WO2016152952A1 - 環状アミン誘導体及びその医薬用途 - Google Patents
環状アミン誘導体及びその医薬用途 Download PDFInfo
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- WO2016152952A1 WO2016152952A1 PCT/JP2016/059293 JP2016059293W WO2016152952A1 WO 2016152952 A1 WO2016152952 A1 WO 2016152952A1 JP 2016059293 W JP2016059293 W JP 2016059293W WO 2016152952 A1 WO2016152952 A1 WO 2016152952A1
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- BERKYFKICZYNRP-UHFFFAOYSA-N CC(C)[n]1c(CCC(N(CCC2)CC2N(C)C)=O)ncc1 Chemical compound CC(C)[n]1c(CCC(N(CCC2)CC2N(C)C)=O)ncc1 BERKYFKICZYNRP-UHFFFAOYSA-N 0.000 description 1
- ULGFTWLGOJNKJJ-UHFFFAOYSA-N CN(C)C(CCC1)CN1C(CCc1ncc[n]1C)=O Chemical compound CN(C)C(CCC1)CN1C(CCc1ncc[n]1C)=O ULGFTWLGOJNKJJ-UHFFFAOYSA-N 0.000 description 1
- IRQWCOFOSMREBQ-UHFFFAOYSA-N CN(C)C1CNC1 Chemical compound CN(C)C1CNC1 IRQWCOFOSMREBQ-UHFFFAOYSA-N 0.000 description 1
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
Definitions
- Neuropathic pain is pathological pain caused by abnormal functioning of the peripheral or central nervous system itself, and is caused by direct damage or compression of nerve tissue even though nociceptors are not subjected to noxious stimulation. This refers to the pain that occurs.
- Anticonvulsants, antidepressants, anxiolytics or antiepileptics are used as therapeutic agents for neuropathic pain.
- n 1 and R 1 is unsubstituted, substituted with a fluorine atom, or substituted with a C 1 alkyloxy group.
- R 1 represents an alkyl group having 1 to 6 carbon atoms
- R 2 represents a hydrogen atom or a chlorine atom.
- n 3 and R 1 is unsubstituted, substituted with a fluorine atom, or substituted with an alkyloxy group having 1 to 4 carbon atoms.
- R 1 represents an alkyl group having 1 to 6 carbon atoms
- R 2 represents a hydrogen atom or a chlorine atom.
- the alkylation reaction is generally performed in a solvent.
- a solvent that does not inhibit the reaction is appropriately selected.
- examples of such a solvent include ethers such as tetrahydrofuran or 1,4-dioxane; amides such as N, N-dimethylformamide or N-methylpyrrolidone; or aliphatic nitriles such as acetonitrile or propionitrile. Can be mentioned. These mixed solvents may be used.
- the cyclic amine derivative (I) or a pharmacologically acceptable salt thereof can be used as a medicament because it has an excellent analgesic action, particularly a therapeutic effect for neuropathic pain, and is preferably used as an analgesic. It is preferably used as a therapeutic agent for neuropathic pain.
- the pharmaceutical containing the cyclic amine derivative (I) or a pharmaceutically acceptable salt thereof as an active ingredient is a mammal (eg, mouse, rat, hamster, rabbit, cat, dog, cow, sheep, monkey or human). In particular, when administered to humans, it exhibits excellent analgesic action, particularly therapeutic effect on neuropathic pain.
- disintegrant examples include starch and calcium carbonate.
