Investigation of a Bicyclo[1.1.1]pentane as a Phenyl Replacement within an LpPLA2 Inhibitor.
ACS Med Chem Lett
; 8(1): 43-48, 2017 Jan 12.
Article
in En
| MEDLINE
| ID: mdl-28105273
ABSTRACT
We 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.
Full text:
1
Database:
MEDLINE
Language:
En
Journal:
ACS Med Chem Lett
Year:
2017
Type:
Article
Affiliation country:
United kingdom