Design and synthesis of novel 2,3-dihydro-1H-isoindoles with high affinity and selectivity for the dopamine D3 receptor

被引：21

作者：

Austin, NE ^{[1
]}

Avenell, KY ^{[1
]}

Boyfield, I ^{[1
]}

Branch, CL ^{[1
]}

Hadley, MS ^{[1
]}

Jeffrey, P ^{[1
]}

Johnson, CN ^{[1
]}

Macdonald, GJ ^{[1
]}

Nash, DJ ^{[1
]}

Riley, GJ ^{[1
]}

Smith, AB ^{[1
]}

Stemp, G ^{[1
]}

Thewlis, KM ^{[1
]}

Vong, AKK ^{[1
]}

Wood, MD ^{[1
]}

机构：

[1] SmithKline Beecham Pharmaceut, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 05期

关键词：

D O I：

10.1016/S0960-894X(01)00037-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from the tetrahydroisoquinoline SB-277011 1, a novel series of 5-substituted-2,3-dihydro-1H-isoindoles has been designed. Subsequent optimisation resulted in identification of 19, which has high affinity for the dopamine D-3 receptor (pK(i) 8.3) and greater than or equal to 100-fold selectivity over other aminergic receptors. In rat studies 19 was brain penetrant with an excellent pharmacokinetic profile (oral bioavailability 77%, t(1/2) 5.2 h). (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：685 / 688

页数：4

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