3471-10-1

Usage

Uses

Used in Pharmaceutical Synthesis:
(1R)-2α-Phenylcyclopropane-1β-carboxylic acid is utilized as a key intermediate in the synthesis of various pharmaceuticals and organic compounds. Its unique structure allows it to be a valuable building block for creating new and effective medications.
Used in Medicinal Chemistry Research:
(1R)-2α-Phenylcyclopropane-1β-carboxylic acid is used as a subject of study in medicinal chemistry to understand its reactivity and biological activities. This research is crucial for exploring its potential applications in drug development and other industries.
Used in Drug Development:
Due to its potential applications in medicinal chemistry, (1R)-2α-Phenylcyclopropane-1β-carboxylic acid is employed in drug development processes. Researchers and chemists investigate its properties to harness its potential in creating innovative and effective drugs for various medical conditions.

Upstream product

• 97-71-2 (1R,2R)-2-phenyl-cyclopropanecarboxylic acid ethyl ester 
• 82263-48-7 trans-2- phenylcyclopropane-1-carbaldehyde 
• 133124-20-6 (2R,4S)-(+)-5,5-dimethyl-4-phenyl-2-(trans-2-phenylcyclopropyl)-1,3-dioxane 
• 573968-14-6 (R,R)-trans-2-phenyl-cyclopropane-1-carboxylic acid benzyl ester 
• 99267-79-5 (4R,5R)-2-((1R,2R)-2-Phenyl-cyclopropyl)-[1,3]dioxolane-4,5-dicarboxylic acid diethyl ester 
• 946-39-4 ethyl rac-(1S,2S)-2-phenylcycloproanecarboxylate 
• 939-88-8 rac-(1R,2R)-2-phenylcyclopropanecarboxamide 
• 14371-10-9 (E)-3-phenylpropenal 
• 133124-11-5 (2R,4S)-(+)-5,5-dimethyl-4-phenyl-2-(trans-2-phenylethenyl)-1,3-dioxane 
• 133127-92-1 (2S,4S)-(-)-4-(2-chlorophenyl)-5,5-dimethyl-2-(trans-2-phenylethenyl)-1,3-dioxane 
• 100-42-5 styrene 
• 263893-73-8 ((1R,4aS)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl)methanaminium (1R,2R)-2-phenylcyclopropane-1-carboxylate 
• 3234-51-3 1,1-dibromo-2-phenylcyclopropane 
• 939-90-2 trans-2-phenylcyclopropane-1-carboxylic acid 

Downstream Products

• 1265913-01-6 ((1S,5R)-5-(3-methoxyphenyl)-2-azabicyclo[3.3.1]nonan-2-yl)-((1'R,2'R)-2-phenylcyclopropyl)methanone 
• 1265913-07-2 ((1R,5S)-5-(3-methoxyphenyl)-2-azabicyclo[3.3.1]nonan-2-yl)-((1'R,2'R)-2-phenylcyclopropyl)methanone 
• 1265913-18-5 (1S,5R)-5-(3-methoxyphenyl)-2-(((1'R,2'R)-2-phenylcyclopropyl)methyl)-2-azabicyclo[3.3.1]nonane 
• 1265913-24-3 (1R,5S)-5-(3-methoxyphenyl)-2-(((1'R,2'R)-2-phenylcyclopropyl)methyl)-2-azabicyclo[3.3.1]nonane 
• 1265968-36-2 3-((1S,5R)-2-(((1'R,2'R)-2-phenylcyclopropyl)methyl)-2-azabicyclo[3.3.1]nonan-5-yl)phenol 
• 1265968-39-5 3-((1R,5S)-2-(((1'R,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 
• 1402883-32-2 2-amino-6-((1R,2R)-2-phenylcyclopropyl)pyrimidin-4(3H)-one 
• 1402883-31-1 ethyl 3-oxo-3-((1R,2R)-2-phenylcyclopropyl)propanoate 
• 95-62-5 (1R,2S)-1-amino-2-phenylcyclopropane 
• 3721-28-6 (1S,2R)-tranylcypromine 
• 185256-47-7 (-)-(1R,2S)-trans (2-phenyl-cyclopropyl)carbaminic acid tert-butyl ester 
• 105367-36-0 (1R)-menthyl (1S,2S)-(+)-2-phenylcyclopropanecarboxylate 
• 105367-37-1 (1S,2R)-l-menthyl 2-phenylcyclopropane-1-carboxylate 

Relevant academic research and scientific papers

Mild Ring-Opening 1,3-Hydroborations of Non-Activated Cyclopropanes

The Brown hydroboration reaction, first reported in 1957, is the addition of B?H across an olefin in an anti-Markovnikov fashion. Here, we solved a long-standing problem on mild 1,3-hydroborations of non-activated cyclopropanes. A three-component system including cyclopropanes, boron halides, and hydrosilanes has been developed for borylative ring-opening of cyclopropanes following the anti-Markovnikov rule, under mild reaction conditions. Density functional theory (M06-2X) calculations show that the preferred pathway involves a cationic boron intermediate which is quenched by hydride transfer from the silane.

