JP7163906B2 - 末梢神経障害の治療剤又は予防剤 - Google Patents
末梢神経障害の治療剤又は予防剤 Download PDFInfo
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- JP7163906B2 JP7163906B2 JP2019510220A JP2019510220A JP7163906B2 JP 7163906 B2 JP7163906 B2 JP 7163906B2 JP 2019510220 A JP2019510220 A JP 2019510220A JP 2019510220 A JP2019510220 A JP 2019510220A JP 7163906 B2 JP7163906 B2 JP 7163906B2
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- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
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- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
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- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 1
- 229960004693 tenofovir disoproxil fumarate Drugs 0.000 description 1
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- 229960003433 thalidomide Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 229960001612 trastuzumab emtansine Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
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- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
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- 210000000689 upper leg Anatomy 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- NMDYYWFGPIMTKO-HBVLKOHWSA-N vinflunine Chemical compound C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@H]2C[C@@H](C(C)(F)F)CN1C2 NMDYYWFGPIMTKO-HBVLKOHWSA-N 0.000 description 1
- 229960000922 vinflunine Drugs 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
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- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
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- 229960002675 xylitol Drugs 0.000 description 1
- 235000020138 yakult Nutrition 0.000 description 1
- 229960000523 zalcitabine Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Hydrogenated Pyridines (AREA)
Description
[式中、*を付した炭素は不斉炭素であり、Aは、一般式(IIa)、(IIb)又は(IIc)で示される基を表し、
[式中、
*を付した炭素は不斉炭素であり、Aは、一般式(IIa)、(IIb)又は(IIc)で示される基を表し、
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ラット後根神経節由来株化神経細胞における細胞傷害に対する保護効果を検討した。
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ラット後根神経節由来株化神経細胞における細胞傷害に対する修復効果を検討した。
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ラット後根神経節細胞・シュワン細胞共培養の髄鞘形成に対する促進効果を検討した。
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ラット後根神経節細胞・シュワン細胞共培養におけるMBPの発現量に対する効果を検討した。
オキサリプラチンの投与によって発症する冷的アロディニア及び機械的アロディニアに対する環状アミン誘導体(I)又はその薬理学的に許容される塩の効果を検討した。
シスプラチンの投与によって発症する機械的アロディニアに対する環状アミン誘導体(I)又はその薬理学的に許容される塩の効果を検討した。
パクリタキセルの投与によって発症する機械的アロディニアに対する環状アミン誘導体(I)又はその薬理学的に許容される塩の効果を検討した。
ボルテゾミブの投与によって発症する機械的アロディニアに対する環状アミン誘導体(I)又はその薬理学的に許容される塩の治療効果を検討した。
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ラットEANモデルに対する抑制効果を検討した。
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ラットEANモデルの機械的アロディニアに対する抑制効果を検討した。
