title: Stereoselective synthesis of cis-1,3-disubstituted cyclobutyl kinase inhibitors.
abstract: Two synthetic routes to a series of structurally novel kinase inhibitors containing a cis-1,3-disubstituted cyclobutane are described. The first route utilized addition of 3-aminocyclobutanol to 1,4-dinitroimidazole 5 as the crucial step in preparing 1, whereas the second route employed a novel 1,4-addition of 4-nitroimidazole 18 to in situ generated cyclobutenone 17 as the key reaction. This allowed for a stereoselective and shorter synthesis that eliminated the use of potentially explosive 1,4-dinitroimidazole 5. [structure: see text]
authors.affiliation: Neuroscience Medicinal Chemistry, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. chris_j_helal@groton.pfizer.com
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Helal
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Kang
authors.forename: John C
authors.initials: JC
authors.lastname: Lucas
authors.forename: Brooks R
authors.initials: BR
authors.lastname: Bohall
mesh_terms: D002073:Butanes / Q000737:chemistry*; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000737:chemistry; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
chemical_list: D002073:Butanes; D004791:Enzyme Inhibitors; D009593:Nitroimidazoles; C046888:butane; D010770:Phosphotransferases; C052587:4-nitroimidazole