Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain
The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of novel α-aminoamides containing an indole ring were designed and synthesized. These compounds were evaluated in mice using a formalin test and they exhibited significant anti...
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doaj-ece6e7e19a484f4fb2fc4c952c52f1ab2020-11-25T01:08:26ZengMDPI AGMolecules1420-30492016-06-0121779310.3390/molecules21070793molecules21070793Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic PainHaotian Li0Shiyong Fan1Jingchao Cheng2Ping Zhang3Bohua Zhong4Weiguo Shi5Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, ChinaBeijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, ChinaBeijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, ChinaBeijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, ChinaBeijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, ChinaBeijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, ChinaThe α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of novel α-aminoamides containing an indole ring were designed and synthesized. These compounds were evaluated in mice using a formalin test and they exhibited significant anti-allodynia activities. However, the analgesic mechanism of these compounds remains unclear; a subset of the synthesized compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp assay. Overall, these results suggest that introduction of an indole moiety to α-aminoamide derivatives can significantly improve their bioactivity and further study is warranted.http://www.mdpi.com/1420-3049/21/7/793neuropathic painα-aminoamide derivativesvoltage-gated sodium channel blockers |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Haotian Li Shiyong Fan Jingchao Cheng Ping Zhang Bohua Zhong Weiguo Shi |
spellingShingle |
Haotian Li Shiyong Fan Jingchao Cheng Ping Zhang Bohua Zhong Weiguo Shi Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain Molecules neuropathic pain α-aminoamide derivatives voltage-gated sodium channel blockers |
author_facet |
Haotian Li Shiyong Fan Jingchao Cheng Ping Zhang Bohua Zhong Weiguo Shi |
author_sort |
Haotian Li |
title |
Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain |
title_short |
Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain |
title_full |
Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain |
title_fullStr |
Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain |
title_full_unstemmed |
Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain |
title_sort |
synthesis and evaluation of novel α-aminoamides containing an indole moiety for the treatment of neuropathic pain |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2016-06-01 |
description |
The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of novel α-aminoamides containing an indole ring were designed and synthesized. These compounds were evaluated in mice using a formalin test and they exhibited significant anti-allodynia activities. However, the analgesic mechanism of these compounds remains unclear; a subset of the synthesized compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp assay. Overall, these results suggest that introduction of an indole moiety to α-aminoamide derivatives can significantly improve their bioactivity and further study is warranted. |
topic |
neuropathic pain α-aminoamide derivatives voltage-gated sodium channel blockers |
url |
http://www.mdpi.com/1420-3049/21/7/793 |
work_keys_str_mv |
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