is methyl; R 2  is phenyl; R 3  is benzyl; and R 4  is hydrogen. .Iaddend..Iadd. 48. A compound of the formula: ##STR63## wherein X is divalent oxygen or divalent sulfur; R 1  is hydrogen, alkyl having from 1 to 3 carbon atoms or bromo; R 2  is selected from the group consisting of hydrogen, alkyl having from 1 to 4 carbon atoms, cycloalkyl having from 3 to 6 carbon atoms, bromo, phenyl, p-chlorophenyl, m-nitrophenyl and m-aminophenyl; and R 3  is hydrogen, alkyl having 
     
     
        from 1 to 3 carbon atoms, allyl or propargyl. .Iaddend..Iadd. 49.  The method of meliorating asthma in a mammal which comprises administering internally to said mammal an anti-asthmatic effective amount of a compound of claim 48. .Iaddend..Iadd. 50. A compound of the formula: ##STR64## wherein X is divalent oxygen or divalent sulfur; R 1  is hydrogen or alkyl having up to 3 carbon atoms; R 2  is hydrogen or alkyl having up to 4 carbon atoms; and R 3  is hydrogen or allyl having up to 3 carbon 
     
     
        atoms. .Iaddend..Iadd. 51.  The method of meliorating asthma in a mammal which comprises administering internally to said mammal an anti-asthmatic effective amount of a compound of claim 50. .Iaddend.