title: Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors.
abstract: Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice.
authors.affiliation: Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. Electronic address: ji.jiang@bms.com.
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Finlay
authors.affiliation: Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Lalgudi
authors.initials: L
authors.lastname: Harikrishnan
authors.affiliation: Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Muthoni
authors.initials: M
authors.lastname: Kamau
authors.affiliation: Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Tammy
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Adam
authors.affiliation: Department of Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: David
authors.initials: D
authors.lastname: Taylor
authors.affiliation: Department of Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Sleph
authors.affiliation: Department of Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Alice Ye A
authors.initials: AYA
authors.lastname: Chen
authors.affiliation: Department of Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Wexler
authors.affiliation: Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Salvati
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D053480:Cholesterol Ester Transfer Proteins
keywords: CETP inhibitors; HDL cholesterol; Hydroxyl 1,2-diphenylethanamine