Phenyl isoxazole voltage-gated sodium channel blockers: Structure and activity relationship

被引：13

作者：

Macsari, Istvan ^{[1
]}

Sandberg, Lars ^{[1
]}

Besidski, Yevgeni ^{[1
]}

Gravenfors, Ylva ^{[1
]}

Ginman, Tobias ^{[1
]}

Bylund, Johan ^{[2
]}

Bueters, Tjerk ^{[2
]}

Eriksson, Anders B. ^{[3
]}

Lund, Per-Eric ^{[3
]}

Venyike, Elisabet ^{[3
]}

Arvidsson, Per I. ^{[4
,5
,6
]}

机构：

[1] AstraZeneca R&D, Innovat Med, CNSP iMed Sci, Med Chem, SE-15185 Sodertalje, Sweden

[2] AstraZeneca R&D, Innovat Med, CNSP iMed Sci, DMPK, SE-15185 Sodertalje, Sweden

[3] AstraZeneca R&D, Innovat Med, CNSP iMed Sci, Neurosci, SE-15185 Sodertalje, Sweden

[4] AstraZeneca R&D, Innovat Med, CNSP iMed Project Management, SE-15185 Sodertalje, Sweden

[5] Uppsala Univ, Uppsala Biomed Ctr, Dept Med Chem, SE-75123 Uppsala, Sweden

[6] Univ KwaZulu Natal, Sch Pharm & Pharmacol, ZA-4001 Durban, South Africa

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 13期

关键词：

Sodium channel blockers; Na(V)1.7 blocker; Neuropathic pain; Phenyl isoxazoles; Voltage-gated channel; SCN9A; PAIN;

D O I：

10.1016/j.bmcl.2011.05.041

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Blocking of certain sodium channels is considered to be an attractive mechanism to treat chronic pain conditions. Phenyl isoxazole carbamate 1 was identified as a potent and selective Na(V)1.7 blocker. Structural analogues of 1, both carbamates, ureas and amides, were proven to be useful in establishing the structure-activity relationship and improving ADME related properties. Amide 24 showed a good overall in vitro profile, that translated well to rat in vivo PK. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：3871 / 3876

页数：6

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