Investigation of a Bicyclo[1.1.1]pentane as a Phenyl Replacement within an LpPLA<sub>2</sub> Inhibitor MeasomNicholas D. DownKenneth D. HirstDavid J. JamiesonCraig ManasEric S. PatelVipulkumar K. SomersDon O. 2016 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.