title: Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7.
abstract: The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N-cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs.
authors.affiliation: ActivX Biosciences, Inc., 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.forename: Lifu
authors.initials: L
authors.lastname: Ma
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Wong
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.forename: Sergio
authors.initials: S
authors.lastname: Corral
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Yu
authors.forename: Tyzoon
authors.initials: T
authors.lastname: Nomanbhoy
authors.forename: Senaiet
authors.initials: S
authors.lastname: Alemayehu
authors.forename: Stacy R
authors.initials: SR
authors.lastname: Fuller
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Rosenblum
authors.forename: Natasha
authors.initials: N
authors.lastname: Rozenkrants
authors.forename: Lauro C
authors.initials: LC
authors.lastname: Minimo
authors.forename: William C
authors.initials: WC
authors.lastname: Ripka
authors.forename: Anna K
authors.initials: AK
authors.lastname: Szardenings
authors.forename: John W
authors.initials: JW
authors.lastname: Kozarich
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Shreder
mesh_terms: D058892:Adenosine Deaminase Inhibitors; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors; D001897:Boronic Acids; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D010450:Endopeptidases; D018093:Gelatinases; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D006801:Humans; D007155:Immunologic Factors / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D013329:Structure-Activity Relationship; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D001897:Boronic Acids; D004151:Dipeptides; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D018093:Gelatinases; D006023:Glycoproteins; D007155:Immunologic Factors; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C100151:dipeptidyl peptidase II; C042807:DPP4 protein, human