10.1021/acsmedchemlett.6b00281.s001
Nicholas
D. Measom
Nicholas
D.
Measom
Kenneth D. Down
Kenneth D.
Down
David J. Hirst
David J.
Hirst
Craig Jamieson
Craig
Jamieson
Eric S. Manas
Eric S.
Manas
Vipulkumar K. Patel
Vipulkumar K.
Patel
Don O. Somers
Don O.
Somers
Investigation of a Bicyclo[1.1.1]pentane as a Phenyl
Replacement within an LpPLA<sub>2</sub> Inhibitor
American Chemical Society
2016
bicyclo
moiety
physicochemical profile
data
investigation
LpPLA 2 Inhibitor
LpPLA 2 inhibitors
transformation
synthesis
Potency
bioisosteric phenyl replacements
incorporation
isostere
X-ray
dichlorocarbene insertion
target compounds
Bicyclo
Phenyl Replacement
bioisosteric counterparts
2016-11-15 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Investigation_of_a_Bicyclo_1_1_1_pentane_as_a_Phenyl_Replacement_within_an_LpPLA_sub_2_sub_Inhibitor/4263362
We describe the incorporation
of a bicyclo[1.1.1]pentane moiety
within two known LpPLA<sub>2</sub> inhibitors to act as bioisosteric
phenyl replacements. An efficient synthesis to the target compounds
was enabled with a dichlorocarbene insertion into a bicyclo[1.1.0]butane
system being the key transformation. Potency, physicochemical, and
X-ray crystallographic data were obtained to compare the known inhibitors
to their bioisosteric counterparts, which showed the isostere was
well tolerated and positively impacted on the physicochemical profile.