Synthesis and biological evaluation of 6-aryl-6H-pyrrolo[3,4-d]-pyridazine derivatives as high-affinity ligands of the α2δ subunit of voltage-gated calcium channels

被引：15

作者：

Hu, T

Stearns, BA

Campbell, BT

Arruda, JM

Chen, CX

Aiyar, J

Bezverkov, RE

Santini, A

Schaffhauser, H

Liu, WS

Venkatraman, S

Munoz, B

机构：

[1] Merck Res Labs, Dept Med Chem, San Diego, CA 92121 USA

[2] Merck Res Labs, Dept Neuropharmacol, San Diego, CA 92121 USA

[3] Merck Res Labs, Dept Drug Metab, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 09期

关键词：

gabapentin; affinity; SAR;

D O I：

10.1016/j.bmcl.2004.02.070

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of 2H-pyrrolo[3,4-c]pyridazine ligands of the alpha(2)delta subunit of voltage-gated calcium channels is described. Compound 4a with high affinity toward alpha(2)delta was identified through structure-activity relationship studies of the lead compound. Tritiated ligand [H-3]-4b was synthesized to demonstrate that this ligand binds to the same site as Gabapentin toward alpha(2)delta subunit of voltage-gated calcium channels. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：2031 / 2034

页数：4

共 10 条

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Bryans JS, 1999, MED RES REV, V19, P149, DOI 10.1002/(SICI)1098-1128(199903)19:2<149::AID-MED3>3.0.CO

[2]

2-B

[3] Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents [J].