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Abstract
Description
一般式(I)で示される環状アミン誘導体(以下、環状アミン誘導体(I)と略す;その他の一般式で示される誘導体についても同様に略す。)は、例えば、塩基存在下又は非存在下、3-ジメチルアミノ環状アミン誘導体(II)とカルボン酸誘導体(III)とを縮合剤を用いて縮合反応することにより得られる。
環状アミン誘導体(I)の薬理学的に許容される塩は、例えば、環状アミン誘導体(I)と酸とを混合することによる塩化反応により得られる。
(工程1)
3-ジメチルアミノ環状アミン誘導体(V)は、ケト環状アミン誘導体(IV)とジメチルアミンとの還元的アミノ化反応により得られる。
3-ジメチルアミノ環状アミン誘導体(V)は、3-アミノ環状アミン誘導体(VI)とホルムアルデヒドとの還元的アルキル化反応により得られる。
3-ジメチルアミノ環状アミン誘導体(II)は、3-ジメチルアミノ環状アミン誘導体(V)の脱保護により得られる。
(工程4)
2-ホルミルイミダゾール誘導体(VIII)は、2-ホルミルイミダゾール誘導体(VII)の塩基による脱プロトン化後にアルキル化試薬(LI)を作用させるアルキル化反応により得られる。
2-ホルミルイミダゾール誘導体(VIII)は、アルコール誘導体(IX)の酸化反応により得られる。
アクリル酸エステル誘導体(X)は、2-ホルミルイミダゾール誘導体(VIII)のオレフィン化反応により得られる。
エステル誘導体(XI)は、アクリル酸エステル誘導体(X)に対し、水素雰囲気下で遷移金属触媒を用いる還元反応により得られる。
カルボン酸誘導体(III)は、エステル誘導体(XI)の加水分解反応により得られる。
1H-NMR (400 MHz, CDCl3) δ: 1.48 (3H, d, J=6.4 Hz), 1.48 (3H, d, J=6.4 Hz), 5.48 (1H, quint, J=6.4 Hz), 7.30 (1H, s), 7.33 (1H, s), 9.83 (1H, s).
ESI-MS: m/z= 139 (M+H)+.
1H-NMR (400 MHz, DMSO) δ: 3.21 (3H, s), 3.61 (2H, d, J=5.2 Hz), 4.53 (2H, d, J=5.2 Hz), 7.27 (1H, s), 7.62 (1H, s), 9.69 (1H, s).
ESI-MS: m/z= 155 (M+H)+.
1H-NMR(400 MHz, CDCl3) δ:5.16 (2H, q, J=8.0 Hz), 7.25 (1H, brs), 7.38 (1H, brs), 9.83-9.85 (1H, m).
ESI-MS: m/z= 179 (M+H)+.
1H-NMR(400 MHz, CDCl3) δ: 3.97 (3H, s), 7.24 (1H, s), 9.70 (1H, s).
ESI-MS: m/z= 145 (M+H)+.
1H-NMR(400 MHz, CDCl3) δ: 3.76 (3H, s), 3.81 (3H, s), 6.82 (1H, d, J=15.6 Hz), 6.98 (1H, brs), 7.16 (1H, brs), 7.53 (1H, d, J=15.6Hz).
ESI-MS: m/z= 167 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ: 1.50 (3H, d, J=6.4 Hz), 1.50 (3H, d, J=6.4 Hz), 3.81 (3H, s), 4.62 (1H, quint, J=6.4 Hz), 6.87 (1H, d, J=15.6 Hz), 7.10 (1H, brs), 7.18 (1H, brs), 7.56 (1H, d, J=15.6 Hz).
ESI-MS: m/z= 195 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ: 3.82 (3H, s), 4.56-4.64 (2H, m), 6.93 (1H, d, J=15.2 Hz), 7.10 (1H, brs), 7.24 (1H, brs), 7.44 (1H, d, J=15.2 Hz).
ESI-MS: m/z= 235 (M+H)+.
1H-NMR(400 MHz, CDCl3) δ: 1.32 (3H, t, J=7.2 Hz), 3.32 (3H, s), 3.63 (2H, t, J=5.2 Hz), 4.20 (2H, t, J=5.2 Hz), 4.26 (2H, q, J=7.2 Hz), 6.84 (1H, d, J=15.4 Hz), 7.08 (1H, brs), 7.16 (1H, brs), 7.52 (1H, d, J=15.4 Hz).
ESI-MS: m/z= 225 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ: 3.67-3.69 (3H, m), 3.80-3.82 (3H, m), 6.78-6.85 (1H, m), 7.08-7.10 (1H, m), 7.44-7.50 (1H, m).
ESI-MS: m/z= 201 (M+H)+.
1H-NMR(400 MHz, CDCl3) δ: 2.84-2.96 (4H, m), 3.53 (3H, s), 3.70 (3H, s), 6.84 (1H, s).
ESI-MS: m/z= 203 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ: 2.16(6H, s), 2.62-2.68(2H, m), 2.92-2.98(2H, m), 3.02-3.09(1H, m), 3.60(3H, m), 3.78-3.85(1H, m), 3.93-4.02(2H, m), 4.11-4.17(1H, m), 6.78(1H, d, J=1.2Hz), 6.91(1H, d, J=1.2Hz).
