title: Potent and selective proline derived dipeptidyl peptidase IV inhibitors.
abstract: In-house screening of the Merck sample collection identified proline derived homophenylalanine 3 as a DPP-IV inhibitor with modest potency (DPP-IV IC50=1.9 microM). Optimization of 3 led to compound 37, which is among the most potent and selective DPP-IV inhibitors discovered to date.
authors.affiliation: Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 2000, Rahway, NJ 07065, USA. scott_edmondson@merck.com
authors.forename: Scott D
authors.initials: SD
authors.lastname: Edmondson
authors.forename: Anthony
authors.initials: A
authors.lastname: Mastracchio
authors.forename: Maria
authors.initials: M
authors.lastname: Beconi
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Colwell
authors.forename: Bahanu
authors.initials: B
authors.lastname: Habulihaz
authors.forename: Huaibing
authors.initials: H
authors.lastname: He
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Barbara
authors.initials: B
authors.lastname: Leiting
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: Ann
authors.initials: A
authors.lastname: Mao
authors.forename: Frank
authors.initials: F
authors.lastname: Marsilio
authors.forename: Reshma A
authors.initials: RA
authors.lastname: Patel
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wu
authors.forename: Lan
authors.initials: L
authors.lastname: Zhu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: Ann E
authors.initials: AE
authors.lastname: Weber
authors.forename: Emma R
authors.initials: ER
authors.lastname: Parmee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D011480:Protease Inhibitors; D011392:Proline; D018819:Dipeptidyl Peptidase 4