title: Fluoro-olefins as peptidomimetic inhibitors of dipeptidyl peptidases.
abstract: The feasibility of the fluoro-olefin function as a peptidomimetic group in inhibitors for dipeptidyl peptidase IV and II (DPP IV and DPP II) is investigated by evaluation of N-substituted Gly-Psi[CF=C]pyrrolidines, Gly-Psi[CF=C]piperidines, and Gly-Psi[CF=C](2-cyano)pyrrolidines. Of this later class, the (Z)- and (E)-fluoro-olefin analogues were prepared and chemical stability in comparison with the parent amide was checked. Most of these compounds exhibited a strong binding preference toward DPP II with IC(50) values in the low micromolar range, while only low DPP IV inhibitory potential is seen.
authors.affiliation: Department of Medicinal Chemistry and Medical Biochemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Van der Veken
authors.forename: Kristel
authors.initials: K
authors.lastname: Senten
authors.forename: István
authors.initials: I
authors.lastname: Kertèsz
authors.forename: Ingrid
authors.initials: I
authors.lastname: De Meester
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lambeir
authors.forename: Marie-Berthe
authors.initials: MB
authors.lastname: Maes
authors.forename: Simon
authors.initials: S
authors.lastname: Scharpé
authors.forename: Achiel
authors.initials: A
authors.lastname: Haemers
authors.forename: Koen
authors.initials: K
authors.lastname: Augustyns
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004355:Drug Stability; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000475:Alkenes; D009570:Nitriles; D010455:Peptides; D010880:Piperidines; D011480:Protease Inhibitors; D011759:Pyrrolidines; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100151:dipeptidyl peptidase II; D018819:Dipeptidyl Peptidase 4