title: Dipeptidyl peptidase IV inhibitors derived from beta-aminoacylpiperidines bearing a fused thiazole, oxazole, isoxazole, or pyrazole.
abstract: A series of beta-aminoacylpiperidines bearing various fused five-membered heterocyclic rings was synthesized as dipeptidyl peptidase IV inhibitors. Potent and relatively selective inhibition could be obtained, depending on choice of heterocycle, regioisomerism, and substitution. In particular, one analog (74, DPP-IV IC50=26 nM) exhibited good oral bioavailability and acceptable half-life in the rat, albeit with rather high clearance.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. wally_ashton@merck.com
authors.forename: Wallace T
authors.initials: WT
authors.lastname: Ashton
authors.forename: Rosemary M
authors.initials: RM
authors.lastname: Sisco
authors.forename: Hong
authors.initials: H
authors.lastname: Dong
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: Huaibing
authors.initials: H
authors.lastname: He
authors.forename: George A
authors.initials: GA
authors.lastname: Doss
authors.forename: Barbara
authors.initials: B
authors.lastname: Leiting
authors.forename: Reshma A
authors.initials: RA
authors.lastname: Patel
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wu
authors.forename: Frank
authors.initials: F
authors.lastname: Marsilio
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: Ann E
authors.initials: AE
authors.lastname: Weber
mesh_terms: D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D007555:Isoxazoles; D010080:Oxazoles; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles; D013844:Thiazoles
chemical_list: D007555:Isoxazoles; D010080:Oxazoles; D010880:Piperidines; D011480:Protease Inhibitors; D011720:Pyrazoles; D013844:Thiazoles; D018819:Dipeptidyl Peptidase 4