CN109563133A - 多酰胺化合物及其用途 - Google Patents
多酰胺化合物及其用途 Download PDFInfo
- Publication number
- CN109563133A CN109563133A CN201780046820.6A CN201780046820A CN109563133A CN 109563133 A CN109563133 A CN 109563133A CN 201780046820 A CN201780046820 A CN 201780046820A CN 109563133 A CN109563133 A CN 109563133A
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- Prior art keywords
- amino
- compound
- group
- phenylpropionyl
- alkyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 353
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- 229940002612 prodrug Drugs 0.000 claims abstract description 62
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- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 claims abstract description 58
- 239000012453 solvate Substances 0.000 claims abstract description 57
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 103
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 92
- 150000003053 piperidines Chemical class 0.000 claims description 73
- 238000000034 method Methods 0.000 claims description 64
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 56
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- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 229910052736 halogen Inorganic materials 0.000 claims description 33
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
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- IUNXITMZUTWBJT-XEXPGFJZSA-N 4-amino-1-[(2R)-6-amino-2-[[(2R,4R,6R)-6-(3-aminopropylamino)-4-benzyl-2-(2-methylpropyl)-3,5-dioxo-7-phenylheptanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound NCCCN[C@@H](C(=O)[C@@H](C(=O)[C@H](C(=O)N[C@@H](C(=O)N1CCC(CC1)(C(=O)O)N)CCCCN)CC(C)C)CC1=CC=CC=C1)CC1=CC=CC=C1 IUNXITMZUTWBJT-XEXPGFJZSA-N 0.000 claims description 3
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- FIPPFBHCBUDBRR-UHFFFAOYSA-N henicosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCO FIPPFBHCBUDBRR-UHFFFAOYSA-N 0.000 claims description 3
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- ISLDWIKYMSYPPU-UHFFFAOYSA-N CCCCCCCCCCCCC.N1C=CC=CC=C1 Chemical compound CCCCCCCCCCCCC.N1C=CC=CC=C1 ISLDWIKYMSYPPU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
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- 238000001361 intraarterial administration Methods 0.000 claims description 2
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Abstract
本发明涉及多酰胺化合物及其用途，具体地，本发明涉及一类多酰胺化合物(其优选含有由相同或不同的L‑氨基酸或D‑氨基酸缩合形成的一个或多个酰胺键)、或其立体异构体、多晶型物、溶剂合物、或其代谢物、前药或药学上可接受的盐或酯、或其药物组合物，以及该类多酰胺化合物的制备方法及其在预防或治疗与κ阿片样物质受体相关的疾病中的用途。本发明的多酰胺化合物具有优异的κ阿片样物质受体激动效能、亲水能力和由此更小的穿透血脑屏障以及更低的进入脑部的能力。本发明的化合物对于κ阿片样物质受体更高的选择性、更低的成瘾性、改善的药物代谢动力学性质、改善的安全性(较低的毒性和/或较少的副作用、良好的患者顺应性，和/或较不易产生耐受性等更优异的成药性质。
Description
PCT国内申请，说明书已公开。
Claims (25)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2016108526048 | 2016-09-27 | ||
| CN201610852604 | 2016-09-27 | ||
| PCT/CN2017/103027 WO2018059331A1 (zh) | 2016-09-27 | 2017-09-22 | 多酰胺化合物及其用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109563133A true CN109563133A (zh) | 2019-04-02 |
| CN109563133B CN109563133B (zh) | 2020-09-11 |
Family
ID=61762536
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780046820.6A Active CN109563133B (zh) | 2016-09-27 | 2017-09-22 | 多酰胺化合物及其用途 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US11084847B2 (zh) |
| EP (1) | EP3521301B1 (zh) |
| JP (1) | JP6794602B2 (zh) |
| CN (1) | CN109563133B (zh) |
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| WO (1) | WO2018059331A1 (zh) |
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| CN113493490A (zh) * | 2020-04-03 | 2021-10-12 | 成都诺和晟泰生物科技有限公司 | 一种合成肽酰胺类化合物及其在医药领域的用途 |
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| CN111479800B (zh) * | 2018-02-12 | 2025-08-01 | 四川科伦博泰生物医药股份有限公司 | 一种中间体化合物及其制备方法，及以该中间体化合物制备多肽的固相合成方法 |
| CN111868070A (zh) * | 2018-05-15 | 2020-10-30 | 四川科伦博泰生物医药股份有限公司 | 一种多肽的纯化方法 |
| CN112469729A (zh) * | 2018-05-31 | 2021-03-09 | 悉尼大学 | 镇痛剂及其使用方法 |
| CN112739709B (zh) * | 2018-11-15 | 2025-05-02 | 四川科伦博泰生物医药股份有限公司 | 含有多肽类化合物的药物组合物及其制备方法和用途 |
| WO2021026492A1 (en) * | 2019-08-07 | 2021-02-11 | Humanwell Pharmaceutical US | Kappa opioid receptor peptide amide agonists |
| WO2021047470A1 (zh) * | 2019-09-10 | 2021-03-18 | 四川海思科制药有限公司 | 一种肽酰胺类化合物及其中间体的制备方法 |
| CN110790817A (zh) | 2019-11-12 | 2020-02-14 | 成都诺和晟泰生物科技有限公司 | 一种多肽类化合物、制剂、药物组合物及制备方法、应用 |
| EP4175944A4 (en) * | 2020-06-25 | 2024-03-06 | Humanwell Pharmaceutical US | PEPTIDES FOR THE TREATMENT OF MEDICAL DISORDERS |
| CN115873069A (zh) * | 2021-08-18 | 2023-03-31 | 天地恒一制药股份有限公司 | 肽酰胺类化合物、其药学上可接受的盐、立体异构体及其应用 |
| CN118891270A (zh) * | 2022-03-23 | 2024-11-01 | 江苏恩华药业股份有限公司 | 多酰胺类化合物、其制备方法及其医药用途 |
| EP4628082A1 (en) * | 2022-12-15 | 2025-10-08 | Yichang Humanwell Pharmaceutical Co., Ltd. | Pharmaceutical composition of kappa opioid receptor agonist, preparation method therefor, and use thereof |
| WO2025061122A1 (zh) * | 2023-09-22 | 2025-03-27 | 江苏恩华药业股份有限公司 | 一种多酰胺盐、其制备方法和应用 |
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- 2017-09-22 US US16/321,430 patent/US11084847B2/en active Active
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| CN113493490A (zh) * | 2020-04-03 | 2021-10-12 | 成都诺和晟泰生物科技有限公司 | 一种合成肽酰胺类化合物及其在医药领域的用途 |
| CN113493490B (zh) * | 2020-04-03 | 2024-03-12 | 成都诺和晟泰生物科技有限公司 | 一种合成肽酰胺类化合物及其在医药领域的用途 |
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| CN109563133B (zh) | 2020-09-11 |
| EP3521301A1 (en) | 2019-08-07 |
| US11084847B2 (en) | 2021-08-10 |
| JP6794602B2 (ja) | 2020-12-02 |
| JP2019526538A (ja) | 2019-09-19 |
| EP3521301B1 (en) | 2024-03-06 |
| US20200109166A1 (en) | 2020-04-09 |
| PH12019500199A1 (en) | 2019-10-21 |
| EP3521301A4 (en) | 2020-05-27 |
| WO2018059331A1 (zh) | 2018-04-05 |
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