title: Seco-prolinenitrile inhibitors of dipeptidyl peptidase IV define minimal pharmacophore requirements at P1.
abstract: A series of seco-prolinenitrile-containing dipeptides were synthesized and assayed as inhibitors of the N-terminal sequence-specific serine protease dipeptidyl peptidase IV, a promising new target for treatment of type 2 diabetes. The inhibitors described herein assess the minimum structural requirements at P1 for this enzyme, resulting in the identification of inhibitors with low nM potency.
authors.affiliation: Department of Discovery Chemistry, Bristol-Myers Squibb, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Magnin
authors.forename: Prakash C
authors.initials: PC
authors.lastname: Taunk
authors.forename: James G
authors.initials: JG
authors.lastname: Robertson
authors.forename: Aiying
authors.initials: A
authors.lastname: Wang
authors.forename: Jovita
authors.initials: J
authors.lastname: Marcinkeviciene
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kirby
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hamann
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry*; D000814:Aniline Compounds / Q000378:metabolism; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011392:Proline / Q000737:chemistry*
chemical_list: D000814:Aniline Compounds; D004151:Dipeptides; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D009570:Nitriles; C008625:nitroaniline; D011392:Proline; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase