ml6b00281_si_001.pdf (314.13 kB)
Investigation of a Bicyclo[1.1.1]pentane as a Phenyl Replacement within an LpPLA2 Inhibitor
journal contribution
posted on 2016-11-15, 00:00 authored by Nicholas
D. Measom, Kenneth D. Down, David J. Hirst, Craig Jamieson, Eric S. Manas, Vipulkumar K. Patel, Don O. SomersWe describe the incorporation
of a bicyclo[1.1.1]pentane moiety
within two known LpPLA2 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.