US2023278964A1PendingUtilityA1

2,4-diaminoquinazoline derivatives and medical uses thereof

71
Assignee: JANSSEN SCIENCES IRELAND UNLIMITED COPriority: Mar 1, 2018Filed: Jan 24, 2023Published: Sep 7, 2023
Est. expiryMar 1, 2038(~11.6 yrs left)· nominal 20-yr term from priority
C07D 239/95A61K 31/517A61P 1/16A61P 31/12A61P 35/00A61P 37/06C07D 413/04
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Claims

Abstract

This application relates to quinazoline derivatives, processes for their preparation, pharmaceutical compositions, and medical uses thereof.

Claims

exact text as granted — not AI-modified
1 - 15 . (canceled) 
     
     
         16 . A method of agonizing TLR-8 receptors in a subject suffering from a viral infection, comprising administering an effective amount of compound of formula (I) to the subject in need thereof, wherein formula (I) is represented by: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or solvate thereof, wherein 
         R 1  is of formula (II): 
       
       
         
           
           
               
               
           
         
          wherein n is 0, 1, or 2; 
         or of formula (III): 
       
       
         
           
           
               
               
           
         
          wherein n is 0, 1, or 2, 
         the carbon of R 1  bonded to the amine in the 4-position of the quinazoline is in (R)-configuration, 
         R 2  is hydrogen, deuterium, fluorine, chlorine, methyl, methoxy, cyclopropyl, trifluoromethyl, or carboxylic amide, wherein each of methyl, methoxy and cyclopropyl is optionally substituted by one or more substituents independently selected from fluorine and nitrile, 
         R 3  is hydrogen or deuterium, 
         R 4  is hydrogen, deuterium, fluorine, methyl, carboxylic ester, carboxylic amide, nitrile, cyclopropyl, C 4-7 heterocycle, or 5-membered heteroaryl group, wherein each of methyl, cyclopropyl, C 4-7 heterocycle and 5-membered heteroaryl group is optionally substituted by one or more substituents independently selected from fluorine, hydroxyl, or methyl, 
         and 
         R 5  is hydrogen, deuterium, fluorine, chlorine, methyl, or methoxy, 
         provided that at least one of R 2 , R 3 , R 4  and R 5  is not hydrogen. 
       
     
     
         17 . The method of  claim 16 , wherein R 1  is formula (II): 
       
         
           
           
               
               
           
         
         wherein n is 0, 1, or 2. 
       
     
     
         18 . The method of  claim 17 , wherein n is 1. 
     
     
         19 . The method of  claim 17 , wherein R 2  is fluorine, chlorine or methyl, and wherein methyl is optionally substituted by one or more substituents independently selected from fluorine and nitrile. 
     
     
         20 . The method of  claim 17 , wherein R 2  is fluorine or chlorine. 
     
     
         21 . The method of  claim 17 , wherein R 4  is fluorine or methyl, and wherein methyl is optionally substituted by one or more substituents independently selected from fluorine, hydroxyl, or methyl. 
     
     
         22 . The method of  claim 17 , wherein R 4  is fluorine. 
     
     
         23 . The method of  claim 17 , wherein R 4  is hydrogen. 
     
     
         24 . The method of  claim 17 , wherein R 3  and R 5  are hydrogen 
     
     
         25 . The method of  claim 16 , wherein the compound of formula (I) is chosen from among compounds 1-34: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Compound 
                     
                 
                     
                   number 
                 
                     
                     
                 
                     
                 
                 
                 
                 
               
                     
                   1 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   2 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   3 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   4 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   5 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   6 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   7 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   8 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   9 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   10 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   11 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   12 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   13 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   14 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   15 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   16 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   17 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   18 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   19 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   20 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   21 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   22 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   23 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   24 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   25 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   26 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   27 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   28 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   29 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   30 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   31 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   32 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   33 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
                     
                   34 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                     
                 
             
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         or a pharmaceutically acceptable salt or solvate thereof. 
       
     
     
         26 . The method of  claim 25 , which is chosen from among compounds 1, 2, 3, 4, 5, 7, 9, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 22, 23, 24 and 26 or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         27 . The method of  claim 25 , which is chosen from among compounds 2, 13, 14, 15, 16, 21 and 23 or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         28 . The method of  claim 25 , wherein the compound is 2, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         29 . The method of  claim 25 , wherein the compound is 13, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         30 . The method of  claim 25 , wherein the compound is 14, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         31 . The method of  claim 25 , wherein the compound is 15, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         32 . The method of  claim 25 , wherein the compound is 16, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         33 . The method of  claim 25 , wherein the compound is 21, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         34 . The method of  claim 25 , wherein the compound is 23, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         35 . The method of  claim 16 , wherein the effective amount is an amount that is sufficient to stimulate or activate at least one of activity of TLR8 receptor and activate cytokine production (or secretion).

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