title: Synthesis and structure-activity relationship of N-acyl-Gly-, N-acyl-Sar- and N-blocked-boroPro inhibitors of FAP, DPP4, and POP.
abstract: The structure-activity relationship of various N-acyl-Gly-, N-acyl-Sar-, and N-blocked-boroPro derivatives against three prolyl peptidases was explored. Several N-acyl-Gly- and N-blocked-boroPro compounds showed low nanomolar inhibitory activity against fibroblast activation protein (FAP) and prolyl oligopeptidase (POP) and selectivity against dipeptidyl peptidase-4 (DPP4). N-Acyl-Sar-boroPro analogs retained selectivity against DPP4 and potent POP inhibitory activity but displayed decreased FAP inhibitory activity.
authors.affiliation: Department of Medicinal Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Thuy
authors.initials: T
authors.lastname: Tran
authors.forename: Clifford
authors.initials: C
authors.lastname: Quan
authors.forename: Conrad Yap
authors.initials: CY
authors.lastname: Edosada
authors.forename: Mark
authors.initials: M
authors.lastname: Mayeda
authors.forename: Christian
authors.initials: C
authors.lastname: Wiesmann
authors.forename: Dan
authors.initials: D
authors.lastname: Sutherlin
authors.forename: Beni B
authors.initials: BB
authors.lastname: Wolf
mesh_terms: D058892:Adenosine Deaminase Inhibitors; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D010450:Endopeptidases; D018093:Gelatinases; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D011392:Proline / Q000737:chemistry* / Q000494:pharmacology; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D001896:Boron Compounds; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D010450:Endopeptidases; D018093:Gelatinases; D006023:Glycoproteins; D008565:Membrane Proteins; D011392:Proline; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors; D000099167:Fibroblast Activation Protein Alpha; C042807:DPP4 protein, human; C000705287:PREPL protein, human