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US 8,299,071 B2Granted
Substituted pyridine derivatives
AssigneeH. Lundbeck A/S
InventorsChristian Wenzel Tornoe, Nikolay Khanzhin, Mario Rottlander, William Patrick Watson, Daniel Rodriguez Greve
Life of this patent
Estimating the term…
Abstract
The present invention relates to pyridine derivatives of the general formula (I) and their use as openers of the KCNQ family potassium ion channels for the treatment of CNS disorders.
Claims18
A method of ameliorating or inhibiting a disease selected from the group consisting of epilepsy, bipolar disorder, neuropathic pain and migraine pain comprising administering a compound of formula I:
- wherein:
- q is 0 or 1;
- each of R1 and R2 is independently selected from the group consisting of halogen, cyano, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy, C3-8-cycloalk(en)yloxy and C3-8-Cycloalk(en)yl-C1-6-alk(en/yn)yloxy;
- and
- R3 is selected from the group consisting of C1-8-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, optionally substituted aryl-C1-6-alk(en/yn)yl, optionally substituted aryl-C3-8-cycloalk(en)yl, optionally substituted aryl-C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yl-C3-8-heterocycloalk(en)yl-C1-6-alk(en/yn)yl, C3-8-heterocycloalk(en)yl-C1-6-alk(en/yn)yl, heteroaryl-C1-6-alk(en/yn)yl, heteroaryl-C3-8-cycloalk(en)yl, heteroaryl-C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, NR4R5—C1-6-alk(en/yn)yl, NR4R5—C3-8-cycloalk(en)yl, NR4R5—C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, C1-6-alk(en/yn)yloxy -C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yloxy-C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yloxy-C1-6-alk(en/yn)yl, halo-C1-6-alk(en/yn)yl, halo-C3-8-cycloalk(en)yl and halo-C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, wherein:
- each of R4 and R5 is independently selected from the group consisting of hydrogen, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl;
- or a pharmaceutically acceptable salt thereof to a subject in need thereof.
4 more elements
A method of ameliorating or inhibiting a disease selected from the group consisting of epilepsy, bipolar disorder, neuropathic pain and migraine pain comprising administering a compound selected from the group consisting of:
- (2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-carbamic acid benzyl ester;
- (2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-carbamic acid 2-chloro-benzyl ester;
- 2-(4-Chloro-phenyl)-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide;
- 2-Phenyl-cyclopropanecarboxylic acid(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-thiophen-2-yl-acetamide;
- 3-Cyclohexyl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-propionamide;
- (2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-carbamic acid isobutyl ester;
- 3-(3-Chloro-phenyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-propionamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(3,5-dimethyl-phenyl)-acetamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-3-p-tolyl-propionamide;
- 2-(3-Chloro-phenyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide;
- 2-(3,4-Dichloro-phenyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-thiophen-3-yl-acetamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-p-tolyl-acetamide;
- 2-(3-Bromo-phenyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(3-trifluoromethyl-phenyl)-acetamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-phenyl-acetamide;
- 3,5,5-Trimethyl-hexanoic acid(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide;
- Octanoic acid(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-naphthalen-2-yl-acetamide;
- Heptanoic acid(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(3,4-dimethyl-phenyl)-acetamide;
- 2-Cyclohex-1-enyl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(4-methoxy-3-methyl-phenyl)-acetamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(4-methoxy-phenyl)-acetamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-3-(4-methoxy-phenyl)-propionamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-m-tolyl-acetamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(4-fluoro-phenyl)-acetamide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-3,3-dimethyl-butyramide;
- N-(2,4-Dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(3-fluoro-phenyl)-acetamide;
- 2-Bicyclo[2.2.1]kept-2-yl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide;
- 2-(3,4-Difluoro-phenyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide;
- 4-Methyl-pentanoic acid(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide;
- 2-(Cyclopent-2-enyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide;
- 2-Cyclohexyl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide;
- 5-Methyl-hexanoic acid(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide;
- 2-Cyclopentyl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide;
- 3-Cyclopentyl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-propionamide;
- Hexanoic acid(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide;
- N-(4-Chloro-2-methoxy-6-morpholin-4-yl-pyridin-3-yl)-2-cyclopentylacetamide;
- N-(2-Chloro-4-methoxy-6-morpholin-4-yl-pyridin-3-yl)-2-cyclopentylacetamide;
- N-(2-Chloro-4-methoxy-6-morpholin-4-yl-pyridin-3-yl)-3,3-dimethylbutyramide;
- N-(4-Chloro-2-methoxy-6-morpholin-4-yl-pyridin-3-yl)-3,3-dimethylbutyramide;
- and
- N-(4-Chloro-2-methoxy-6-morpholin-4-yl-pyridin-3-yl)-propionamide;
- or pharmaceutically acceptable salt thereof to a subject in need thereof.
43 more elements
Dependencies are inferred from the claim text.