title: Aryl hetaryl ketones and thioketones as efficient inhibitors of peptidyl-prolyl cis-trans isomerases.
abstract: A series of 18 differently substituted new aryl hetaryl ketones and thioketones were synthesized in four to six steps from commercial starting materials. The new ketones were evaluated as inhibitors of the peptidyl-prolyl cis-trans isomerase hPin1 with K(i)  values ranging in the one-digit micromolar to sub-micromolar numbers. A crystal structure revealed the non-planar arrangement of the aryl residues at the carbonyl compound and supports the hypothesis that the new compounds might mimic the transition state of the enzymatic conversion.
authors.affiliation: Institut für Organische und Makromolekulare Chemie, Universität Düsseldorf, Universitätsstrasse 1, DE-40225 Düsseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hediger
authors.forename: Walter
authors.initials: W
authors.lastname: Frank
authors.forename: Michael
authors.initials: M
authors.lastname: Schumann
authors.forename: Gunter
authors.initials: G
authors.lastname: Fischer
authors.forename: Manfred
authors.initials: M
authors.lastname: Braun
mesh_terms: D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007659:Ketones; D013438:Sulfhydryl Compounds; D019696:Peptidylprolyl Isomerase