title: Diastereoselective synthesis and configuration-dependent activity of (3-substituted-cycloalkyl)glycine pyrrolidides and thiazolidides as dipeptidyl peptidase IV inhibitors.
abstract: A diastereoselective synthesis was used to prepare a series of (3-substituted-cyclopentyl and -cyclohexyl)glycine pyrrolidides and thiazolidides. The three chiral centers were generated in an unambiguous, stereochemically defined manner. Inhibitory activity was dependent on the configuration at each stereocenter and on the nature of the 3-substituent. In the cyclopentylglycine pyrrolidide series, high potency against dipeptidyl peptidase IV and good selectivity could be achieved.
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: Hong
authors.initials: H
authors.lastname: Dong
authors.forename: Rosemary M
authors.initials: RM
authors.lastname: Sisco
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 / Q000187:drug effects* / Q000378:metabolism*; D008968:Molecular Conformation; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D011480:Protease Inhibitors; D011759:Pyrrolidines; D013844:Thiazoles; D018819:Dipeptidyl Peptidase 4