Highly potent aminopyridines as Syk kinase inhibitors

被引：21

作者：

Castillo, Marcos ^{[2
]}

Forns, Pilar ^{[2
]}

Erra, Montse ^{[1
]}

Mir, Marta ^{[1
]}

Lopez, Manel ^{[1
]}

Maldonado, Monica ^{[1
]}

Orellana, Adelina ^{[1
]}

Carreno, Cristina ^{[1
]}

Ramis, Isabel ^{[1
]}

Miralpeix, Montserrat ^{[1
]}

Vidal, Bernat ^{[1
]}

机构：

[1] Almirall, Almirall Res Ctr, Barcelona 08980, Spain

[2] Almirall Barcelona Sci Pk Unit, Barcelona 08028, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 17期

关键词：

Syk kinase; Human mast cell line LAD2; Aminopyridines; TYROSINE KINASE; BIOLOGY;

D O I：

10.1016/j.bmcl.2012.07.045

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of potent Syk inhibitors has been developed from rational design. Highly potent aminopyridine derivatives bearing a 4-trifluoromethyl-2-pyridyl motif and represented by compound 13b IC50: 0.6 nM were identified. Substitution by a 2-pyrazinyl motif and SAR expansion in position 4 of the central core provided diverse potent non-cytotoxic Syk inhibitors showing nanomolar activity inhibiting human mast cell line LAD2 degranulation. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：5419 / 5423

页数：5

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