1557243-93-2

Upstream product

• 494846-26-3 (+)-trans-(1R,3R)-2,2-dimethyl-3-phenylcyclopropanecarboxylic acid 
• 1557242-99-5 (4S)-4-benzyl-3-{[(1R,3R)-2,2-dimethyl-3-phenylcyclopropyl]carbonyl}-1,3-oxazolidin-2-one 
• 367-29-3 3-fluoro-6-methylaniline 
• 1557243-89-6 (1R,3R)-N-(5-fluoro-2-methylphenyl)-2,2-dimethyl-3-phenylcyclopropanecarboxamide 
• 4489-17-2 (+/-)-2,2-dimethyl-3t-phenyl-cyclopropane-r-carbonyl chloride 
• 50672-13-4 (±)-trans-2,2-dimethyl-3-phenylcyclopropanecarboxylic acid 

Downstream Products

• 1557241-04-9 4-[(1R,3R)-3-{[(5-fluoro-2-methylphenyl)amino]methyl}-2,2-dimethylcyclopropyl]benzenesulfonamide 

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.