Therapeutically active compositions and their methods of use

Patent metadata

Field	Value
Publication number	US-10640534-B2
Application number	US-201715809325-A
Country	US
Kind code	B2
Filing date	Nov 10, 2017
Priority date	Jan 19, 2012
Publication date	May 5, 2020
Grant date	May 5, 2020

Abstract

Provided are methods of treating a cancer characterized by the presence of a mutant allele of IDH1/2 comprising administering to a subject in need thereof a compound described here.

First claim

The invention claimed is:

1. A method of making a compound of structural formula (A) or a pharmaceutically acceptable salt, tautomer or hydrate thereof, wherein:

R 1 is optionally substituted C 4 -C 6 carbocyclyl;
each R 2 and R 3 is independently selected from optionally substituted aryl or optionally substituted heteroaryl;
R 4 is optionally substituted aryl or optionally substituted heteroaryl,
n is 1 or 2; and
X is —CH 2 —, O, —NH—, —CH(OH)—, or —CH(F)—,

the method comprising:
reacting a compound of formula B:

with R 4 —Br under Buchwald conditions to provide the compound of structural formula (A).

2. The method of claim 1 wherein the Buchwald conditions comprise use of a palladium catalyst, a ligand and a base in an organic solvent.

3. The method of claim 2 wherein the solvent is dioxane, the palladium catalyst is Pd 2 (dba) 3 , the ligand is Xphos and the base is cesium carbonate.

4. A method of making a compound of structural formula (B) or a pharmaceutically acceptable salt, tautomer, or hydrate thereof,

the method comprising:
reacting a compound of structural formula (C):

with R 1 NC, R 2 CHO and R 3 —NH 2 under Ugi coupling reaction conditions to provide the compound of structural formula (B).

5. The method of claim 4 wherein the Ugi coupling takes place in a solvent.

6. The method of claim 5 wherein the solvent is methanol.

Assignees

• Agios Pharmaceuticals Inc

Inventors

• Popovici-Muller Janeta
• Lemieux Rene M
• Travins Jeremy
• Cai Zhenwei
• Cui Dawei
• Zhou Ding

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title