870852-75-8

Upstream product

• 159294-99-2 1,2,3-trifluoro-5-vinylbenzene 
• 1367361-09-8 C₁₆H₁₄F₃NO₃ 
• 1213556-08-1 (S)-2-amino-2-(3,4,5-trifluorophenyl)ethanol 
• 1352130-00-7 (S,E)-5-chloro-N-(2-hydroxy-1-(3,4,5-trifluorophenyl)ethyl)-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)pentanamide 
• 1022990-86-8 (S)-2-amino-2-(3,4,5-trifluorophenyl)acetic acid 
• 138526-69-9 3,4,5-trifluoro-1-bromobenzene 
• 870843-26-8 tert-butyl 5-chloro-2-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}valerate 
• 870843-25-7 5-chloro-2-(diethoxyphosphoryl)valeric acid tert-butyl ester 
• 870837-18-6 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde 
• 870837-21-1 3-methoxy-4-(4-methylimidazol-1-yl)benzoic acid methyl ester 
• 870850-40-1 (E)-1-(4-(2-carboxy-5-chloropent-1-en-1-yl)-2-methoxyphenyl)-4-methyl-1H-imidazol-3-ium 2,2,2-trifluoroacetate 
• 870837-20-0 4-[formyl-(2-oxopropyl)amino]-3-methoxybenzoic acid methyl ester 
• 41608-64-4 methyl 3-methoxy-4-aminobenzoate 
• 5081-37-8 methyl 3-methoxy-4-nitrobenzoate 

Downstream Products

• 1352130-01-8 (S,E)-1-(2-(aminooxy)-1-(3,4,5-trifluorophenyl)ethyl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one 
• 1352130-02-9 (S,E)-9-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)-benzylidene)-4-(3,4,5-trifluorophenyl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]oxadiazine 

Relevant academic research and scientific papers

Synthesis of the γ-Secretase Modulator MK-8428

The synthesis of the γ-secretase modulator MK-8428 (1) is described. The synthesis is highlighted by an enzyme-catalyzed reaction to access 3,4,5-trifluoro-(S)-phenylglycine, a 1-pot activation/displacement/deprotection sequence to introduce the aminooxy functionality and a dehydrative intramolecular cyclization under mild conditions to form the oxadiazine heterocycle of 1. In situ reaction monitoring was employed to understand the deleterious role of water during the formation of a methanesulfonate ester in the 1-pot activation/displacement/deprotection sequence.

Cyclic hydroxyamidines as amide isosteres: Discovery of oxadiazolines and oxadiazines as potent and highly efficacious γ-secretase modulators in vivo

Cyclic hydroxyamidines were designed and validated as isosteric replacements of the amide functionality. Compounds with these structural motifs were found to be metabolically stable and to possess highly desirable pharmacokinetic profiles. These designs were applied in the identification of γ-secretase modulators leading to highly efficacious agents for reduction of central nervous system Aβ42 in various animal models.