title: Discovery of potent, selective, and orally bioavailable pyridone-based dipeptidyl peptidase-4 inhibitors.
abstract: anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9. The optimized compound exhibited good pharmacokinetic profiles in three preclinical species.
authors.affiliation: Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. Jinyou_Xu@merck.com
authors.forename: Jinyou
authors.initials: J
authors.lastname: Xu
authors.forename: Lan
authors.initials: L
authors.lastname: Wei
authors.forename: Robert
authors.initials: R
authors.lastname: Mathvink
authors.forename: Scott D
authors.initials: SD
authors.lastname: Edmondson
authors.forename: Anthony
authors.initials: A
authors.lastname: Mastracchio
authors.forename: George J
authors.initials: GJ
authors.lastname: Eiermann
authors.forename: Huaibing
authors.initials: H
authors.lastname: He
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Leone
authors.forename: Barbara
authors.initials: B
authors.lastname: Leiting
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lyons
authors.forename: Frank
authors.initials: F
authors.lastname: Marsilio
authors.forename: Reshma A
authors.initials: RA
authors.lastname: Patel
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Petrov
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wu
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: Ann E
authors.initials: AE
authors.lastname: Weber
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000284:Administration, Oral; D000577:Amides / Q000737:chemistry; D000818:Animals; D001682:Biological Availability; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004285:Dogs; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008253:Macaca mulatta; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011728:Pyridones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000577:Amides; D006023:Glycoproteins; D011480:Protease Inhibitors; D011728:Pyridones; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase; D009584:Nitrogen