Bicyclic γ-amino acid derivative
It is intended to provide a bicyclic γ-amino acid derivative having excellent activity as an α 2 δ ligand. The present invention provides a compound represented by the general formula (I): wherein R 1 , R 2 , R 2′ , R 4 , R 5 , R 6 , R 7 , R 8 , and R 8′ are a hydrogen atom or the like; and R 3 is a hydrogen atom, a halogen atom, a C1-C6 alkyl group, or the like.
1. A compound according to formula (I) or a pharmacologically acceptable salt thereof, wherein formula (I) is selected from the group consisting of:
wherein
R 1 , R 2 , R 2′ , R 4 , R 5 , R 6 , R 7 , R 8 , and R 8′ are a hydrogen atom; and
R 3 is a hydrogen atom, a methyl group or an ethyl group.
2. A pharmacologically acceptable salt of a compound according claim 1 , wherein the pharmacologically acceptable salt is hydrochloride, benzenesulfonate, or p-toluenesulfonate.
3. A compound selected from the group consisting of:
[(1R,5S,6S)-6-(aminomethyl)bicyclo[3.2.0]hept-3-en-6-yl]acetic acid;
[(1R,5S,6S)-6-(aminomethyl)bicyclo[3.2.0]hept-3-en-6-yl]acetic acid hydrochloride;
[(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid;
[(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid p-toluenesulfonate;
and
[(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid benzenesulfonate.
4. [(1R,5S,6S)-6-(aminomethyl)bicyclo [3.2.0]hept-3-en-6-yl]acetic acid.
5. [(1R,5S,6S)-6-(aminomethyl)bicyclo[3.2.0]hept-3-en-6-yl]acetic acid hydrochloride.
6. [(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid p-toluenesulfonate.
7. [(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid benzenesulfonate.
8. A pharmaceutical composition comprising [(1R,5S,6S)-6-(aminomethyl)bicyclo[3.2.0]hept-3-en-6-yl]acetic acid as an active ingredient and a pharmaceutically acceptable additive.
9. A pharmaceutical composition comprising [(1R,5S,6S)-6-(aminomethyl)bicyclo[3.2.0]hept-3-en-6-yl]acetic acid hydrochloride as an active ingredient and a pharmaceutically acceptable additive.
10. A pharmaceutical composition comprising [(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid p-toluenesulfonate as an active ingredient and a pharmaceutically acceptable additive.
11. A pharmaceutical composition comprising [(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid benzenesulfonate as an active ingredient and a pharmaceutically acceptable additive.
12. A method of treating a disease or disorder selected from the group consisting of postherpetic neuralgia, neuropathic pain, diabetic neuropathic pain, and fibromyalgia comprising administering a compound or a pharmacologically acceptable salt thereof selected from the group consisting of [(1R,5S,6S)-6-(aminomethyl)bicyclo[3.2.0]hept-3-en-6-yl]acetic acid; [(1R,5S,6S)-6-(aminomethyl)bicyclo[3.2.0]hept-3-en-6-yl]acetic acid hydrochloride; [(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid p-toluenesulfonate; and [(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid benzenesulfonate.
13. The method according to claim 12 , wherein the disease or disorder is postherpetic neuralgia.
14. The method according to claim 12 , wherein the disease or disorder is neuropathic pain.
15. The method according to claim 12 , wherein the disease or disorder is diabetic neuropathic pain.
16. The method according to claim 12 , wherein the disease or disorder is fibromyalgia.
17. The method according to claim 12 , wherein the compound or the pharmacologically acceptable salt thereof is [(1R,5S,6S)-6-(aminomethyl)bicyclo [3.2.0]hept-3-en-6-yl]acetic acid.
18. The method according to claim 12 , wherein the compound or the pharmacologically acceptable salt thereof is [(1R,5S,6S)-6-(aminomethyl)bicyclo [3.2.0]hept-3-en-6-yl]acetic acid hydrochloride.
19. The method according to claim 12 , wherein the compound or the pharmacologically acceptable salt thereof is [(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid p-toluenesulfonate.
20. The method according to claim 12 , wherein the compound or the pharmacologically acceptable salt thereof is [(1R,5S,6S)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid benzenesulfonate.