US2018235974A1PendingUtilityA1

Compounds comprising tricyclic heterocyclic compounds

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Assignee: KARUS THERAPEUTICS LTDPriority: Aug 19, 2015Filed: Aug 19, 2016Published: Aug 23, 2018
Est. expiryAug 19, 2035(~9.1 yrs left)· nominal 20-yr term from priority
A61P 35/00A61P 37/02A61P 37/06A61P 35/02A61P 29/00A61P 19/02A61K 9/2054A61K 9/2018A61K 31/5386A61K 9/2027A61K 31/519A61K 31/5377A61K 9/2095
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Claims

Abstract

The invention relates to a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and at least one pharmaceutical excipient selected from the group consisting of fillers, binders, disintegrants, glidants and lubricants, wherein the compound according to formula I is represented by:

Claims

exact text as granted — not AI-modified
1 . A pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and at least one pharmaceutical excipient selected from the group consisting of fillers, binders, disintegrants, glidants and lubricants, wherein the compound according to formula I is represented by: 
       
         
           
           
               
               
           
         
       
       wherein:
 W is O, N—H, N—(C 1 -C 10 alkyl) or S; 
 each X is independently CH or N; 
 R 1  is a 5 to 7-membered saturated or unsaturated, optionally substituted heterocycle containing at least 1 heteroatom selected from N or O; 
 R 2  is LY; 
 each L is a direct bond, C 1 -C 10  alkylene, C 2 -C 10  alkenylene or C 2 -C 10  alkynylene; 
 Y is an optionally substituted fused, bridged or spirocyclic non-aromatic 5-12 membered heterocycle containing up to 4 heteroatoms selected from N or O; and 
 each R 3  is independently H, C 1 -C 10  alkyl, halogen, fluoro C 1 -C 10  alkyl, O— C 1 -C 10  alkyl, NH—C 1 -C 10  alkyl, S—C 1 -C 10  alkyl, O-fluoro C 1 -C 10  alkyl, NH-acyl, NH—C(O)—NH—C 1 -C 10  alkyl, C(O)—NH—C 1 -C 10  alkyl, aryl or heteroaryl. 
 
     
     
         2 . The composition according to  claim 1 , wherein the compound according to formula I is in its succinate salt form. 
     
     
         3 . The composition according to  claim 1 , further comprising a surfactant in an amount of from 0.1 to 5 wt % based on the total weight of the composition. 
     
     
         4 . The composition according to  claim 1 , wherein the composition is in the form of a tablet or capsule. 
     
     
         5 . The composition according to  claim 1 , wherein the composition comprises at least two or at least three pharmaceutical excipients. 
     
     
         6 . The composition according to  claim 1 , wherein the compound according to formula I is present in an amount of from 5 to 30 wt % based on the total weight of the composition. 
     
     
         7 . The composition according to  claim 1 , wherein a filler is present in an amount of from 10 to 90 wt % based on the total weight of the composition. 
     
     
         8 . The composition according to  claim 1 , wherein a binder is present in an amount of from 0.1 to 20 wt % based on the total weight of the composition. 
     
     
         9 . The composition according to  claim 1 , wherein a disintegrant is present in an amount of from 1 to 20 wt % based on the total weight of the composition. 
     
     
         10 . The composition according to  claim 1 , wherein a lubricant is present in an amount of from 0.5 to 5 wt % based on the total weight of the composition. 
     
     
         11 . The composition according to  claim 1 , wherein the composition comprises:
 1 to 50 wt % of a compound according to  claim 1 ;   10 to 90 wt % of at least one filler;   0.1 to 20 wt % of at least one binder;   1 to 20 wt % of at least one disintegrant; and   0.1 to 10 wt % of at least one lubricant or glidant.   
     
     
         12 . The composition according to  claim 1 , wherein R 1  is represented by any of the following structures: 
       
         
           
           
               
               
           
         
       
     
     
         13 . The composition according to  claim 1 , wherein R 1  is morpholine. 
     
     
         14 . The composition according to  claim 1 , wherein W is O or S. 
     
     
         15 . The composition according to  claim 1 , wherein W is O. 
     
     
         16 . The composition according to  claim 1 , wherein X is CH. 
     
     
         17 . The composition according to  claim 1 , wherein R 3  is H. 
     
     
         18 . The composition according to  claim 1 , wherein L is methylene. 
     
     
         19 . The composition according to  claim 1 , wherein Y contains two heteroatoms. 
     
     
         20 . The composition according to  claim 1 , wherein Y is selected from: 
       
         
           
           
               
               
           
         
       
       wherein:
 A is selected from O, S, NR 4  or optionally substituted C 1 -C 3  alkylene, C 2 -C 3  alkenylene or C 2 -C 3  alkynylene; 
 B is NR 4 , O or CH 2 ; 
 wherein R 4  is H or optionally substituted C 1 -C 10  alkyl, C 2 -C 10  alkenyl or C 2 -C 10  alkynyl; 
 p is selected from 0 or 1; 
 each m is independently selected from 0, 1 or 2; and 
 each n is independently selected from 1, 2 or 3. 
 
     
     
         21 . The composition according to  claim 20 , wherein A is methylene. 
     
     
         22 . The composition according to  claim 20 , wherein B is O. 
     
     
         23 . A composition according to  claim 1 , wherein the compound according to formula I is illustrated by any one of the following structures: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         24 .- 28 . (canceled) 
     
     
         29 . A method for the manufacture of a pharmaceutical composition, according to  claim 1 , comprising:
 a) mixing a compound according to formula I with at least one pharmaceutical excipient selected from the group consisting of fillers, binders, disintegrants, glidants and lubricants to form a blend;   b) processing the blend into a pharmaceutical composition; and   c) compressing the composition of step (b) in to a tablet.   
     
     
         30 . The method of  claim 29 , wherein step (b) further comprises screening to ensure a particle size of less than 500 μm.

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