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Discovery of imidazo[1,2-b]pyridazines as IKKβ inhibitors. Part 2: improvement of potency in vitro and in vivo.

Abstract：

:We have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKKβ inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKKβ by the introduction of additional substituents based on the hypothesis derived from an interaction model study. These improved compounds showed inhibitory activity of TNFα production in mice.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Shimizu H,Yasumatsu I,Hamada T,Yoneda Y,Yamasaki T,Tanaka S,Toki T,Yokoyama M,Morishita K,Iimura S

doi

10.1016/j.bmcl.2010.12.078

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

904-8

issue

3

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)01842-1

journal_volume

21

pub_type

杂志文章

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