ESI-MS: m/z= 237 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ:1.34-1.44(2H, m), 1.92-2.24(3H, m), 2.30(6H, s), 2.40-2.57(1H, m), 2.78-2.98(5H, m), 3.60(3H, s), 3.79-4.05(1H, m), 4.44-4.67(1H, m), 6.75-6.78(1H, m), 6.88-6.90(1H, m).
ESI-MS: m/z= 265 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ:1.34-1.44(2H, m), 1.92-2.24(3H, m), 2.30(6H, s), 2.40-2.57(1H, m), 2.78-2.98(5H, m), 3.60(3H, s), 3.79-4.05(1H, m), 4.44-4.67(1H, m), 6.75-6.78(1H, m), 6.88-6.90(1H, m).
ESI-MS: m/z= 265 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ:1.38-1.42(6H, m), 2.16(6H, s), 2.67-2.72(2H, m), 2.93-3.09(3H, m), 3.79-3.85(1H, m), 3.95-4.02(2H, m), 4.12-4.18(1H, m), 4.39-4.47(1H, m), 6.89-6.91(1H, m), 6.94-6.95(1H, m).
ESI-MS: m/z= 265 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ:1.39-1.44(6H, m), 1.68-1.83(3H, m), 1.98-2.60(9H, m), 2.80-3.05(5H, m), 3.84-4.09(1H, m), 4.40-4.71(2H, m), 6.89-6.96(2H, m).
ESI-MS: m/z= 293 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ: 1.39-1.44(6H, m), 1.68-1.83(3H, m), 1.98-2.60(9H, m), 2.80-3.05(5H, m), 3.84-4.09(1H, m), 4.40-4.71(2H, m), 6.89-6.96(2H, m).
ESI-MS: m/z= 293 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ:2.16(6H, s), 2.62-2.69(2H, m), 2.93-3.10(3H, m), 3.75-3.82(1H, m), 3.92-3.98(2H, m), 4.09-4.16(1H, m), 4.56-4.68(2H, m), 6.87-6.89(1H, m), 6.98-7.00(1H, m).
ESI-MS: m/z= 305 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ: 1.32-1.45(2H, m), 1.65-1.85(1H, m), 2.02-2.21(2H, m), 2.29-2.31(6H, m), 2.40-2.56(1H, m), 2.78-3.00(5H, m), 3.74-4.01(1H, m), 4.38-4.75(3H, m), 6.85-6.88(1H, m), 6.96-6.98(1H, m).
ESI-MS: m/z= 333 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ: 1.37-1.45(2H, m), 1.75-1.81(1H, m), 2.00-2.20(2H, m), 2.31-2.33(6H, m), 2.43-2.57(1H, m), 2.81-3.02(5H, m), 3.32 (3H, s), 3.59-3.62(2H, m), 3.84-4.11(3H, m), 4.49-4.69(1H, m), 6.89-6.93(2H, m).
ESI-MS: m/z= 309 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ:2.17 (6H, s), 2.56-2.69 (2H, m), 2.87-3.00 (2H, m), 3.03-3.09 (3H, m), 3.53 (3H, s), 3.81 (1H, dd, J=9.9, 5.2 Hz), 3.95-4.01 (2H, m), 4.13-4.17 (1H, m), 6.83(1H, s).
ESI-MS: m/z= 271 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ:1.30-1.48(2H, m), 1.68-1.84(1H, m), 1.92-2.22(2H, m), 2.28-2.31(6H, m), 2.40-2.58(1H, m), 2.77-3.00(5H, m), 3.51-3.54(3H, m), 3.75-4.02(1H, m), 4.42-4.64(1H, m), 6.80(1H, s).
ESI-MS: m/z= 299 (M+H)+.
1H-NMR (400 MHz, CDCl3) δ:1.30-1.48(2H, m), 1.68-1.84(1H, m), 1.92-2.22(2H, m), 2.28-2.31(6H, m), 2.40-2.58(1H, m), 2.77-3.00(5H, m), 3.51-3.54(3H, m), 3.75-4.02(1H, m), 4.42-4.64(1H, m), 6.80(1H, s).
ESI-MS: m/z= 299 (M+H)+.
1H-NMR (400 MHz, D2O) δ: 2.74-2.80(2H, m), 2.89(6H, s), 3.21-3.28(2H, m), 3.82(3H, s), 4.12-4.28(2H, m), 4.32-4.50(2H, m), 4.57-4.66(1H, m), 7.28-7.36(2H, m).