Discovery of a Novel Inhibitor of Histone Lysine-Specific Demethylase 1A (KDM1A/LSD1) as Orally Active Antitumor Agent

We report the stereoselective synthesis and biological activity of a novel series of tranylcypromine (TCPA) derivatives (14a-k, 15, 16), potent inhibitors of KDM1A. The new compounds strongly inhibit the clonogenic potential of acute leukemia cell lines. In particular three molecules (14d, 14e, and 14g) showing selectivity versus MAO A and remarkably inhibiting colony formation in THP-1 human leukemia cells, were assessed in mouse for their preliminary pharmacokinetic. 14d and 14e were further tested in vivo in a murine acute promyelocytic leukemia model, resulting 14d the most effective. Its two enantiomers were synthesized: the (1S,2R) enantiomer 15 showed higher activity than its (1R,2S) analogue 16, in both biochemical and cellular assays. Compound 15 exhibited in vivo efficacy after oral administration, determining a 62% increased survival in mouse leukemia model with evidence of KDM1A inhibition. The biological profile of compound 15 supports its further investigation as a cancer therapeutic.

Gram-Scale Synthesis of Chiral Cyclopropane-Containing Drugs and Drug Precursors with Engineered Myoglobin Catalysts Featuring Complementary Stereoselectivity

Engineered hemoproteins have recently emerged as promising systems for promoting asymmetric cyclopropanations, but variants featuring predictable, complementary stereoselectivity in these reactions have remained elusive. In this study, a rationally driven strategy was implemented and applied to engineer myoglobin variants capable of providing access to 1-carboxy-2-aryl-cyclopropanes with high trans-(1R,2R) selectivity and catalytic activity. The stereoselectivity of these cyclopropanation biocatalysts complements that of trans-(1S,2S)-selective variants developed here and previously. In combination with whole-cell biotransformations, these stereocomplementary biocatalysts enabled the multigram synthesis of the chiral cyclopropane core of four drugs (Tranylcypromine, Tasimelteon, Ticagrelor, and a TRPV1 inhibitor) in high yield and with excellent diastereo- and enantioselectivity (98–99.9% de; 96–99.9% ee). These biocatalytic strategies outperform currently available methods to produce these drugs.

Discovery of New Potential Anti-Infective Compounds Based on Carbonic Anhydrase Inhibitors by Rational Target-Focused Repurposing Approaches

In academia, compound recycling represents an alternative drug discovery strategy to identify new pharmaceutical targets from a library of chemical compounds available in house. Herein we report the application of a rational target-based drug-repurposing approach to find diverse applications for our in-house collection of compounds. The carbonic anhydrase (CA, EC 4.2.1.1) metalloenzyme superfamily was identified as a potential target of our compounds. The combination of a thoroughly validated docking screening protocol, together with in vitro assays against various CA families and isoforms, allowed us to identify two unprecedented chemotypes as CA inhibitors. The identified compounds have the capacity to preferentially bind pathogenic (bacterial/protozoan) CAs over human isoforms and represent excellent hits for further optimization in hit-to-lead campaigns.

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.

The influence of cosolvent concentration on enzymatic kinetic resolution of trans-2-phenyl-cyclopropane-1-carboxylic acid derivatives

A method to improve the enantioselectivity of lipase-catalyzed kinetic resolution (KR) of trans-2-phenyl-cyclopropane-1-carboxylic acid derivatives in water-acetone solution is presented. Two different approaches were compared: enzyme-catalyzed esterification and enzymatic hydrolysis of the target ester. A substantial influence of enzyme type, ethoxy group donor, and solvent on conversion and enantioselectivity of the enzymatic esterification was noted. While enzymatic esterification proceeds with poor enantioselectivity, the hydrolysis of target ester proceeds efficiently. Studies on the influence of cosolvent used for the enzymatic hydrolysis reaction showed that kinetic resolution can be performed in acetone and water buffer mixture predominantly containing organic solvent. Any change in organic solvent content resulted in a substantial decrease in enantioselectivity from almost E = 150 to less than 5.

KDM1A INHIBITORS FOR THE TREATMENT OF DISEASE

Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDMIA, and methods of increasing gamma globin gene expression in a human or animal subject are also provided for the treatment diseases such as sickle cell disease.

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.

(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.