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：130
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.
引用
收藏
页码：35 / 38
页数：4
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