Patent EA-004398-B1 (EA)
Title: Mono- and disubstituted 3-propyl gamma-aminobutyric acids
Inventor: BELLIOTTI THOMAS RICHARD
IPC: A61P43/00
Filed: 2000-05-31
Abstract: 1. A compound of Formula I or a pharmaceutically acceptable salt thereof, wherein: R<1> is hydrogen, straight or branched alkyl of from 1 to 6 carbon atoms or phenyl; R<2> is straight or branched alkyl of from 4 to 8 carbon atoms; straight or branched alkyl of from 1 to 8 carbon atoms, in which from 1 to 3 hydrogen atoms on alkyl can be substituted with 1-3 fluorine atoms, straight or branched alkenyl of from 2 to 8 carbon atoms, cycloalkyl of from 3 to 7 carbon atoms, alkoxy of from 1 to 6 carbon atoms, cycloalkylalkyl, alkoxyalkyl, OH-alkyl, phenylalkyl, phenoxyalkyl or phenyl substituted with 1-3 groups, each independently selected from halogen, alkoxy, alkyl and amino. 2. A compound according to Claim 1, wherein R<1> is hydrogen and R<2> is straight or branched alkyl of from 4 to 8 carbon atoms. 3. A compound according to Claim 1 or a pharmaceutically acceptable salt thereof selected from: 3-Aminomethyl-5-methyl-nonanoic acid; 3-Aminomethyl-5-methyl-decanoic acid; 3-Aminomethyl-5-methylheptanoic acid; 3-Aminomethyl-5-methyl-undecanoic acid; 3-Aminomethyl-5-methyl-dodecanoic acid; 3-Aminomethyl-5-methyl-tridecanoic acid; 3-Aminomethyl-5-cyclopropyl-hexanoic acid; 3-Aminomethyl-5-cyclobutyl-hexanoic acid; 3-Aminomethyl-5-trifluoromethyl-hexanoic acid; 3-Aminomethyl-5-(2-chlorophenyl)-hexanoic acid; 3-Aminomethyl-5-(3-chlorophenyl)-hexanoic acid; 3-Aminomethyl-5-(4-chlorophenyl)-hexanoic acid; 3-Aminomethyl-5-(2-methoxyphenyl)-hexanoic acid; 3-Aminomethyl-5-(3-methoxyphenyl)-hexanoic acid; 3-Aminomethyl-5-(4-methoxyphenyl)-hexanoic acid; 3-Aminomethyl-5-(phenylmethyl)-hexanoic acid. 4. A compound according to Claim 1 and pharmaceutically acceptable salt thereof, wherein said compound is selected from: (3R, 5R)-3-aminomethyl-5-methyl-oktanoic acid; 3-aminomethyl-5-methyl-oktanoic acid; 3-aminomethyl-4-isopropyl-heptanoic acid; or (3R, 4R, 5R)-3-aminomethyl-4,5-dimethyl-otanoic acid; 5. A compound according to Claim 1 and pharmaceutically acceptable salt thereof, wherein said compound is selected from: (3S, 5R)-3-aminomethyl-5-methyl-nonanoic acid; (3S, 5R)-3-aminomethyl-5-methyl-dekanoic acid; (3S, 5R)-3-aminomethyl-5-methyl-undekanoic acid or (3S, 5R)-3-aminomethyl-5-methyl-dodekanoic acid. 6. A compound of Claim 1 selected from: (3S, 5R)-3-aminomethyl-5, 9-dimethyl-dekanoic acid; (3S, 5R)-3-aminomethyl-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-5, 7-dimethyl-oktanoic acid; (3S, 5R)-3-aminomethyl-5, 10-dimethyl-undecanoic acid; (3S, 5R)-3-aminomethyl-6-cyclopropyl-5-methyl-hexanoic acid; (3S, 5R)-3-aminomethyl-6-cyclobutyl-5-methyl-hexanoic acid; (3S, 5R)-3-aminomethyl-6-cyclopentyl-5-methyl-hexanoic acid; (3S, 5R)-3-aminomethyl-6-cyclohexyl-5-methyl-hexanoic acid; (3S, 5R)-3-aminomethyl-7-cyclopropyl-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-7-cyclobutyl-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-7-cyclopentyl-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-7-cyclohexyl-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-8-cyclopropyl-5-methyl-octanoic acid; (3S, 5R)-3-aminomethyl-8-cyclobutyl-5-methyl-octanoic acid; (3S, 5R)-3-aminomethyl-8-cyclopentyl-5-methyl-octanoic acid; (3S, 5R)-3-aminomethyl-8-cyclohexyl-5-methyl-octanoic acid; (3S, 5R)-3-aminomethyl-6-fluoro-5-methyl-oktanoic acid; (3S, 5R)-3-aminomethyl-9-fluoro-5-methyl-nonanoic acid. 7. A compound of Claim 1 selected from: (3S, 5S)-3-aminomethyl-5-methoxy-hexanoic acid; (3S, 5S)-3-aminomethyl-5-ethoxy-hexanoic acid; (3S, 5S)-3-aminomethyl-5-propoxy-hexanoic acid; (3S, 5S)-3-aminomethyl-5-isopropoxy-hexanoic acid; (3S, 5S)-3-aminomethyl-5-tert-butoxy-hexanoic acid; (3S, 5S)-3-aminomethyl-5-fluoromethoxy-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(2-fluoro-ethoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(3,3,3-trifluoro-propoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-phenoxy-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(4-chloro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(3-chloro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(2-chloro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(4-fluoro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(3-fluoro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(2-fluoro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(4-methoxy-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(3-methoxy-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(2-methoxy-phenoxy)-hexanoic acid; (3S,5S)-3-aminomethyl-5-(4-nitro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(3-nitro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-(2-nitro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-6-propoxy-hexanoic acid; (3S, 5S)-3-aminomethyl-6-isopropoxy-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-tert-butoxy-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-fluoromethoxy-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(2-fluoro-ethoxy)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-6-(3,3,3-trifluoro-propoxy)- hexanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-6-phenoxy-hexanoic