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US 2008/0293753 A1Published application
Novel Compounds
AssigneeGlaxo Group Limited
InventorsGiuseppe Alvaro, David Amantini, Markus Bergauer, Francesca Bonetti, Roberto Profeta
Life of this patent
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Abstract
The invention relates to quaternary α-aminocarboxyamide derivatives of formula (I), wherein R1, R2, R3, R4, R5, R6, X, q and n are as defined in claim 1, for treating diseases and conditions mediated by modulation of voltage-gated sodium channels.
Claims27
A compound of formula (I), a pharmaceutically acceptable salt, solvate, or prodrug thereof:
- wherein
- R1 and R2 are independently hydrogen, C1-6alkyl or C3-6cycloalkylC1-6alkyl;
- or such R1 and R2, together with the nitrogen to which they are attached, may form an unsubstituted 3-, 4-, 5- or 6-membered saturated ring;
- R3 is C1-6alkyl, C1-6haloalkyl, C1-3alkenyl, C1-3alkoxyC1-3alkyl, C1-3haloalkoxyC1-3alkyl or (CH2)tOH;
- or such R1 and R3, together with the interconnecting atoms, form a saturated or unsaturated 5- to 7-membered ring, with the proviso that there is only one heteroatom in the ring, which must be Nitrogen;
- X is carbon or nitrogen;
- n is 0, 1 or 2, wherein when present each R4 is independently selected from the list consisting of C1-3alkyl, halogen, cyano, haloC1-3alkyl, hydroxy, C1-3alkoxy and C1-3haloalkoxy,
- q is 1 or 2;
- t is 1 or 2;
- either R5 or R6 is —O—R7 or —OCH2R7, wherein the other R5 or R6 is hydrogen or R4;
- and wherein R7 is either a phenyl ring or a 5- or 6-membered aromatic heterocyclic ring (independently containing one or more nitrogen, sulphur or oxygen atoms) wherein either the phenyl ring or the heterocyclic ring is optionally substituted by one or more groups independently selected from the list consisting of —C1-3alkyl, halogen, cyano, haloC1-3alkyl, hydroxy, C1-3alkoxy and C1-3haloalkoxy.
8 more elements
A compound according to any preceding claim wherein R5 is —O—R7 or —OCH2R7, and R6 is hydrogen or R4;
- and wherein R7 is either a phenyl ring or a 5- or 6-membered aromatic heterocyclic ring (independently containing one or more nitrogen, sulphur or oxygen atoms) wherein either the phenyl ring or the heterocyclic ring is optionally substituted by one or more groups independently selected from the list consisting of C1-3alkyl, halogen, cyano, haloC1-3alkyl, hydroxy, C1-3alkoxy and C1-3haloalkoxy.
A compound according to any preceding claim wherein R1 and R3, together with the interconnecting atoms, forms a 5-membered pyrrolidinone ring.
A compound of formula (I) which is:
- (5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-methyl-L-prolinamide;
- (5R)-5-(4-{[(2-cyanophenyl)methyl]oxy}phenyl)-2-methyl-L-prolinamide;
- (5R)-5-{4-[(2-cyanophenyl)oxy]phenyl}-2-methyl-L-prolinamide;
- (5S)-2-methyl-5-{4-[(phenylmethyl)oxy]phenyl}-D-prolinamide;
- (5S)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-methyl-D-prolinamide;
- (2R,5R)-2-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-1,7-diazaspiro[4.4]nonan-6-one;
- 2-[({4-[(2R,5R)-6-oxo-1,7-diazaspiro[4.4]non-2-yl]phenyl}oxy)methyl]benzonitrile;
- 2-({4-[(2R,5R)-6-oxo-1,7-diazaspiro[4.4]non-2-yl]phenyl}oxy)benzonitrile;
- (2R,5R)-2-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;
- (2R,5R)-2-(3-{[(2-fluorophenyl)methyl]oxy}phenyl)-1,7-diazaspiro[4,4]nonan-6-one;
- (2R,5R)-2-(3-{[(2-fluorophenyl)methyl]oxy}phenyl)-7-methyl-1,7-diazaspiro[4.4]nonan-6-one;
- (2R,5R)-2-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-1,7-diazaspiro[4.6]undec-9-en-6-one;
- (2R,5S)-2-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-1,7-diazaspiro[4.5]decan-6-one;
- (2S,5S)-2-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-1,7-diazaspiro[4.5]decan-6-one;
- (5R)-5-[4-{[(2-fluorophenyl)methyl]oxy}-3-(methyloxy)phenyl]-2-methyl-L-prolinamide;
- (5R)-5-[4-{[(2-fluorophenyl)methyl]oxy}-3-(methyloxy)phenyl]-2-[(methyloxy)methyl]-L-prolinamide;
- (5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-[(methyloxy)methyl]-L-prolinamide;
- (5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-(hydroxymethyl)-L-prolinamide;
- (2S,5S)-2-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-1,7-diazaspiro[4.4]nonan-6-one;
- (5R,7R)-7-(4-{[(2-Fluorophenyl)methyl]oxy}phenyl)-2,6-diazaspiro[4.5]decan-1-one;
- and
- (5S,7S)-7-(4-{[(2-Fluorophenyl)methyl]oxy}phenyl)-2,6-diazaspiro[4.5]decan-1-one;
- or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
20 more elements
Dependencies are inferred from the claim text.