PHENYL TRIAZOLE MLL1-WDR5 PROTEIN-PROTEIN INTERACTION INHIBITOR
Described herein are a phenyl triazole MLL1-WDR5 protein-protein interaction inhibitors, pharmaceutical compositions and methods of use.
1 . A compound having a structure of Formula I, Formula II, Formula III, Formula IV, Formula V or Formula VI, or a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof, as described in the specification.
2 . The compound of claim 1 , wherein the compound has a structure of Formula I, wherein the compound is selected from Table 1, or a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof.
3 . The compound of claim 1 , wherein the compound has a structure of Formula II or Formula III, wherein the compound is selected from Table 1, or a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof.
4 . The compound of claim 1 , wherein the compound has a structure of Formula III, wherein the compound is selected from Table 2, or a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof.
5 . The compound of claim 1 , wherein the compound has a structure of Formula I or Formula III, wherein the compound is selected from Table 2, or a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof.
6 . The compound of claim 1 , wherein the compound has a structure of Formula IV, wherein the compound is selected from Table 3, or a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof.
7 . The compound of claim 1 , wherein the compound has a structure of Formula V, wherein the compound is selected from Table 3, or a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof.
8 . The compound of claim 1 , wherein the compound has a structure of Formula VI, wherein the compound is selected from Table 3, or a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof.
9 . The compound of claim 1 , wherein the compound does not have the structure of DDO-2093.
10 . The compound of claim 1 , wherein the compound does not have the structure of DDO-2213.
11 . The compound of claim 1 , wherein the compound has the formula:
or a pharmaceutically acceptable salt thereof.
12 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof, and a pharmaceutically acceptable excipient.
13 . A method for the treatment or prevention of acute leukemia in a patient in need thereof, comprising administering to the patient a therapeutically acceptable dose of the compound of claim 1 , or the pharmaceutical composition of claim 12 .
14 . The method of claim 13 , wherein the acute leukemia is acute leukemia with MLL1 gene rearrangement.