Method of using diketopiperazines and composition containing them

Abstract

The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R 1 and R 2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.

1 - 28 . (canceled) 
     
     
         29 . A method for treating a disease or condition selected from the group consisting of an allergy, arthritis, an autoimmune disease, ophthalmic inflammation, pain and psoriasis, the method comprising administering to an animal in need thereof an effective amount of a compound having the formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is —CH 2 COR 3 , or —CH 2 CH 2 COR 3 ; 
 R 2  is the side chain of an amino acid selected from the group consisting of alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, tyrosine and norvaline; 
 R 3  is —OH, —NH 2 , —OR 4 , —NHR 4 , or —NR 4 R 4 ; and 
 each R 4  is independently an alkyl, aryl, alkylaryl, or arylalkyl, or 
 a physiologically-acceptable salt thereof. 
 
     
     
         30 . The method of  claim 29  wherein the disease or condition is an allergy. 
     
     
         31 . The method of  claim 29  wherein the disease or condition is arthritis. 
     
     
         32 . The method of  claim 29  wherein the disease or condition is an autoimmune disease. 
     
     
         33 . The method of  claim 29  wherein the disease or condition is ophthalmic inflammation. 
     
     
         34 . The method of  claim 29  wherein the disease or condition is pain. 
     
     
         35 . The method of  claim 29  wherein the disease or condition is psoriasis. 
     
     
         36 . The method of  claim 29  wherein R 2  is the side chain of alanine, valine, leucine, isoleucine or norvaline. 
     
     
         37 . The method of  claim 36  wherein R 2  is the side chain of alanine. 
     
     
         38 . The method of  claim 29  wherein R 3  is —OH and R 1  is —CH 2 COOH. 
     
     
         39 . The method of  claim 36  wherein R 3  is —OH and R 1  is —CH 2 COOH. 
     
     
         40 . The method of  claim 37  wherein R 3  is —OH and R 1  is —CH 2 COOH. 
     
     
         41 . The method of  claim 29  wherein R 3  is —NH 2  and R 1  is —CH 2 CONH 2 . 
     
     
         42 . The method of  claim 36  wherein R 3  is —NH 2  and R 1  is —CH 2 CONH 2 . 
     
     
         43 . The method of  claim 37  wherein R 3  is —NH 2  and R 1  is —CH 2 CONH 2 . 
     
     
         44 . The method of  claim 29  wherein R 2  is the side chain of serine, threonine or tyrosine. 
     
     
         45 . The method of  claim 44  wherein R 2  is the side chain of tyrosine. 
     
     
         46 . The method of  claim 44  wherein R 3  is —OH and R 1  is —CH 2 CH 2 COOH. 
     
     
         46 . The method of  claim 45  wherein R 3  is —OH and R 1  is —CH 2 CH 2 COOH. 
     
     
         47 . The method of  claim 44  wherein R 3  is —NH 2  and R 1  is —CH 2 CH 2 CONH 2 . 
     
     
         47 . The method of  claim 44  wherein R 3  is —NH 2  and R 1  is —CH 2 CH 2 CONH 2 . 
     
     
         48 . The method of  claim 29  wherein R 2  is the side chain of aspartic acid, asparagine, glutamic acid or glutamine.