The one-pot synthesis of butyl-1H-indol-3-alkylcarboxylic acid derivatives in ionic liquid as potent dual-acting agent for management of BPH
| Autor: | Zhenzhou Jiang, Baomin Xi, Fubiao Yang, Kaixuan Chen, Shuwen Liu, Yunong Zeng, Li-Yan Zeng |
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| Rok vydání: | 2020 |
| Předmět: |
Male
One-pot synthesis Carboxylic Acids Prostatic Hyperplasia Ionic Liquids Chemistry Techniques Synthetic 01 natural sciences Butyric acid 03 medical and health sciences chemistry.chemical_compound Drug Discovery Androgen Receptor Antagonists Humans Cytotoxicity Alkyl 030304 developmental biology Pharmacology chemistry.chemical_classification 0303 health sciences 010405 organic chemistry Organic Chemistry General Medicine Combinatorial chemistry 0104 chemical sciences Solvent chemistry Receptors Androgen Yield (chemistry) Ionic liquid Butyric Acid Linker |
| Zdroj: | European journal of medicinal chemistry. 205 |
| ISSN: | 1768-3254 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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