title: (3R,4S)-4-(2,4,5-Trifluorophenyl)-pyrrolidin-3-ylamine inhibitors of dipeptidyl peptidase IV: synthesis, in vitro, in vivo, and X-ray crystallographic characterization.
abstract: A series of pyrrolidine based inhibitors of dipeptidyl peptidase IV were developed from a high throughput screening hit for the treatment of type 2 diabetes. Potency, selectivity, and pharmacokinetic properties were optimized resulting in the identification of a pre-clinical candidate for further profiling.
authors.affiliation: Pfizer Global Research and Development, Cardiovascular and Metabolic Diseases, MS 8220-3141, Eastern Point Road, Groton, CT 06340, USA.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wright
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ammirati
authors.forename: Kim M
authors.initials: KM
authors.lastname: Andrews
authors.forename: Anne M
authors.initials: AM
authors.lastname: Brodeur
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Danley
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Doran
authors.forename: Jay S
authors.initials: JS
authors.lastname: Lillquist
authors.forename: Shenping
authors.initials: S
authors.lastname: Liu
authors.forename: Lester D
authors.initials: LD
authors.lastname: McClure
authors.forename: R Kirk
authors.initials: RK
authors.lastname: McPherson
authors.forename: Thanh V
authors.initials: TV
authors.lastname: Olson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Orena
authors.forename: Janice C
authors.initials: JC
authors.lastname: Parker
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Rocke
authors.forename: Walter C
authors.initials: WC
authors.lastname: Soeller
authors.forename: Carolyn B
authors.initials: CB
authors.lastname: Soglia
authors.forename: Judith L
authors.initials: JL
authors.lastname: Treadway
authors.forename: Maria A
authors.initials: MA
authors.lastname: Vanvolkenburg
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Eric D
authors.initials: ED
authors.lastname: Cox
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004285:Dogs; D005461:Fluorine / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism