Nitrocatechol derivatives as COMT inhibitors

• US 9,550,759 B2
• Filed: 11/14/2014
• Issued: 01/24/2017
• Est. Priority Date: 07/26/2005
• Status: Active Grant

• Current Assignee: BIAL Portela & Ca, SA
• Original Assignee: BIAL Portela & Ca, SA
• Inventors: Learmonth, David Alexander, Palma, Pedro Nuno Leal, Kiss, Laszlo Erno, Ferreira, Humberto Dos Santos, Soares Da Silva, Patricio Manuel Vieira Araujo
• Primary Examiner(s): HAVLIN, ROBERT H
• Application Number:
  US14/541,654
• Publication Number:
  US 20150072977A1
• Time in Patent Office: 802 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• 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 27/02 Ophthalmic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 213/89 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 215/60 N-oxides
• CPC Class Codes: C07D 271/06 1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
• CPC Class Codes: C07D 271/107 with two aryl or substituted aryl radicals attached in positions 2 and 5
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/04 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 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/04 : directly linked by a ring-member-to-ring-member bond

Abstract

New compounds of formula I are described. The compounds have potentially valuable pharmaceutical properties in the treatment of some central and peripheral nervous system disorders.

Claims

1. A method of increasing the amount of orally administered L-DOPA which reaches the brain of a patient afflicted by Parkinson'"'"'s disease and thereby treating Parkinson'"'"'s disease which comprises administering orally to said patient a COMT-inhibitory effective amount of a compound of the Formula (I):

2. A method as claimed in claim 1, wherein the compound of Formula (I) is 5-[3-(2,5-dichloro-4,6-dimethyl-1-oxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-3-nitrobenzene-1,2-diol.

3. A method of inhibiting COMT in the periphery which comprises the administration to a patient in need thereof a COMT-inhibitory amount of a compound of the Formula (I):

4. A method as claimed in claim 3, wherein the compound of Formula (I) is 5-[3-(2,5-dichloro-4,6-dimethyl-1-oxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-3-nitrobenzene-1,2-diol.

5. A method of manufacture of a pharmaceutical composition suitable for the treatment of Parkinson'"'"'s disease which comprises formulating a compound of the Formula (I):

6. A method as claimed in claim 5, wherein the compound of the Formula (I) is 5-[3-(2,5-dichloro-4,6-dimethyl-1-oxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-3-nitrobenzene-1,2-diol.

7. A method of reducing O-methylation of L-DOPA in a patient suffering from Parkinson'"'"'s disease treated with L-DOPA which comprises the administration of a compound of the Formula (I):

8. A method as claimed in claim 7, wherein the compound of the Formula (I) is 5-[3-(2,5-dichloro-4,6-dimethyl-1-oxy-pyridin-3-yl)-[1,2,4]oxadiazol-5-yl]-3-nitrobenzene-1,2-diol.