Refinement of histamine H3 ligands pharmacophore model leads to a new class of potent and selective naphthalene inverse agonists

被引：14

作者：

Roche, Olivier ^{[1
]}

Nettekoven, Matthias ^{[1
]}

Vifian, Walter ^{[1
]}

Sarmiento, Rosa Maria Rodriguez ^{[1
]}

机构：

[1] F Hoffmann La Roche Ltd, Pharmaceut Res Basel, Discovery Chem, CH-4070 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 15期

关键词：

histamine H(3) receptor; SAR; pharmacophore model; naphthalene; GPCR;

D O I：

10.1016/j.bmcl.2008.06.062

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The refinement of our original five point pharmacophore model for the H(3) receptor with the addition of a new acceptor feature is presented. The importance of this new acceptor feature for the binding and the selectivity against H(1), H(2) and H(4) has been validated using a newly synthesized naphthalene series. With the SAR deduced from several hundred naphthalene derivatives in various sub-classes the specific role of each pharmacophoric feature, by varying the geometry, size and charge of the molecules, was elucidated. This led to the discovery of a highly potent and selective new compounds series. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4377 / 4379

页数：3

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