Imidazo[1,2-a]pyrimidines as functionally selective and orally bioavailable GABA-α2/α3 binding site agonists for the treatment of anxiety disorders

被引：132

作者：

Goodacre, SC

Street, LJ

Hallett, DJ

Crawforth, JM

Kelly, S

Owens, AP

Blackaby, WP

Lewis, RT

Stanley, J

Smith, AJ

Ferris, P

Sohal, B

Cook, SM

Pike, A

Brown, N

Wafford, KA

Marshall, G

Castro, JL

Atack, JR

机构：

[1] Merck Sharp & Dohme Res Labs, Ctr Res Neurosci, Dept Med Chem, Harlow CM20 2QR, Essex, England

[2] Merck Sharp & Dohme Res Labs, Ctr Res Neurosci, Dept Biochem, Harlow CM20 2QR, Essex, England

[3] Merck Sharp & Dohme Res Labs, Ctr Res Neurosci, Dept Pharmacol, Harlow CM20 2QR, Essex, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 01期

关键词：

D O I：

10.1021/jm051065l

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of high-affinity GABA(A) agonists with good oral bioavailability in rat and dog and functional selectivity for or the GABA(A)alpha 2 and -alpha 3 subtypes is reported. The 7-trifluoroinethylimidazopyrimidine 14g and the 7-propan-2-olimidazopyrimidine 14k are anxiolytic in both conditioned and unconditioned animal models of anxiety with minimal sedation observed at full BZ binding site occupancy.

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页码：35 / 38

页数：4

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