Fluoro-olefins as peptidomimetic inhibitors of dipeptidyl peptidases.
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.
Van der Veken
Pieter
P
Department of Medicinal Chemistry and Medical Biochemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
Senten
Kristel
K
Kertèsz
István
I
De Meester
Ingrid
I
Lambeir
Anne-Marie
AM
Maes
Marie-Berthe
MB
Scharpé
Simon
S
Haemers
Achiel
A
Augustyns
Koen
K
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
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