title: Design and optimization of tricyclic gamma-secretase modulators.
abstract: Beginning with a diaminotriazine screening hit, several series of novel, tricyclic gamma-secretase modulators (GSMs) were designed. The SAR of several related series of GSMs is presented, and the in vivo profile of a lead molecule from the series is described.
authors: Discovery, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA. Electronic address: jianling.shi@bms.com.
authors: Jianliang
authors: J
authors: Shi
authors: Discovery, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors: Dmitry
authors: D
authors: Zuev
authors: Discovery, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors: Li
authors: L
authors: Xu
authors: Discovery, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors: Kimberley A
authors: KA
authors: Lentz
authors: Discovery, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors: James E
authors: JE
authors: Grace
authors: Discovery, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors: Jeremy H
authors: JH
authors: Toyn
authors: Discovery, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors: Richard E
authors: RE
authors: Olson
authors: Discovery, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors: John E
authors: JE
authors: Macor
authors: Discovery, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors: Lorin A
authors: LA
authors: Thompson
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000814:Aniline Compounds; D011480:Protease Inhibitors; D014227:Triazines; D053829:Amyloid Precursor Protein Secretases; C023650:aniline
keywords: Alzheimer’s disease; CYP3A4 inhibition; Gamma-secretase modulators