Synthesis and evaluation of aminophosphinic acid derivatives as inhibitors of renal dipeptidase.
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).
Gurulingappa
Hallur
H
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA. ghallur1@jhmi.edu
Buckhalts
Phillip
P
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Khan
Saeed R
SR
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
D000475:Alkenes; D001965:Bromides; D004791:Enzyme Inhibitors; D010721:Phosphinic Acids; D004150:Dipeptidases; C038937:dipeptidase; D005459:Fluorides