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ラットストレプトゾトシン誘発糖尿病モデルの機械的アロディニアに対する抑制効果を検討した。
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ラットストレプトゾトシン誘発糖尿病モデルの機械的アロディニアに対する抑制効果を検討した。
Claims (28)
- Aは、一般式(IIa)で示される基である、請求項1記載の治療剤。
- Aは、一般式(IIb)又は(IIc)で示される基である、請求項1記載の治療剤。
- Aは、一般式(IIa)で示される基であり、*を付した不斉炭素の立体化学が、S配置である、請求項1記載の治療剤。
- R1は、フッ素原子で置換されていてもよい、メチル基又はエチル基である、請求項1~4のいずれか一項記載の治療剤。
- R1は、メチル基、エチル基、ジフルオロメチル基又は2,2,2-トリフルオロエチル基である、請求項1~4のいずれか一項記載の治療剤。
- 末梢神経障害が薬剤性末梢神経障害である、請求項1~6のいずれか一項記載の一般式(I)で示される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、末梢神経障害の治療剤。
- 薬剤性末梢神経障害は、抗がん剤による末梢神経障害、抗ウイルス薬による末梢神経障害、抗菌薬による末梢神経障害、抗結核薬による末梢神経障害、抗不整脈薬による末梢神経障害、高脂血症治療薬による末梢神経障害、免疫抑制薬による末梢神経障害、痛風治療薬による末梢神経障害、抗てんかん薬による末梢神経障害、麻酔薬による末梢神経障害、ビタミン剤による末梢神経障害、抗酒癖薬による末梢神経障害及び降圧薬による末梢神経障害から選択される少なくとも1種である、請求項7記載の治療剤。
- 末梢神経障害が自己免疫性末梢神経障害である、請求項1~6のいずれか一項記載の一般式(I)で示される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、末梢神経障害の治療剤。
- 自己免疫性末梢神経障害は、ギラン・バレー症候群、慢性炎症性脱髄性多発根神経炎、多巣性運動神経障害及び異常タンパク血症に伴う神経障害から選択される少なくとも1種である、請求項9記載の治療剤。
- 末梢神経障害が代謝性末梢神経障害である、請求項1~6のいずれか一項記載の一般式(I)で示される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、末梢神経障害の治療剤。
- 代謝性末梢神経障害は、糖尿病性末梢神経障害、***性末梢神経障害、膠原病性末梢神経障害及びビタミン欠乏性末梢神経障害から選択される少なくとも1種である、請求項11記載の治療剤。
- 末梢神経障害が遺伝性末梢神経障害である、請求項1~6のいずれか一項記載の一般式(I)で示される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、末梢神経障害の治療剤。
- 遺伝性末梢神経障害は、シャルコー・マリー・トゥース病、家族性アミロイド・ポリニューロパチー、遺伝性圧脆弱性ニューロパチー及び遺伝性神経痛性筋肉萎縮症から選択される少なくとも1種である、請求項13記載の治療剤。
- Aは、一般式(IIa)で示される基である、請求項15記載の予防剤。
- Aは、一般式(IIb)又は(IIc)で示される基である、請求項15記載の予防剤。
- Aは、一般式(IIa)で示される基であり、*を付した不斉炭素の立体化学が、S配置である、請求項15記載の予防剤。
- R 1 は、フッ素原子で置換されていてもよい、メチル基又はエチル基である、請求項15~18のいずれか一項記載の予防剤。
- R 1 は、メチル基、エチル基、ジフルオロメチル基又は2,2,2-トリフルオロエチル基である、請求項15~18のいずれか一項記載の予防剤。
- 末梢神経障害が薬剤性末梢神経障害である、請求項15~20のいずれか一項記載の一般式(I)で示される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、末梢神経障害の予防剤。
- 薬剤性末梢神経障害は、抗がん剤による末梢神経障害、抗ウイルス薬による末梢神経障害、抗菌薬による末梢神経障害、抗結核薬による末梢神経障害、抗不整脈薬による末梢神経障害、高脂血症治療薬による末梢神経障害、免疫抑制薬による末梢神経障害、痛風治療薬による末梢神経障害、抗てんかん薬による末梢神経障害、麻酔薬による末梢神経障害、ビタミン剤による末梢神経障害、抗酒癖薬による末梢神経障害及び降圧薬による末梢神経障害から選択される少なくとも1種である、請求項21記載の予防剤。
- 末梢神経障害が自己免疫性末梢神経障害である、請求項15~20のいずれか一項記載の一般式(I)で示される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、末梢神経障害の予防剤。
- 自己免疫性末梢神経障害は、ギラン・バレー症候群、慢性炎症性脱髄性多発根神経炎、多巣性運動神経障害及び異常タンパク血症に伴う神経障害から選択される少なくとも1種である、請求項23記載の予防剤。
- 末梢神経障害が代謝性末梢神経障害である、請求項15~20のいずれか一項記載の一般式(I)で示される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、末梢神経障害の予防剤。
- 代謝性末梢神経障害は、糖尿病性末梢神経障害、***性末梢神経障害、膠原病性末梢神経障害及びビタミン欠乏性末梢神経障害から選択される少なくとも1種である、請求項25記載の予防剤。
- 末梢神経障害が遺伝性末梢神経障害である、請求項15~20のいずれか一項記載の一般式(I)で示される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、末梢神経障害の予防剤。
- 遺伝性末梢神経障害は、シャルコー・マリー・トゥース病、家族性アミロイド・ポリニューロパチー、遺伝性圧脆弱性ニューロパチー及び遺伝性神経痛性筋肉萎縮症から選択される少なくとも1種である、請求項27記載の予防剤。
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