ESI-MS: 1-(3-(ジメチルアミノ)アゼチジン-1-イル)-3-(1-メチル-1H-イミダゾール-2-イル)-プロパン-1-オンとして: m/z= 237 (M+H)+.
1H-NMR (400 MHz, D2O) δ: 1.60-1.73(1H, m), 1.85-1.98(2H, m), 2.15-2.30(1H, m), 2.92-3.09(8H, m), 3.20-3.44(5H, m), 3.70-3.80(1H, m), 3.83(3H, s), 4.15-4.35(1H, m), 7.27-7.33(2H, m).
ESI-MS: (S)-1-(3-(ジメチルアミノ)ピペリジン-1-イル)-3-(1-メチル-1H-イミダゾール-2-イル)プロパン-1-オンとして: m/z= 265 (M+H)+.
1H-NMR (400 MHz, D2O) δ: 1.60-1.73(1H, m), 1.85-1.98(2H, m), 2.15-2.30(1H, m), 2.92-3.09(8H, m), 3.20-3.44(5H, m), 3.70-3.80(1H, m), 3.83(3H, s), 4.15-4.35(1H, m), 7.27-7.33(2H, m).
ESI-MS: (R)-1-(3-(ジメチルアミノ)ピペリジン-1-イル)-3-(1-メチル-1H-イミダゾール-2-イル)プロパン-1-オンとして: m/z= 265 (M+H)+.
1H-NMR (400 MHz, D2O) δ:1.47-1.51(6H, m), 2.74-2.80(2H, m), 2.88(6H, s), 3.24-3.30(2H, m), 4.13-4.24(2H, m), 4.33-4.48(2H, m), 4.58-4.74(2H, m), 7.36-7.38(1H, m), 7.49-7.51(1H, m).
ESI-MS: 1-(3-(ジメチルアミノ)アゼチジン-1-イル)-3-(1-イソプロピル-1H-イミダゾール-2-イル)プロパン-1-オンとして: m/z= 265 (M+H)+.
1H-NMR (400 MHz, D2O) δ:1.48-1.70(8H, m), 1.86-1.98(2H, m), 2.12-2.28(1H, m), 2.89-3.12(8H, m), 3.24-3.45(5H, m), 3.71-3.82(1H, m), 4.14-4.36(1H, m), 7.35(1H, brs), 7.50(1H, brs).
ESI-MS: (S)-1-(3-(ジメチルアミノ)ピペリジン-1-イル)-3-(1-イソプロピル-1H-イミダゾール-2-イル)プロパン-1-オンとして: m/z= 293 (M+H)+.
1H-NMR (400 MHz, D2O) δ: 1.48-1.70(8H, m), 1.86-1.98(2H, m), 2.12-2.28(1H, m), 2.89-3.12(8H, m), 3.24-3.45(5H, m), 3.71-3.82(1H, m), 4.14-4.36(1H, m), 7.35(1H, brs), 7.50(1H, brs).
ESI-MS: (R)-1-(3-(ジメチルアミノ)ピペリジン-1-イル)-3-(1-イソプロピル-1H-イミダゾール-2-イル)プロパン-1-オンとして: m/z= 293 (M+H)+.
1H-NMR (400 MHz, D2O) δ:2.77-2.84(2H, m), 2.89(6H, s), 3.27-3.33(2H, m), 4.13-4.26(2H, m), 4.32-4.47(2H, m), 4.57-4.64(1H, m), 5.08-5.16(2H, m), 7.42-7.46(1H, m), 7.51-7.55(1H, m).
ESI-MS: 1-(3-(ジメチルアミノ)アゼチジン-1-イル)-3-(1-(2,2,2-トリフルオロエチル)-1H-イミダゾール-2-イル)プロパン-1-オンとして: m/z= 305 (M+H)+.
1H-NMR (400 MHz, D2O) δ: 1.42-1.70(1H, m), 1.83-1.94(2H, m), 2.12-2.27(1H, m), 2.87-2.94(6H, m), 3.04-3.14(2H, m), 3.23-3.42(5H, m), 3.70-3.78(1H, m), 4.12-4.32(1H, m), 5.10-5.18(2H, m), 7.43-7.45(1H, m), 7.52-7.54(1H, m).
ESI-MS: (R)-1-(3-(ジメチルアミノ)ピペリジン-1-イル)-3-(1-(2,2,2-トリフルオロエチル)-1H-イミダゾール-2-イル)プロパン-1-オンとして: m/z= 333 (M+H)+.
