Substituted isoquinolines and methods of using same

Abstract

Novel substituted isoquinoline compounds are disclosed together with novel 2-phenylethylamides useful as precursors or intermediates for the production of the isoquinolines. The substituted isoquinolines exhibit activity in antagonizing the effects of platelet activating factor (PAF).

What is claimed as new and desired to be protected by Letters Patent is set forth in the appended claims. 
     
       1. A compound having the formula: ##STR8## wherein ##STR9## ##STR10## R 4  =H, --OCH 3 , Halogen n=0-5 X=H, --OCH 3 , Halogen   Y=H, --OCH 3 , Halogen   C 3  -C 4  bond=saturated & unsaturated, wherein at least one of R 2 , R 3 , R 4 , X and Y is other than hydrogen .Iadd., and wherein when R 1 , R 2 , R 4 , X and Y=H, the C 3  -C 4  bond is saturated, and n=0 , then R 3  is other than H or CH 3 . .Iaddend.     
     
     
       2. A compound according to claim 1 wherein R 1  and R 3  are H. 
     
     
       3. A compound according to claim 1 wherein R 1  is --OH. 
     
     
       4. A compound according to claim 1 wherein R 2  is H or --CH 3 . 
     
     
       5. A compound according to claim 1 wherein R 4  is H or --OCH 3 . 
     
     
       6. A compound according to claim 1 wherein m=1 and Z is ##STR11## 
     
     
       7. A compound according to claim 1 wherein n=0-2. 
     
     
       8. A compound according to claim 1 wherein the C 3  -C 4  bond is unsaturated. 
     
     
       9. A compound according to claim 1 wherein the C 3  -C 4  bond is saturated. 
     
     
       10. A pharmaceutical composition comprising a compound according to claim 1 in a pharmaceutical dosage form. 
     
     
       11. A composition according to claim 10 wherein said dosage form is an oral dosage form selected from the group consisting of capsules, tablets, caplets, lozenges, liquids, elixirs and suspensions. 
     
     
       12. A composition according to claim 10 wherein said dosage form is a parenteral dosage form selected from the group consisting of injectable propylene glycol solutions and isotonic saline solutions. 
     
     
       13. A composition according to claim 10 wherein the compound of claim 1 is present in an amount effective to antagonize a PAF-mediated response in a human or animal patient. 
     
     
       14. A method of providing antagonism to a PAF-mediated response in a human or animal patient requiring such treatment comprising the administration to the patient of a pharmaceutical composition according to claim 10 from one to four times daily. 
     
     
       15. A method according to claim 14 wherein said pharmaceutical composition is administered orally. 
     
     
       16. A method according to claim 14 wherein said pharmaceutical composition is administered parenterally. 
     
     
       17. A method according to claim 14 wherein the patient requires treatment for an indication selected from the group consisting of asthma, inflammatory and allergic disorders, septic shock, transplant rejection and renal disease.