Biphenyl amides with modified ether groups as Hsp90 inhibitors and Hsp70 inducers
Provided herein are compounds of the formulas: wherein: n, X 2 , R 3 , R 3 ′, R 4 , R 4 ′, R 5 , R 5 ′, R 6 , and R 6 ′ are as defined herein. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including diabetic peripheral neuropathy or cancer.
1. A compound of the formula:
wherein:
R 7 is aryl (c≤12) , aralkyl (c≤12) , or a substituted version of either of these groups;
R 8 is hydrogen, alkyl (c≤12) , cycloalkyl (c≤12) , substituted alkyl (c≤12) , or substituted cycloalkyl (c≤12) ;
R 9 is alkyl (c≤12) , cycloalkyl (c≤12) , aryl (c≤12) , heteroaryl (c≤12) , or a substituted version of any of these groups; and
Y 1 and Y 2 are each independently hydrogen or hydroxy;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein the bond between atom 1 and atom 2 in formula II is a single bond.
3. The compound of claim 1 , wherein the bond between atom 1 and atom 2 in formula II is a double bond.
4. The compound of claim 1 , wherein Y 1 is hydrogen.
5. The compound of claim 1 , wherein Y 1 is hydroxy.
6. The compound of claim 1 , wherein Y 2 is hydrogen.
7. The compound of claim 1 , wherein Y 2 is hydroxy.
8. The compound of claim 1 , wherein R 8 is alkyl (C≤12) .
9. The compound of claim 8 , wherein R 8 is methyl.
10. The compound of claim 1 , wherein R 9 is alkyl(C≤12).
11. The compound of claim 10 , wherein R 9 is methyl.
12. The compound of claim 1 , wherein R 7 is aralkyl (c≤12) or substituted aralkyl (c≤12) .
13. The compound of claim 12 , wherein R 7 is aralkyl (c≤12) .
14. The compound of claim 13 , wherein R 7 is benzyl.
15. The compound of claim 12 , wherein R 7 is substituted aralkyl (c≤12) .
16. The compound of claim 15 , wherein R 7 is 4-chlorophenylmethyl, 2-bromophenylmethyl, or 2-methoxyphenylmethyl.
17. The compound of claim 1 , wherein the compound is further defined as:
or a pharmaceutically acceptable salt thereof.
18. A pharmaceutical composition comprising:
(A) a compound of claim 1 ; and
(B) a pharmaceutically acceptable carrier.
19. A method of treating a disease or disorder, wherein the disease or disorder is a neurodegenerative disease associated with Hsp70 or Hsp90 in a patient comprising administering to the patient in need thereof a therapeutically effective amount of a compound of claim 1 .