Granted Patent
B2
US 12,595,278 · App. 18/485,699 · Granted Apr 7, 2026
Biaryl amides with modified sugar groups for treatment of diseases associated with heat shock protein pathway
Inventors:
Xin Jiang (Coppell, TX); Melean Visnick (Irving, TX); Christopher F. Bender (Garland, TX); Gary Bolton (Ann Arbor, MI); Bradley Caprathe (Livonia, MI); Chitase Lee (Ann Arbor, MI)
Assignee:
REATA PHARMACEUTICALS, INC
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Abstract
Provided herein are biaryl amides and coumarin-based compounds with modified sugar groups having the formulas: wherein variables are as defined herein. Pharmaceutical compositions of the compounds are also provided. These biaryl amides and coumarin-based derivatives with modified sugar groups are useful for treatment and prevention of diseases and disorders, including neurological disorders, such as neurodegenerative diseases and nerve damaging disorders, for example, diabetic peripheral neuropathy.
Claims (47)
1 . A method of treating diabetic peripheral neuropathy, in a patient in need thereof comprising administering to the patient in need thereof a therapeutically effective amount of a compound of the formula:
wherein:
n is 1;
Y 1 is -alkanediyl (C≤6) -, —C(O)-alkanediyl (C≤6) -, or a substituted version of any of these groups;
Y 2 is O;
R 3 is —NR 11 R 11 ′ or —C(O)NR 12 R 12 ′, wherein:
R 11 and R 11 ′ are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) , or substituted acyl (C≤6) ;
R 12 and R 12 ′ are each independently hydrogen, alkyl (C≤6) , or substituted alkyl (C≤6) ;
R 7 is alkyl (C≤6) or a substituted alkyl (C≤6) ;
R 8 is hydroxy, alkoxy (C≤6) , or substituted alkoxy (C≤6) ; and
R 9 and R 10 are each hydroxy;
or a pharmaceutically acceptable salt of the formula.
2 . The method of claim 1 , wherein the patient is a mammal.
3 . The method of claim 2 , wherein the patient is human.
4 . The method of claim 1 , wherein the compound is further defined as:
wherein:
n is 1;
R 7 is alkyl (C≤6) or substituted alkyl (C≤6) ;
R 8 is hydroxy, alkoxy (C≤6) , or substituted alkoxy (C≤6) ; and
R 9 and R 10 are each hydroxy;
or a pharmaceutically acceptable salt thereof.
5 . The method of claim 4 , wherein the compound is further defined as:
wherein:
R 7 is alkyl (C≤6) , alkoxy (C≤6) ; and
R 8 is hydroxy alkoxy (C≤6) , or substituted version of any of these groups;
or a pharmaceutically acceptable salt thereof.
6 . The method of claim 4 , wherein the compound is further defined as:
wherein:
R 7 is alkyl (C≤6) , or substituted alkyl (C≤6) ;
R 8 is alkoxy (C≤6) or substituted alkoxy (C≤6) ;
or a pharmaceutically acceptable salt thereof.
7 . The method of claim 4 , wherein the compound is further defined as:
wherein:
R 7 is alkyl (C≤6) or substituted alkyl (C≤6) ;
R 8 is hydroxy;
or a pharmaceutically acceptable salt thereof.
8 . The method of claim 1 , wherein R 7 is alkyl (C≤6) .
9 . The method of claim 1 , wherein R 8 is hydroxy.
10 . The method of claim 1 , wherein R 8 is alkoxy (C≤6) or substituted alkoxy (C≤6) .
11 . The method of claim 1 , wherein the compound is further defined as:
or a pharmaceutically acceptable salt of any of these formulas.
12 . The method of claim 11 , wherein the compound is further defined as:
or a pharmaceutically acceptable salt of either formula.
13 . The method of claim 12 , wherein the compound is further defined as:
or a pharmaceutically acceptable salt thereof.
14 . The method of claim 12 , wherein the compound is further defined as:
or a pharmaceutically acceptable salt thereof.
Continuity (3)
Division
17055331
Provisional Application
62671047
· May 14, 2018
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