1H-NMR (400 MHz, D2O) δ: 1.44-1.68(1H, m), 1.74-1.93(2H, m), 2.16-2.24(1H, m), 2.89-2.93(6H, m), 3.00-3.08(2H, m), 3.23-3.41(8H, m), 3.70-3.76(1H, m), 3.82-3.85(2H, m), 4.14-4.30(1H, m), 4.36-4.38(2H, m), 7.33-7.34(1H, m), 7.40-7.42(1H, m).
ESI-MS: (R)-1-(3-(ジメチルアミノ)ピペリジン-1-イル)-3-(1-(2-メトキシエチル)-1H-イミダゾール-2-イル)プロパン-1-オンとして: m/z= 309 (M+H)+.
1H-NMR (400 MHz, D2O) δ:2.78(2H, t, J=7.1 Hz), 2.92(6H, s), 3.26(2H, t, J= 7.1Hz), 3.77(3H, s), 4.17-4.28(2H, m), 4.37-4.41(1H, m), 4.45-4.48(1H, m), 4.61-4.66(1H, m), 7.44(1H, s).
ESI-MS: 3-(5-クロロ-1-メチル-1H-イミダゾール-2-イル)-1-(3-(ジメチルアミノ)アゼチジン-1-イル)プロパン-1-オンとして: m/z= 271 (M+H)+.
1H-NMR (400 MHz, D2O) δ: 1.60-1.71(1H, m), 1.78-1.96(2H, m), 2.14-2.28(1H, m), 2.89-2.96(6H, m), 3.01-3.10(2H, m), 3.23-3.44(5H, m), 3.70-3.80(4H, m), 4.20-4.33(1H, m), 7.43(1H, s).
ESI-MS: (S)-3-(5-クロロ-1-メチル-1H-イミダゾール-2-イル)-1-(3-(ジメチルアミノ)ピペリジン-1-イル)プロパン-1-オンとして: m/z= 299 (M+H)+.
1H-NMR (400 MHz, D2O) δ: 1.60-1.71(1H, m), 1.78-1.96(2H, m), 2.14-2.28(1H, m), 2.89-2.96(6H, m), 3.01-3.10(2H, m), 3.23-3.44(5H, m), 3.70-3.80(4H, m), 4.20-4.33(1H, m), 7.43(1H, s).
ESI-MS: (R)-3-(5-クロロ-1-メチル-1H-イミダゾール-2-イル)-1-(3-(ジメチルアミノ)ピペリジン-1-イル)プロパン-1-オンとして: m/z= 299 (M+H)+.
神経障害性疼痛を評価できるマウス坐骨神経部分結紮モデル(Seltzerモデル)を用い、環状アミン誘導体(I)又はその薬理学的に許容される塩の鎮痛作用を検討した。
マウス坐骨神経部分結紮モデルは、Seltzerらの方法(Malmbergら、Pain、1998年、第76巻、p.215-222)に従って作製した。
結果を図1~12に示す。図において、縦軸はvon Frey試験の総スコア(平均値±標準誤差;図1~12は、n=4~6である。)を示し、数値が高いほど痛みが強いことを示す。横軸には被験化合物投与後の時間(hr)を示す。薬効評価は、測定時間毎の「坐骨神経部分結紮+蒸留水」群(図中の「坐骨神経部分結紮+蒸留水」)を対照として、多群の対応のないt検定(Dunnettによる補正)(図1~3及び10~12)又は対応のない2群のt検定(図4~9)により統計処理を行った。図中の*印は、「坐骨神経部分結紮+蒸留水」群との比較で統計学的に有意である(p<0.05)ことを示す。
Claims (6)
- R2は、水素原子又は塩素原子である、請求項1記載の環状アミン誘導体又はその薬理学的に許容される塩。
- R1は、置換されていない炭素数1~6のアルキル基である、請求項2記載の環状アミン誘導体又はその薬理学的に許容される塩。
- 請求項1~3のいずれか一項記載の環状アミン誘導体又はその薬理学的に許容される塩を有効成分として含有する、医薬。
- 請求項1~3のいずれか一項記載の環状アミン誘導体又はその薬理学的に許容される塩を有効成分として含有する、鎮痛薬。
- 請求項1~3のいずれか一項記載の環状アミン誘導体又はその薬理学的に許容される塩を有効成分として含有する、神経障害性疼痛治療薬。
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