Substituted tetrahydrocarbazole and carbazole carboxamide compounds

Abstract

R1 is F, Cl, —CN, or —CH3; R2 is Cl or —CH3; R3 is —C(CH3)2OH or —CH2CH2OH; Ra is H or —CH3; each Rb is independently F, Cl, —CH3, and/or —OCH3; and n is zero, 1, or 2. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

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         14 . A compound of Formula (IA): 
       
         
           
           
               
               
           
         
         wherein: 
         Q is: 
       
       
         
           
           
               
               
           
         
         R 1  is F, Cl, —CN, or —CH 3 ; 
         R 2  is Cl or —CH 3 ; 
         R 3  is —C(CH 3 ) 2 OH or —CH 2 CH 2 OH; 
         each R b  is independently F, Cl, —CH 3 , and/or —OCH 3 ; and 
         n is zero, 1, or 2. 
       
     
     
         15 . The compound according to  claim 14  having the structure of Formula (IIIA-1): 
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound according to  claim 14  having the structure of Formula (IIIA-2): 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound according to  claim 14  wherein R 1  is F or Cl. 
     
     
         18 . The compound according to  claim 14  wherein R 2  is —CH 3 . 
     
     
         19 . The compound according to  claim 14  wherein R 3  is —C(CH 3 ) 2 OH. 
     
     
         20 . The compound according to  claim 14  wherein:
 R b  is F or Cl; and 
 n is 1. 
 
     
     
         21 . The compound according to  claim 14  wherein:
 R 1  is F or Cl; 
 R 2  is —CH 3 ; 
 R 3  is —C(CH 3 ) 2 OH; 
 R b  is F or Cl; and 
 n is 1. 
 
     
     
         22 . The compound according to  claim 14  wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         23 . A pharmaceutical composition comprising a compound according to  claim 14  and a pharmaceutically acceptable carrier. 
     
     
         24 . A method for treating a disease comprising the administration to a subject in need thereof a therapeutically-effective amount of at least one compound according to  claim 14 , wherein said disease is selected from systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis (MS), or transplant rejection, wherein treatment is inhibiting, arresting the development, relieving and/or causing regression of the disease. 
     
     
         25 . The method according to  claim 24  wherein said disease is rheumatoid arthritis.