23020-18-0

Upstream product

• 97-71-2 ethyl (1S,2R)-2-phenylcyclopropylcarboxylate 
• 140-29-4 phenylacetonitrile 
• 96847-52-8 (1R,2S)-2-oxo-1-phenyl-3-oxabicyclo[3.1.0]hexane 
• 29667-46-7 (1S,2R)-2-phenylcyclopropylmethanol 
• 186183-64-2 (1S,2R)-1-formyl-2-phenylcyclopropane 
• 100-42-5 styrene 
• 623-73-4 diazoacetic acid ethyl ester 
• 766-94-9 vinyl phenyl ether 
• 110-82-7 cyclohexane 
• 84564-98-7 peracide phenyl-2-cyclopropane carboxyloque cis 
• 946-38-3 ethyl 2-phenylcyclopropylcarboxylate 
• 946-38-3 cis-1-ethoxycarbonyl-2-phenylcyclopropane 
• 5617-74-3 cis-1,2-cyclopropanedicarboxylic acid anhydride 
• 1078-58-6 diphenylzinc 

Downstream Products

• 5682-61-1 (1S,2R)-2-phenylcyclopropanecarboxylic acid methyl ester 
• 17650-99-6 (-)-trans-2-Phenylcyclopropylchlorid 
• 29667-47-8 (+)-(1S,2R)-1-methyl-2-phenylcyclopropane 
• 29667-46-7 (1S,2R)-2-phenylcyclopropylmethanol 
• 110659-53-5 (+)-(1'R,2'S)-2-(2'-methylcyclopropyl)aniline 
• 110659-52-4 (1'R,2'S)-1-(2'-methylcyclopropyl)-2-nitrobenzene 
• 1265913-13-0 ((1S,5R)-5-(3-methoxyphenyl)-2-azabicyclo[3.3.1]nonan-2-yl)-((1'S,2'R)-2-phenylcyclopropyl)methanone 
• 1265913-11-8 ((1R,5S)-5-(3-methoxyphenyl)-2-azabicyclo[3.3.1]nonan-2-yl)-((1'S,2'R)-2-phenylcyclopropyl)methanone 
• 1265913-27-6 (1R,5S)-5-(3-methoxyphenyl)-2-(((1'S,2'R)-2-phenylcyclopropyl)methyl)-2-azabicyclo[3.3.1]nonane 
• 1265913-28-7 (1S,5R)-5-(3-methoxyphenyl)-2-(((1'S,2'R)-2-phenylcyclopropyl)methyl)-2-azabicyclo[3.3.1]nonane 
• 1265968-41-9 3-((1R,5S)-2-(((1'S,2'R)-2-phenylcyclopropyl)methyl)-2-azabicyclo[3.3.1]nonan-5-yl)phenol 
• 1265968-42-0 3-((1S,5R)-2-(((1'S,2'R)-2-phenylcyclopropyl)methyl)-2-azabicyclo[3.3.1]nonan-5-yl)phenol 
• 1402883-28-6 2-amino-3-methyl-6-((1R,2R)-2-phenylcyclopropyl)pyrimidin-4(3H)-one 
• 1402883-30-0 2-amino-6-((1S,2R)-2-phenylcyclopropyl)pyrimidin-4(3H)-one 

Relevant academic research and scientific papers

Stereoselective Functionalization of Racemic Cyclopropylzinc Reagents via Enantiodivergent Relay Coupling

Efficient construction of optically pure molecules from readily available starting materials in a simple manner is an ongoing goal in asymmetric synthesis. As a straightforward route, transition-metal-catalyzed enantioconvergent coupling between widely available secondary alkyl electrophiles and organometallic nucleophiles has emerged as a powerful strategy to construct chiral center(s). However, the scope of racemic secondary alkylmetallic nucleophiles for this coupling remains limited in specific substrates because of the difficulties in stereoselective formation of the key alkylmetal intermediates. Here, we report an enantiodivergent strategy to efficiently achieve an array of synthetically useful chiral cyclopropanes, including chiral fluoroalkylated cyclopropanes and enantiomerically enriched cyclopropanes with chiral side chains, from racemic cyclopropylzinc reagents. This strategy relies on a one-pot, two-step enantiodivergent relay coupling process of the racemic cis-cyclopropylzinc reagents with two different electrophiles, which involves kinetic resolution of racemic cis-cyclopropylzinc reagents through a nickel-catalyzed enantioselective coupling with alkyl electrophiles, followed by a stereospecific relay coupling of the remaining enantiomeric cyclopropylzinc reagent with various electrophiles, to produce two types of functionalized chiral cyclopropanes with opposite configurations on the cyclopropane ring. These chiral cyclopropanes are versatile synthons for diverse transformations, rendering this strategy effective for obtaining structurally diversified molecules of medicinal interest.

Nickel-Catalyzed Reductive Carboxylation of Cyclopropyl Motifs with Carbon Dioxide

A nickel-catalyzed reductive carboxylation technique for the synthesis of cyclopropanecarboxylic acids has been developed. This user-friendly and mild transformation operates at atmospheric pressure of carbon dioxide and utilizes either organic halides or alkene precursors, thus representing the first example of catalytic reductive carboxylation of secondary counterparts lacking adjacent π-components.

ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS AND USES THEREOF

Disclosed are compounds of Formula (IVA), or a salt thereof, and pharmaceutical formulations (pharmaceutical compositions) comprising those compounds, or a salt thereof: Formula (IVA), wherein "RIa", "RIb", "RIc", "RId", "RIe", are defined herein above, which compounds are believed suitable for use in positive modulation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) receptors, for example, those found in the cerebral cortex and the hippocampus. Such compounds and pharmaceutical formulations are believed to be useful in treatment or management of neurodegenerative diseases, for example, Alzheimer's disease (AD), schizophrenia, and Parkinson's disease (PD), or movement disorders arising from use of certain medications used in the treatment or management of Parkinson's disease.

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.

Silver-promoted, palladium-catalyzed direct arylation of cyclopropanes: Facile access to spiro 3,3′-cyclopropyl oxindoles

The Pd-catalyzed, Ag(I)-mediated intramolecular direct arylation of cyclopropane C-H bonds is described. Various spiro 3,3′-cyclopropyl oxindoles can be obtained in good to excellent yields from easily accessible 2-bromoanilides. The kinetic isotope effect was determined and epimerization studies were conducted, suggesting that the formation of a putative Pd-enolate is not operative and that the reaction proceeds via a C-H arylation pathway.

(HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS

The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection.

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.

Probes for narcotic receptor mediated phenomena. 41. Unusual inverse μ-agonists and potent μ-opioid antagonists by modification of the N-substituent in enantiomeric 5-(3-hydroxyphenyl)morphans

Conformational restraint in the N-substituent of enantiomeric 5-(3-hydroxyphenyl)morphans was conferred by the addition of a cyclopropane ring or a double bond. All of the possible enantiomers and isomers of the N-substituted compounds were synthesized. Opioid receptor binding assays indicated that some of them had about 20-fold higher μ-affinity than the compound with an N-phenylpropyl substituent (Ki = 2-450 nM for the examined compounds with various N-substituents). Most of the compounds acted unusually as inverse agonists in the [35S]GTP-γ-S functional binding assay using nondependent cells that stably express the cloned human μ-opioid receptor. Two of the N-substituted compounds with a cyclopropane ring were very potent μ-opioid antagonists ((+)-29, Ke = 0.17 and (-)-30, Ke =0.3) in the [35S]GTP-γ-S functional binding assay. By comparison of the geometry-optimized structures of the newly synthesized compounds, an attempt was made to rationalize their μ-opioid receptor affinity in terms of the spatial position of N-substituents. This article not subject to U.S. Copyright. Published 2011 by the American Chemical Society.

Biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and LSD2

LSD1 and LSD2 histone demethylases are implicated in a number of physiological and pathological processes, ranging from tumorigenesis to herpes virus infection. A comprehensive structural, biochemical, and cellular study is presented here to probe the potential of these enzymes for epigenetic therapies. This approach employs tranylcypromine as a chemical scaffold for the design of novel demethylase inhibitors. This drug is a clinically validated antidepressant known to target monoamine oxidases A and B. These two flavoenzymes are structurally related to LSD1 and LSD2. Mechanistic and crystallographic studies of tranylcypromine inhibition reveal a lack of selectivity and differing covalent modifications of the FAD cofactor depending on the enantiomeric form. These findings are pharmacologically relevant, since tranylcypromine is currently administered as a racemic mixture. A large set of tranylcypromine analogues were synthesized and screened for inhibitory activities. We found that the common evolutionary origin of LSD and MAO enzymes, despite their unrelated functions and substrate specificities, is reflected in related ligand-binding properties. A few compounds with partial enzyme selectivity were identified. The biological activity of one of these new inhibitors was evaluated with a cellular model of acute promyelocytic leukemia chosen since its pathogenesis includes aberrant activities of several chromatin modifiers. Marked effects on cell differentiation and an unprecedented synergistic activity with antileukemia drugs were observed. These data demonstrate that these LSD1/2 inhibitors are of potential relevance for the treatment of promyelocytic leukemia and, more generally, as tools to alter chromatin state with promise of a block of tumor progression.

Selective 5-hydroxytryptamine 2c receptor agonists derived from the lead compound tranylcypromine: Identification of drugs with antidepressant-like action

We report here the design, synthesis, and pharmacological properties of a series of compounds related to tranylcypromine (9), which itself was discovered as a lead compound in a high-throughput screening campaign. Starting from 9, which shows modest activity as a 5-HT2C agonist, a series of 1-aminomethyl-2- phenylcyclopropanes was investigated as 5-HT2C agonists through iterative structural modifications. Key pharmacophore feature of this new class of ligands is a 2-aminomethyl-trans-cyclopropyl side chain attached to a substituted be zene ring. Among the tested compounds, several were potent and efficacious 5-HT2C receptor agonists with selectivity over both 5-HT2A and 5-HT2B receptors in functional assays. The most promising compound is 37, with 120- and 14-fold selectivity over 5-HT 2A and 5-HT2B, respectively (EC50) 585, 65, and 4.8 nM at the 2A, 2B, and 2C subtypes, respectively). In animal studies, compound 37 (10-60 mg/kg) decreased immobility time in the mouse forced swim test.