Therapeutically active compositions and their methods of use

• US 10,640,534 B2
• Filed: 11/10/2017
• Issued: 05/05/2020
• Est. Priority Date: 01/19/2012
• Status: Active Grant

• Current Assignee: Servier Pharmaceuticals LLC (Servier Sas)
• Original Assignee: Agios Pharmaceuticals Inc.
• Inventors: Popovici-Muller, Janeta, Lemieux, Rene M., Travins, Jeremy, Cai, Zhenwei, Cui, Dawei, Zhou, Ding
• Primary Examiner(s): Jean-Louis, Samira J
• Application Number:
  US15/809,325
• Publication Number:
  US 20180194802A1
• Time in Patent Office: 907 Days
• CPC Class Codes: A61K 38/005 Enzyme inhibitors protease inhibitors A61K38/55
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07D 205/08 with one oxygen atom directly attached in position 2, e.g. beta-lactams
• CPC Class Codes: C07D 207/26 2-Pyrrolidones
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07K 5/06078 : and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/06191 : containing heteroatoms different from O, S, or N

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.

Claims

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

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 Pd₂(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,

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.