title: Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain.
abstract: 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.
authors.affiliation: Beijing Institute of Pharmacology &amp; Toxicology, 27 Tai-Ping Road, Beijing 100850, China. swordsman_0526@163.com.
authors.forename: Haotian
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology &amp; Toxicology, 27 Tai-Ping Road, Beijing 100850, China. fsyn1996@163.com.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Fan
authors.affiliation: Beijing Institute of Pharmacology &amp; Toxicology, 27 Tai-Ping Road, Beijing 100850, China. chengjingchao3017@126.com.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Beijing Institute of Pharmacology &amp; Toxicology, 27 Tai-Ping Road, Beijing 100850, China. gundnir@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Pharmacology &amp; Toxicology, 27 Tai-Ping Road, Beijing 100850, China. bohuazhong@yahoo.com.
authors.forename: Bohua
authors.initials: B
authors.lastname: Zhong
authors.affiliation: Beijing Institute of Pharmacology &amp; Toxicology, 27 Tai-Ping Road, Beijing 100850, China. shiweiguo@bmi.ac.cn.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Shi
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D000700:Analgesics; D007211:Indoles; D062556:NAV1.7 Voltage-Gated Sodium Channel; D026941:Sodium Channel Blockers; C030374:indole
keywords: neuropathic pain; voltage-gated sodium channel blockers; α-aminoamide derivatives