152911-75-6

Upstream product

• 630-19-3 pivalaldehyde 
• 152911-54-1 (+/-)-2-amino-5-chloro-α-(2,3-dimethoxyphenyl)benzyl alcohol 
• 177410-73-0 (+/-)-5-chloro-α-(2,3-dimethoxyphenyl)-2-pivaloylaminobenzyl alcohol 
• 106-47-8 4-chloro-aniline 
• 3282-30-2 pivaloyl chloride 
• 65854-91-3 N-(4-chlorophenyl)-2,2-dimethylpropionamide 
• 848611-30-3 2,3-dimethoxyphenylmagnesium bromide 
• 152911-43-8 (2-amino-5-chlorophenyl)(2,3-dimethoxyphenyl)methanone 
• 7033-50-3 6-chloro-2-methyl-4H-benzo[d][1,3]oxazin-4-one 
• 91-16-7 1,2-dimethoxybenzene 

Downstream Products

• 152911-97-2 (E)-3-[{4-Chloro-2-[(2,3-dimethoxy-phenyl)-hydroxy-methyl]-phenyl}-(2,2-dimethyl-propyl)-carbamoyl]-acrylic acid ethyl ester 
• 406684-81-9 methyl N-[(3S,5R)-7-chloro-5-(2,3-dimethoxyphenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetyl]-L-leucinate 
• 406684-80-8 methyl N-[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetyl]-L-leucinate 

Relevant academic research and scientific papers

Discovery of a new 2-aminobenzhydrol template for highly potent squalene synthase inhibitors

To obtain small and efficient squalene synthase inhibitors, a flexible 2-aminobenzhydrol open form structure was designed and showed potent inhibitory activity comparable to 4,1-benzoxazepin compounds. Further chemical modification led to the discovery of a novel template with a strong squalene synthase inhibitory activity, and its basic structure-activity relationship was revealed. The X-ray crystallographic data of compound 12 bound to the active site of squalene synthase provided an important insight into the binding mode of this alternative template that formed 11-membered ring conformations with an intramolecular hydrogen bond.

Novel 4,1-benzoxazepine derivatives with potent squalene synthase inhibitory activities

A series of (3,5-trans)-2-oxo-5-phenyl-1,2,3,5-tetrahydro-4,1-benzoxazepine derivatives were synthesized and evaluated for squalene synthase inhibitory and cholesterol biosynthesis inhibitory activities. Through modification of substituents of the lead compounds 1a and 1b, it was found that 4,1-benzoxazepine-3-acetic acid derivatives with isobutyl and neopentyl groups at the 1-position, the chloro atom at the 7-position, and the chloro and methoxy groups at the 2'-position on the 5-phenyl ring, had potent squalene synthase inhibitory activity. Among such compounds, the 5-(2,3-dimethoxyphenyl) derivative 2t exhibited potent inhibition of cholesterol biosynthesis in HepG2 cells. As a result of optical resolution study of 2t, the absolute stereochemistry required for inibitory activity was determined to be 3R,5S. In vivo study showed that the sodium salt of (3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-aceitc acid 20 effectively reduced plasma cholesterol in marmosets. Copyright