PMID- 32949920
OWN - NLM
STAT- MEDLINE
DCOM- 20210419
LR  - 20210419
IS  - 1768-3254 (Electronic)
IS  - 0223-5234 (Linking)
VI  - 205
DP  - 2020 Nov 1
TI  - The one-pot synthesis of butyl-1H-indol-3-alkylcarboxylic acid derivatives in 
      ionic liquid as potent dual-acting agent for management of BPH.
PG  - 112616
LID - S0223-5234(20)30588-2 [pii]
LID - 10.1016/j.ejmech.2020.112616 [doi]
AB  - Based on the SAR of both alpha(1)-AR antagonists and 5alpha-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 [C(6)min]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 
      alpha(1)-AR and 5alpha-reductase, and exhibited no obvious cytotoxicity against human 
      cells. The pharmacokinetic properties of 4aaa was also determined.
CI  - Copyright (c) 2020 Elsevier Masson SAS. All rights reserved.
FAU - Zeng, Li-Yan
AU  - Zeng LY
AD  - Guangdong Provincial Key Laboratory of New Drug Screening, School of 
      Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; 
      College of Chemistry and Chemical Engineering, Zhongkai University of Agriculture 
      and Engineering, Guangzhou, 510225, China.
FAU - Yang, Fubiao
AU  - Yang F
AD  - Guangdong Provincial Key Laboratory of New Drug Screening, School of 
      Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
FAU - Chen, Kaixuan
AU  - Chen K
AD  - Adlai Nortye Biopharma CO., LTD, Building 2, No. 452, No. 6 Street, Hangzhou 
      Economic and Technological Development Zone, Zhejiang Province, China.
FAU - Zeng, Yunong
AU  - Zeng Y
AD  - Guangdong Provincial Key Laboratory of New Drug Screening, School of 
      Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
FAU - Jiang, Zhenzhou
AU  - Jiang Z
AD  - New Drug Research and Development Center, China Pharmaceutical University, 
      Nanjing, 210009, China.
FAU - Liu, Shuwen
AU  - Liu S
AD  - Guangdong Provincial Key Laboratory of New Drug Screening, School of 
      Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. 
      Electronic address: liusw@smu.edu.cn.
FAU - Xi, Baomin
AU  - Xi B
AD  - Guangdong Provincial Key Laboratory of New Drug Screening, School of 
      Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. 
      Electronic address: xibaomin@smu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200719
PL  - France
TA  - Eur J Med Chem
JT  - European journal of medicinal chemistry
JID - 0420510
RN  - 0 (Androgen Receptor Antagonists)
RN  - 0 (Carboxylic Acids)
RN  - 0 (Ionic Liquids)
RN  - 0 (Receptors, Androgen)
RN  - 107-92-6 (Butyric Acid)
SB  - IM
MH  - Androgen Receptor Antagonists/chemical 
      synthesis/chemistry/pharmacology/therapeutic use
MH  - Butyric Acid/chemistry
MH  - Carboxylic Acids/*chemical synthesis/chemistry/*pharmacology/therapeutic use
MH  - Chemistry Techniques, Synthetic
MH  - Humans
MH  - Ionic Liquids/*chemistry
MH  - Male
MH  - Prostatic Hyperplasia/*drug therapy
MH  - Receptors, Androgen/metabolism
OTO - NOTNLM
OT  - 5alpha-reductase inhibitors
OT  - BPH
OT  - Dual-acting
OT  - Ionic liquids
OT  - alpha(1)-AR antagonists
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/09/20 06:00
MHDA- 2021/04/20 06:00
CRDT- 2020/09/19 20:14
PHST- 2020/02/01 00:00 [received]
PHST- 2020/06/21 00:00 [revised]
PHST- 2020/06/22 00:00 [accepted]
PHST- 2020/09/20 06:00 [pubmed]
PHST- 2021/04/20 06:00 [medline]
PHST- 2020/09/19 20:14 [entrez]
AID - S0223-5234(20)30588-2 [pii]
AID - 10.1016/j.ejmech.2020.112616 [doi]
PST - ppublish
SO  - Eur J Med Chem. 2020 Nov 1;205:112616. doi: 10.1016/j.ejmech.2020.112616. Epub 
      2020 Jul 19.