Substituted piperidines as HDM2 inhibitors.
Novel small molecule HDM2 inhibitor, substituted piperidine, was identified. Initial SAR study indicated potential for several position optimizations. Additional potency enhancement was achieved by introducing a sidechain off the aromatic ring. DMPK study of one of the active compounds has shown a moderate oral PK and reasonable bioavailability.
Discovery and Preclinical Sciences, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, United States. Electronic address: yaoma1@yahoo.com.
Yao
Y
Ma
Discovery and Preclinical Sciences, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, United States.
Brian R
BR
Lahue
Discovery and Preclinical Sciences, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, United States.
Gerald W
GW
Shipps
Discovery and Preclinical Sciences, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, United States.
Jeseca
J
Brookes
Discovery and Preclinical Sciences, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, United States.
Yaolin
Y
Wang
D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D010880:Piperidines; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
Cancer; HDM2; MDM2; Oncology; Small molecule inhibitor; Substituted piperidine; p53