Pyrrolopyrimidine derivatives as NR2B NMDA receptor antagonists

• US 10,420,768 B2
• Filed: 04/24/2018
• Issued: 09/24/2019
• Est. Priority Date: 09/15/2014
• Status: Active Grant

• Current Assignee: Rugen Holdings (Cayman) Limited
• Original Assignee: Rugen Holdings (Cayman) Limited
• Inventors: Shapiro, Gideon
• Primary Examiner(s): Rao, Deepak R
• Application Number:
  US15/961,553
• Publication Number:
  US 20180303834A1
• Time in Patent Office: 518 Days
• Field of Search: 544280, 51425505, 5142651
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Disclosed are chemical entities of formula I:

wherein X, Y, Z, R¹, R³, R⁴, R⁵ and R⁶ are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of formula I, and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of formula I.

Claims

1. A chemical entity selected from the group consisting of:

2. The chemical entity of claim 1, wherein the chemical entity is C-179:

3. A pharmaceutical composition comprising the chemical entity of claim 1 and a pharmaceutically acceptable carrier.

4. The pharmaceutical composition of claim 3, which is suitable for oral administration.

5. A method of treating a disease or disorder responsive to NR2B antagonism in a subject in need of such treatment, comprising administering an effective amount of the chemical entity of claim 1, wherein the disease or disorder is depression, a seizure disorder, pain, a movement disorder, Huntington'"'"'s disease, cerebral ischaemia, traumatic brain injury, or a substance abuse disorder.

6. The method of claim 5, wherein the disease or disorder is depression.

7. A pharmaceutical composition comprising the chemical entity of claim 2 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 7, which is suitable for oral administration.

9. A method of treating a disease or disorder responsive to NR2B antagonism in a subject in need of such treatment, comprising administering an effective amount of the chemical entity of claim 2, wherein the disease or disorder is depression, a seizure disorder, pain, a movement disorder, Huntington'"'"'s disease, cerebral ischaemia, traumatic brain injury, or a substance abuse disorder.

10. The method of claim 9, wherein the disease or disorder is depression.