The one-pot synthesis of butyl-1H-indol-3-alkylcarboxylic acid derivatives in ionic liquid as potent dual-acting agent for management of BPH
Copyright © 2020 Elsevier Masson SAS. All rights reserved..
Based on the SAR of both α1-AR antagonists and 5α-reductase (5AR) inhibitors, the dual-acting agent 4-(1-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-1H-indol-3-yl)butanoic acid 4aaa was designed against BPH and synthesized by two steps of N-alkylation. One-pot protocol towards 4aaa was newly developed. With IL [C6min]Br as solvent, the yield of 4aaa was increased to 75.1% from 16.0% and the reaction time was shortened in 1.5 h from 48 h. 25 derivatives structurally based on arylpiperazine and indolyl butyric acid with alkyl linker were prepared. The protocol was futher extended to get another 14 derivatives wherein O-alkylation was involved, and applied to the synthesis of biologically efficient molecules DPQ and Aripiprazole. Expectedly, compound 4aaa exhibited dual inhibition of α1-AR and 5α-reductase, and exhibited no obvious cytotoxicity against human cells. The pharmacokinetic properties of 4aaa was also determined.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:205 |
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| Enthalten in: |
European journal of medicinal chemistry - 205(2020) vom: 01. Nov., Seite 112616 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zeng, Li-Yan [VerfasserIn] |
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| Links: |
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| Themen: |
α(1)-AR antagonists |
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| Anmerkungen: |
Date Completed 19.04.2021 Date Revised 19.04.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2020.112616 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315212918 |
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| 245 | 1 | 4 | |a The one-pot synthesis of butyl-1H-indol-3-alkylcarboxylic acid derivatives in ionic liquid as potent dual-acting agent for management of BPH |
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| 500 | |a Date Completed 19.04.2021 | ||
| 500 | |a Date Revised 19.04.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Based on the SAR of both α1-AR antagonists and 5α-reductase (5AR) inhibitors, the dual-acting agent 4-(1-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-1H-indol-3-yl)butanoic acid 4aaa was designed against BPH and synthesized by two steps of N-alkylation. One-pot protocol towards 4aaa was newly developed. With IL [C6min]Br as solvent, the yield of 4aaa was increased to 75.1% from 16.0% and the reaction time was shortened in 1.5 h from 48 h. 25 derivatives structurally based on arylpiperazine and indolyl butyric acid with alkyl linker were prepared. The protocol was futher extended to get another 14 derivatives wherein O-alkylation was involved, and applied to the synthesis of biologically efficient molecules DPQ and Aripiprazole. Expectedly, compound 4aaa exhibited dual inhibition of α1-AR and 5α-reductase, and exhibited no obvious cytotoxicity against human cells. The pharmacokinetic properties of 4aaa was also determined | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 5α-reductase inhibitors | |
| 650 | 4 | |a BPH | |
| 650 | 4 | |a Dual-acting | |
| 650 | 4 | |a Ionic liquids | |
| 650 | 4 | |a α(1)-AR antagonists | |
| 650 | 7 | |a Androgen Receptor Antagonists |2 NLM | |
| 650 | 7 | |a Carboxylic Acids |2 NLM | |
| 650 | 7 | |a Ionic Liquids |2 NLM | |
| 650 | 7 | |a Receptors, Androgen |2 NLM | |
| 650 | 7 | |a Butyric Acid |2 NLM | |
| 650 | 7 | |a 107-92-6 |2 NLM | |
| 700 | 1 | |a Yang, Fubiao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Kaixuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Yunong |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Zhenzhou |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Shuwen |e verfasserin |4 aut | |
| 700 | 1 | |a Xi, Baomin |e verfasserin |4 aut | |
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