4489-17-2

Upstream product

• 50672-13-4 (±)-trans-2,2-dimethyl-3-phenylcyclopropanecarboxylic acid 
• 103-36-6 ethyl 3-phenyl-2-propenoate 
• 61751-36-8 (±)-trans-ethyl 2,2-dimethyl-3-phenylcyclopropanecarboxylate 
• 768-49-0 (2-methyl-1-propenyl)-benzene 

Downstream Products

• 96170-90-0 (+/-)(1Ξ)-2,2-dimethyl-3t-phenyl-cyclopropane-r-carboxylic acid-((Ξ)-3-allyl-2-methyl-4-oxo-cyclopent-2-enyl ester) 
• 91245-67-9 trans-3,3-dimethyl-2-phenylcyclopropanamine 
• 1557242-99-5 (4S)-4-benzyl-3-{[(1R,3R)-2,2-dimethyl-3-phenylcyclopropyl]carbonyl}-1,3-oxazolidin-2-one 
• 1557243-03-4 (4S)-4-benzyl-3-{[(1S,3S)-2,2-dimethyl-3-phenylcyclopropyl]carbonyl}-1,3-oxazolidin-2-one 
• 1557243-42-1 (1R,3R)-N-(5-chloro-2-methoxyphenyl)-2,2-dimethyl-3-phenylcyclopropane-1-carboxamide 
• 494846-57-0 (-)-trans-(1S,3S)-2,2-dimethyl-3-phenylcyclopropanecarboxylic acid 
• 494846-26-3 (+)-trans-(1R,3R)-2,2-dimethyl-3-phenylcyclopropanecarboxylic acid 
• 1557240-70-6 4-[(1S,3S)-3-({[4-fluoro-2-(trifluoromethyl)phenyl]amino}methyl)-2,2-dimethylcyclopropyl]benzenesulfonamide 
• 1557241-14-1 4-[(1S,3S)-3-{[(4,5-difluoro-2-methylphenyl)amino]methyl}-2,2-dimethylcyclopropyl]benzenesulfonamide 
• 1557241-08-3 4-[(1R,3R)-3-{[(4,5-difluoro-2-methylphenyl)amino]methyl}-2,2-dimethylcyclopropyl]benzenesulfonamide 
• 1557241-10-7 4-[(1S,3S)-3-{[(5-fluoro-2-methylphenyl)amino]methyl}-2,2-dimethylcyclopropyl]benzenesulfonamide 
• 1557241-04-9 4-[(1R,3R)-3-{[(5-fluoro-2-methylphenyl)amino]methyl}-2,2-dimethylcyclopropyl]benzenesulfonamide 
• 1557244-03-7 (1S,3S)-N-(4,5-difluoro-2-methylphenyl)-2,2-dimethyl-3-phenylcyclopropanecarboxamide 
• 1557244-05-9 (1S,3S)-N-(4,5-difluoro-2-methylphenyl)-2,2-dimethyl-3-(4-sulfamoylphenyl)cyclopropanecarboxamide 

Relevant academic research and scientific papers

Discovery of BNC375, a Potent, Selective, and Orally Available Type i Positive Allosteric Modulator of α7 nAChRs

Positive allosteric modulators (PAMs) of α7 nAChRs can have different properties with respect to their effects on channel kinetics. Type I PAMs amplify peak channel response to acetylcholine but do not appear to influence channel desensitization kinetics, whereas Type II PAMs both increase channel response and delay receptor desensitization. Both Type I and Type II PAMs are reported in literature, but there are limited reports describing their structure-kinetic profile relationships. Here, we report a novel class of compounds with either Type I or Type II behavior that can be tuned by the relative stereochemistry around the central cyclopropyl ring: for example, (R,R)-13 (BNC375) and its analogues with RR stereochemistry around the central cyclopropyl ring are Type I PAMs, whereas compounds in the same series with SS stereochemistry (e.g., (S,S)-13) are Type II PAMs as measured using patch-clamp electrophysiology. Further fine control over the kinetics has been achieved by changing the substitutions on the aniline ring: generally the substitution of aniline with strong electron withdrawing groups reduces the Type II character of these compounds. Our structure-activity optimization efforts have led to the discovery of BNC375, a small molecule with good CNS-drug like properties and clinical candidate potential.

α7 NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS AND USES THEREOF-I

The present invention relates to chemical compounds of formula (I), with the substituents as described in the specification, useful in the positive modulation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR). The invention also relates to the use of these compounds in the treatment or prevention of a broad range of diseases in which the positive modulation of α7 nAChR is advantageous, including neurodegenerative and neuropsychiatric diseases and also neuropathic pain and inflammatory diseases.