acid; (3S, 5S)-3-aminomehtyl-6-(4-chloro-phenoxy)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(3-chloro-phenoxy)-5-methyl- hexanoic acid; (3S, 5S)-3-aminomethyl-6-(2-chloro-phenoxy)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomehtyl-6-(4-fluoro-phenoxy)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(3-fluoro-phenoxy)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomehtyl-6-(2-fluoro-phenoxy)-5-mehtyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(4-methoxy-phenoxy)-5-methyl- hexanoic acid; (3S, 5S)-3-aminomethyl-6-(3-methoxy-phenoxy)-5-methyl- hexanoic acid; (3S, 5S)-3-aminomethyl-6-(2-methoxy-phenoxy)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-6-(4-trifluoromethyl-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-6-(3-trifluoromethyl-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-6-(2-trifluoromethyl-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-6-(4-nitro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-6-(3-nitro-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-5-methyl6-(2-nitor-phenoxy)-hexanoic acid; (3S, 5S)-3-aminomethyl-6-benzyloxy-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-7-hydroxy-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-methoxy-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-7-propoxy-heptanoic acid; (3S, 5S)-3-aminomethyl-7-isopropoxy-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-tert-butoxy-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-fluoromethoxy-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-(2-fluoro-ethoxy)-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-7-(3,3,3-trifluoro-propoxy)-heptanoic acid; (3S, 5S)-3-aminomethyl-7-benzyloxy-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-7-phenoxy-heptanoic acid; (3S, 5S)-3-aminomethyl-7-(4-chloro-phenoxy)-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-(3-chloro-phenoxy)-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-(2-chloro-phenoxy)-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-(4-fluoro-phenoxy)-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-(3-fluoro-phenoxy-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-(2-fluoro-phenoxy)-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-(4-methoxy-phenoxy)-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-(3-methoxy-phenoxy)-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-7-(2-methoxy-phenoxy)-5-methyl-heptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-7-(4-trifluoromethyl-phenoxy)-heptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-7-(3-tirfluoromehtyl-phenoxy)-heptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-7-(2-trifluoromethyl-phenoxy)-heptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-7-(4-nitro-phenoxy)-heptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-7-(3-nitro-phenoxy)-heptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-7-(2-nitro-phenoxy)-heptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-6-phenyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(4-chloro-phenyl)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(3-chloro-phenyl)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(2-chloro-phenyl)-5-mehtyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(4-methoxy-phenyl)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(3-methoxy-phenyl)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(2-methoxy-phenyl)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(3-fluoro-phenyl)-5-methyl-hexanoic acid; (3S, 5S)-3-aminomethyl-6-(2-fluoro-phenyl)-5-methyl-hexanoic acid; (3S, 5R)-3-aminomethyl-5-methyl-7-phenyl-heptanoic acid; (3S, 5R)-3-aminomethyl-7-(4-chloro-phenyl)-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-7-(3-chloro-phenyl)-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-7-(2-chloro-phenyl)-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-7-(4-methoxy-phenyl)-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-7-(3-methoxy-phenyl)-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-7-(2-methoxy-phenyl)-5-methyl-heptanoic acid; (3S, 5R)-3-aminomethyl-7-(4-fluoro-phenyl)-5-methylheptanoic acid; (3S, 5R)-3-Aminomethyl-7-(3-fluoro-phenyl)-5-methylheptanoic acid; (3S, 5R)-3-Aminomethyl-7-(2-fluoro-phenyl)-5-methylheptanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-hept-6-enoic acid; (3S, 5R)-3-aminomethyl-5-methyl-oct-7-enoic acid; (3S, 5R)-3-aminomethyl-5-methyl-non-8-enoic acid; (E)- (3S, 5S)-3-aminomethyl-5-methyl-oct-6-enoic acid; (Z)-(3S, 5S)-3-aminomethyl-5-methyl-oct-6-enoic acid; (Z)-(3S, 5S)-3-aminomethyl-5-methyl-non-6-enoic acid; (E)-(3S, 5S)-3-aminomethyl-5-methyl-non-6-enoic acid; (E)-(3S, 5R)-3-aminomethyl-5-methyl-non-7-enoic acid; (Z)-(3S, 5R)-3-aminomethyl-5-methyl-non-7-enoic acid; (Z)-(3S, 5R)-3-aminomethyl-5-methyl-dec-7-enoic acid; (E)-(3S, 5R)-3-aminomethyl-5-methyl-undec-7-enoic acid; (3S, 5S)-3-aminomethyl-5,6,6-trimethyl-heptanoic acid; (3S, 5S)-3-aminomethyl-5-cyclopropyl-hexanoic acid; (3S, 5S)-3-aminomethyl-5-cyclobutyl-hexanoic acid; (3S,5R)-3-aminomethyl-5-methyl-8-phenyl-octanoic acid; (3S, 5S)-3-aminomethyl-5-methyl-6-phenyl-hexanoic acid and (3S, 5R)-3-aminomethyl-5-methyl-7-phenyl-heptanoic acid. 8. A pharmaceutical composition comprising a ther