title: 2-Aryl-2,2-difluoroacetamide FKBP12 ligands: synthesis and X-ray structural studies.
abstract: [structure: see text] 2-Aryl-2,2-difluoroacetamido-proline and pipecolate esters are high affinity FKBP12 ligands whose rotamase inhibitory activity is comparable to that seen for the corresponding ketoamides. X-ray structural studies suggest that the fluorine atoms participate in discrete interactions with the Phe36 phenyl ring and the Tyr26 hydroxyl group, with the latter resembling a moderate-to-weak hydrogen bond.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 5100, Wallingford, Connecticut 06492-7660, USA. gene.dubowchik@bms.com
authors.forename: G M
authors.initials: GM
authors.lastname: Dubowchik
authors.forename: V M
authors.initials: VM
authors.lastname: Vrudhula
authors.forename: B
authors.initials: B
authors.lastname: Dasgupta
authors.forename: J
authors.initials: J
authors.lastname: Ditta
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Sheriff
authors.forename: K
authors.initials: K
authors.lastname: Sipman
authors.forename: M
authors.initials: M
authors.lastname: Witmer
authors.forename: J
authors.initials: J
authors.lastname: Tredup
authors.forename: D M
authors.initials: DM
authors.lastname: Vyas
authors.forename: T A
authors.initials: TA
authors.lastname: Verdoorn
authors.forename: S
authors.initials: S
authors.lastname: Bollini
authors.forename: A
authors.initials: A
authors.lastname: Vinitsky
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D016559:Tacrolimus / Q000737:chemistry* / Q000378:metabolism; D022061:Tacrolimus Binding Protein 1A / Q000737:chemistry* / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000037:antagonists & inhibitors
chemical_list: D000081:Acetamides; D006845:Hydrocarbons, Fluorinated; D007166:Immunosuppressive Agents; D008024:Ligands; D022061:Tacrolimus Binding Protein 1A; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus