Tartaric acid analogs and uses thereof
Provided herein are tartaric acid analogs represented by the following structural formula: or a pharmaceutically acceptable salt thereof, wherein values for the variables (e.g., A, R) are as described herein. Compounds of structural formula I and pharmaceutically acceptable salts thereof are believed to be useful in overcoming tumor resistance and promoting an immune response. Accordingly, also provided herein are various methods involving compounds of structural formula I, e.g., methods of treating a cancer in a subject in need thereof.
1 . A compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
A is *—OC(O)— or *—O(CH 2 )—;
* indicates the point of attachment of A to R;
R is (C 2 -C 8 )alkyl or (C 2 -C 8 )alkenyl substituted with one or more groups independently selected from (C 6 -C 15 )aryl or (C 5 -C 15 )heteroaryl; and
wherein each alkyl and alkenyl is optionally and independently further substituted with one or more fluoro, and each aryl and heteroaryl is optionally and independently substituted with one or more R 2 independently selected from halo, (C 1 -C 3 )alkoxy, (C 1 -C 3 )haloalkoxy, (C 1 -C 3 )alkyl or (C 1 -C 3 )haloalkyl.
2 . The compound of claim 1 , represented by the following structural formula:
or a pharmaceutically acceptable salt thereof.
3 . The compound of claim 1 , represented by the following structural formula:
or a pharmaceutically acceptable salt thereof.
4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is *—OC(O)—.
5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is *—O(CH 2 )—.
6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R is (C 2 -C 5 )alkyl or (C 2 -C 5 )alkenyl substituted with one or more groups independently selected from (C 6 -C 15 )aryl or (C 5 -C 15 )heteroaryl.
7 . The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein R is (C 2 -C 5 )alkyl substituted with one or two groups independently selected from (C 6 -C 15 )aryl or (C 5 -C 15 )heteroaryl.
8 . The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein R is (C 2 -C 3 )alkyl substituted with one or two groups independently selected from (C 6 -C 15 )aryl or (C 5 -C 15 )heteroaryl.
9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each (C 6 -C 15 )aryl is independently selected from phenyl or fluorenyl.
10 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each (C 5 -C 15 )heteroaryl is independently selected from pyridinyl, pyrimidinyl or carbazolyl.
11 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each aryl and heteroaryl is optionally and independently substituted with one or more R 2 independently selected from halo, (C 1 -C 3 )alkoxy, (C 1 -C 3 )fluoroalkoxy, (C 1 -C 3 )alkyl or (C 1 -C 3 )fluoroalkyl.
12 . The compound of claim 1 , represented by one of the following structural formulas:
or a pharmaceutically acceptable salt of any of the foregoing.
13 . The compound of claim 12 , represented by the following structural formula:
or a pharmaceutically acceptable salt thereof.
14 . The compound of claim 12 , represented by the following structural formula:
or a pharmaceutically acceptable salt thereof.
15 . The compound of claim 12 , represented by the following structural formula:
or a pharmaceutically acceptable salt thereof.
16 . A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.