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US 2003/0195251 A1Published application
Amino acids with affinity for the alpha-2-delta-protein
AssigneeWarner-Lambert Company
InventorsNancy Sue Barta, Jacob Bradley Schwarz, Andrew John Thorpe, David Juergen Wustrow
Life of this patent
Estimating the term…
Abstract
This invention relates to certain β-amino acids that bind to the alpha-2-delta (α2δ) subunit of a calcium channel. These compounds and their pharmaceutically acceptable salts are useful in the treatment of a variety of psychiatric, pain and other disorders.
Claims14
This invention relates to compounds of the formula I
- 18
- wherein
- R1 is hydrogen or (C1-C6)alkyl optionally substituted with from one to five fluorine atoms;
- R2 is hydrogen or (C1-C6)alkyl optionally substituted with from one to five fluorine atoms;
- or
- R1 and R2, together with the carbon to which they are attached, form a three to six membered cycloalkyl ring;
- R3 is (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C3)alkyl, phenyl, phenyl-(C1-C3)alkyl, pyridyl, pyridyl-(C1-C3)alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms, preferably with from zero to three fluorine atoms, and wherein said phenyl and said pyridyl and the phenyl and pyridyl moieties of said phenyl-(C1-C3)alkyl and said pyridyl-(C1-C3)alkyl, respectively, can be optionally substituted with from one to three substituents, preferably with from zero to two substituents, independently selected from chloro, fluoro, amino, nitro, cyano, (C1-C3)alkylamino, (C1-C3)alkyl optionally substituted with from one to three fluorine atoms and (C1-C3)alkoxy optionally substituted with from one to three fluorine atoms;
- R4 is hydrogen or (C1-C6)alkyl optionally substituted with from one to five fluorine atoms;
- R5 is hydrogen or (C1-C6)alkyl optionally substituted with from one to five fluorine atoms;
- and
- R6 is hydrogen or (C1-C6)alkyl;
- or a pharmaceutically acceptable salt of such compound.
9 more elements
A compound of the formula II:
- 20
- wherein R1 is hydrogen or (C1-C3)alkyl optionally substituted with from one to five fluorine atoms;
- R2 is hydrogen or (C1-C3)alkyl optionally substituted with from one to five fluorine atoms;
- R3 is (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C3)alkyl, phenyl, phenyl-(C1-C3)alkyl, pyridyl, pyridyl-(C1-C3)alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms, preferably with from zero to three fluorine atoms, and wherein said phenyl and said pyridyl and the phenyl and pyridyl moieties of said phenyl-(C1-C3)alkyl and said pyridyl-(C1-C3)alkyl, respectively, can be optionally substituted with from one to three substituents, preferably with from zero to two substituents, independently selected from chloro, fluoro, amino, nitro, cyano, (C1-C3)alkylamino, (C1-C3)alkyl optionally substituted with from one to three fluorine atoms and (C1-C3)alkoxy optionally substituted with from one to three fluorine atoms;
- with the proviso that when R1 is hydrogen, R2 is not hydrogen;
- or a pharmaceutically acceptable salt of such compound.
3 more elements
A compound of the formula III
- 24
- wherein R3 is wherein R3 is (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C3)alkyl, phenyl, phenyl-(C1-C3)alkyl, pyridyl, pyridyl-(C1-C3)alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms, preferably with from zero to three fluorine atoms, and wherein said phenyl and said pyridyl and the phenyl and pyridyl moieties of said phenyl-(C1-C3)alkyl and said pyridyl-(C1-C3)alkyl, respectively, can be optionally substituted with from one to three substituents, preferably with from zero to two substituents, selected from chloro, fluoro, amino, nitro, cyano, (C1-C3)alkylamino, (C1-C3)alkyl optionally substituted with from one to three fluorine atoms and (C1-C3)alkoxy optionally substituted with from one to three fluorine atoms;
- or a pharmaceutically acceptable salt thereof.
A compound of the formula IV
- 25
- wherein R1 is hydrogen or (C1-C6)alkyl optionally substituted with from one to five fluorine atoms;
- and
- R3 is wherein R3 is (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C3)alkyl, phenyl, phenyl-(C1-C3)alkyl, pyridyl, pyridyl-(C1-C3)alkyl, phenyl-N(H)—, or pyridyl-N(H)—, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms, preferably with from zero to three fluorine atoms, and wherein said phenyl and said pyridyl and the phenyl and pyridyl moieties of said phenyl-(C1-C3)alkyl and said pyridyl-(C1-C3)alkyl, respectively, can be optionally substituted with from one to three substituents, preferably with from zero to two substituents, selected from chloro, fluoro, amino, nitro, cyano, (C1-C3)alkylamino, (C1-C3)alkyl optionally substituted with from one to three fluorine atoms and (C1-C3)alkoxy optionally substituted with from one to three fluorine-atoms;
- or a pharmaceutically acceptable salt of such compound.
2 more elements
A compound or salt selected from the following compounds and their pharmaceutically acceptable salts:
- 3-Amino-5-methyl-octanoic acid;
- 3-Amino-5-methyl-nonanoic acid;
- (3S,5R)-3-Amino-5-methyl-heptanoic acid;
- (3S,5R)-3-Amino-5-methyl-octanoic acid;
- (3S,5R)-3-Amino-5-methyl-nonanoic acid;
- 3-Amino-7-cyclopentyl-5-methyl-heptanoic acid;
- 3-Amino-7-cyclohexyl-5-methyl-heptanoic acid;
- (3S,5R)-3-Amino-7-cyclopentyl-5-methyl-heptanoic acid;
- (3S,5R)-3-Amino-7-cyclohexyl-5-methyl-heptanoic acid;
- 3-Amino-5-methyl-7-phenyl-heptanoic acid;
- 3-Amino-5-methyl-7-(2,4-difluoro-phenyl)-heptanoic acid;
- 3-Amino-8-(2,3-difluoro-phenyl)-5-methyl-octanoic acid;
- 3-Amino-8-(2,4-difluoro-phenyl)-5-methyl-octanoic acid;
- 2-Aminomethyl-4-methyl-heptanoic acid;
- (2R, 4R)-2-Aminomethyl-4-methyl-heptanoic acid
- (2R, 4S)-2-Aminomethyl-4-methyl-heptanoic acid;
- 2-Aminomethyl-3-[1-4-methyl-pentyl)-cyclopropyl]-propionic acid;
- 2-Aminomethyl-4-ethyl-8-methyl-nonanoic acid;
- 2-Aminomethyl-3-(1-methyl-cyclopropy)-propionic acid;
- 2-Aminomethyl-4,4-dimethyl-8-methyl-nonanoic acid;
- 2-Aminomethyl-4-cyclohexyl-3-methyl-butyric acid;
- and
- 2-Aminomethyl-4,6-dimethyl-heptanoic acid.
20 more elements
Dependencies are inferred from the claim text.