当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Finding the perfect spot for fluorine: improving potency up to 40-fold during a rational fluorine scan of a Bruton's Tyrosine Kinase (BTK) inhibitor scaffold.

Finding the perfect spot for fluorine: improving potency up to 40-fold during a rational fluorine scan of a Bruton's Tyrosine Kinase (BTK) inhibitor scaffold.

Abstract：

:A rational fluorine scan based on co-crystal structures was explored to increase the potency of a series of selective BTK inhibitors. While fluorine substitution on a saturated bicyclic ring system yields no apparent benefit, the same operation on an unsaturated bicyclic ring can increase HWB activity by up to 40-fold. Comparison of co-crystal structures of parent molecules and fluorinated counterparts revealed the importance of placing fluorine at the optimal position to achieve favorable interactions with protein side chains.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Lou Y,Sweeney ZK,Kuglstatter A,Davis D,Goldstein DM,Han X,Hong J,Kocer B,Kondru RK,Litman R,McIntosh J,Sarma K,Suh J,Taygerly J,Owens TD

doi

10.1016/j.bmcl.2014.11.030

subject

Has Abstract

pub_date

2015-01-15 00:00:00

pages

367-71

issue

2

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)01214-1

journal_volume

25

pub_type

杂志文章

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