title: Synthesis and evaluation of aminophosphinic acid derivatives as inhibitors of renal dipeptidase.
abstract: Renal dipeptidase (RDP) is an enzyme overexpressed in benign and malignant colorectal tumors. In an effort to identify potent inhibitors of this enzyme, a series of aminophosphinic acid derivatives were synthesized. Compounds 3a and 3c in which the phenyl ring was para substituted with F and Br and olefin with Z geometry, showed better inhibitory activity against RDP enzyme (IC50 = 5-6 nM).
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA. ghallur1@jhmi.edu
authors.forename: Hallur
authors.initials: H
authors.lastname: Gurulingappa
authors.forename: Phillip
authors.initials: P
authors.lastname: Buckhalts
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Saeed R
authors.initials: SR
authors.lastname: Khan
mesh_terms: D000475:Alkenes / Q000737:chemistry / Q000494:pharmacology; D001965:Bromides / Q000737:chemistry / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000473:pathology; D004150:Dipeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005459:Fluorides / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000201:enzymology; D008956:Models, Chemical; D010721:Phosphinic Acids / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000475:Alkenes; D001965:Bromides; D004791:Enzyme Inhibitors; D010721:Phosphinic Acids; D004150:Dipeptidases; C038937:dipeptidase; D005459:Fluorides