title: Structure-activity relationship study of 4-substituted piperidines at Leu26 moiety of novel p53-hDM2 inhibitors.
abstract: Led by the structural information of the screening hit with mDM2 protein, a structure modification of Leu26 moiety of the novel p53-hDM2 inhibitors was conducted. A structure-activity relationship study of 4-substituted piperidines revealed compound 20t with good potencies and excellent CYP450 profiles.
authors.affiliation: Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: yuan.tian2@merck.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Gibeau
authors.affiliation: Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Lahue
authors.affiliation: Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Shipps
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Corey
authors.initials: C
authors.lastname: Strickland
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Stéphane L
authors.initials: SL
authors.lastname: Bogen
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D007930:Leucine / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D010880:Piperidines; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D007930:Leucine
keywords: SAR; hDM2; p53