1402883-82-2

Upstream product

• 1537901-90-8 C₁₁H₈BrO₄^(1-)*Na⁽¹⁺⁾ 
• 31938-07-5 (3-bromophenyl)acetonitrile 
• 1402883-79-7 sodium (1R,2S)-1-(3-bromophenyl)-2-(hydroxymethyl)cyclopropanecarboxylate 
• 1402883-77-5 (1R,5S)-1-(3-bromophenyl)-3-oxabicyclo[3.1.0]hexan-2-one 

Downstream Products

• 1402883-85-5 (1R,2S)-1-(3-bromophenyl)-2-(3-ethoxy-3-oxopropanoyl)cyclopropanecarboxylic acid 
• 1402883-93-5 C₂₀H₂₂BrN₃O₅ 
• 1402883-99-1 2-bis(tert-butoxycarbonyl)amino-3-methyl-6-[(1S,2R)-2-(3-bromophenyl)cyclopropyl]pyrimidin-4(3H)-one 
• 1402883-41-3 2-amino-6-((1S,2R)-2-(3-bromophenyl)cyclopropyl)-3-methylpyrimidin-4(3H)-one 
• 1402883-42-4 2-amino-6-[(1S,2R)-2-(biphenyl-3-yl)-cyclopropyl]-3-methylpyrimidin-4(3H)-one hydrochloride 
• 1402883-43-5 2-amino-6-((1S,2R)-2-(3'-methoxybiphenyl-3-yl)cyclopropyl)-3-methylpyrimidin-4(3H)-one hydrochloride 
• 1402884-06-3 (1R,2S)-methyl 2-(2-amino-1-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-1-(3-bromophenyl)cyclopropanecarboxylate 
• 1402883-90-2 (1R,2S)-methyl 2-(2-(bis(tert-butoxycarbonyl)amino)-1-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-1-(3-bromophenyl)cyclopropanecarboxylate 
• 1402883-96-8 (1R,2S)-2-(2-(bis(tert-butoxycarbonyl)amino)-1-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-1-(3-bromophenyl)-cyclopropanecarboxylic acid 

Relevant academic research and scientific papers

CYCLOPROPANE DERIVATIVE HAVING BACE1 INHIBITING ACTIVITY

The present invention relates to compounds of the Formula (I) and (II): wherein each variable is as defined in the specification, pharmaceutically acceptable salts and solvates thereof, as well as use of such compounds as a BACE1 inhibitor. The compounds of the invention are useful as an agent for treating a disease induced by production, secretion and/or deposition of amyloid β protein.

Conformational restriction approach to β-Secretase (BACE1) inhibitors: Effect of a cyclopropane ring to induce an alternative binding mode

Improvement of a drugs binding activity using the conformational restriction approach with sp3 hybridized carbon is becoming a key strategy in drug discovery. We applied this approach to BACE1 inhibitors and designed four stereoisomeric cyclopropane compounds in which the ethylene linker of a known amidine-type inhibitor 2 was replaced with chiral cyclopropane rings. The synthesis and biologic evaluation of these compounds revealed that the cis-(1S,2R) isomer 6 exhibited the most potent BACE1 inhibitory activity among them. X-ray structure analysis of the complex of 6 and BACE1 revealed that its unique binding mode is due to the apparent CH-π interaction between the rigid cyclopropane ring and the Tyr71 side chain. A derivatization study using 6 as a lead molecule led to the development of highly potent inhibitors in which the structure-activity relationship as well as the binding mode of the compounds clearly differ from those of known amidine-type inhibitors.