1369767-20-3

Usage

Uses

Used in Organic Synthesis:
((1S,2R)-1-(3-fluorophenyl)cyclopropane-1,2-diyl)dimethanol serves as a valuable building block in organic synthesis, contributing to the preparation of a variety of other organic compounds. Its unique structure allows it to be a versatile component in the creation of complex molecules.
Used in Medicinal Chemistry:
In the pharmaceutical industry, ((1S,2R)-1-(3-fluorophenyl)cyclopropane-1,2-diyl)dimethanol is utilized for the development of drugs that target specific biological pathways. The presence of the fluorophenyl group is particularly advantageous for enhancing the compound's interaction with biological targets, potentially leading to more effective medications.
Used in Polymer Synthesis:
The two hydroxyl groups in ((1S,2R)-1-(3-fluorophenyl)cyclopropane-1,2-diyl)dimethanol make it a useful precursor in the synthesis of polymeric materials. Its incorporation can lead to polymers with novel properties, expanding the range of applications in various industries.
Used in Surfactant and Emulsifier Development:
As a potential component in the development of new surfactants or emulsifiers, ((1S,2R)-1-(3-fluorophenyl)cyclopropane-1,2-diyl)dimethanol can improve the performance of these substances. Its unique structure and functional groups can lead to the creation of surfactants and emulsifiers with enhanced stability and effectiveness.
Overall, ((1S,2R)-1-(3-fluorophenyl)cyclopropane-1,2-diyl)dimethanol is a multifaceted compound with applications spanning across organic synthesis, medicinal chemistry, polymer science, and the development of surfactants and emulsifiers. Its unique structure and functional groups make it a promising intermediate for the production of various chemical compounds.

Upstream product

• 1450904-98-9 (1S,2R)-1-(3-fluorophenyl)-2-(hydroxymethyl)cyclopropane-1-carbonitrile 
• 1450905-00-6 (1S,2R)-1-(3-fluorophenyl)-2-(hydroxymethyl)cyclopropane-1-carboxylic acid 
• 528587-70-4 (1S,5R)-2-oxo-1-(3-fluorophenyl)-3-oxabicyclo[3.1.0]hexane 
• 501-00-8 3-fluorophenylacetonitrile 

Downstream Products

• 1369767-21-4 {(1S,2R)-[2-(tert-butyldiphenylsilyloxymethyl)-1-(3-fluorophenyl)cyclopropyl]}methanol 
• 1450904-92-3 ((1R,2S)-2-(3-fluorophenyl)-2-((p-tosyloxy)methyl)cyclopropyl)methyl acetate 
• 1450904-94-5 C₁₉H₂₁FN₂O₃ 
• 1369767-24-7 ((1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)cyclopropyl)methanol 
• 1369767-26-9 (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)cyclopropanecarbaldehyde 
• 1369769-35-6 (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)cyclopropanecarboxylic acid 
• 1369764-02-2 (1R,2S)-2-[{(2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide 
• 1369768-29-5 [(1R,2S)-2-(3-fluorophenyl)-2-(hydroxymethyl)cyclopropyl]-methyl acetate 
• 1369768-30-8 C₁₅H₁₇FO₄ 
• 1369763-87-0 (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methylpyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide 
• 1369768-78-4 (1R,2S)-2-(((2-methyl-4-bromomethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide 
• 1449429-80-4 (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoro-4-hydroxypyridin-2-yl)-2-(3-fluorophenyl)-cyclopropanecarboxamide 
• 1369769-05-0 (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-fluoro-6-methoxypyridin-2-yl)cyclopropanecarboxamide 
• 1369764-03-3 (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-cyanopyridin-2-yl)cyclopropanecarboxamide 

Relevant academic research and scientific papers

Discovery of (1R,2S)-2-{[(2,4-Dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006): A Potent and Efficacious Oral Orexin Receptor Antagonist

The orexin/hypocretin receptors are a family of G protein-coupled receptors and consist of orexin-1 (OX1) and orexin-2 (OX2) receptor subtypes. Orexin receptors are expressed throughout the central nervous system and are involved in the regulation of the sleep/wake cycle. Because modulation of these receptors constitutes a promising target for novel treatments of disorders associated with the control of sleep and wakefulness, such as insomnia, the development of orexin receptor antagonists has emerged as an important focus in drug discovery research. Here, we report the design, synthesis, characterization, and structure-activity relationships (SARs) of novel orexin receptor antagonists. Various modifications made to the core structure of a previously developed compound (-)-5, the lead molecule, resulted in compounds with improved chemical and pharmacological profiles. The investigation afforded a potential therapeutic agent, (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006), an orally active, potent orexin antagonist. The efficacy was demonstrated in mice in an in vivo study by using sleep parameter measurements. (Chemical Equation Presented).

METHODS AND COMPOUNDS USEFUL IN THE SYNTHESIS OF OREXIN-2 RECEPTOR ANTAGONISTS

The present disclosure provides compounds and methods that are useful for the preparation of compounds useful as orexin-2 receptor antagonists.

Synthesis and evaluation of novel radioligands for positron emission tomography imaging of the orexin-2 receptor

Orexin receptors (OXRs) in the brain have been implicated in diverse physiological and neuropsychiatric conditions. Here we describe the design, synthesis, and evaluation of OXR ligands related to (1R,2S)-2-(((2-methyl-4- methoxymethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyridin-2-yl) -2-(3-fluorophenyl)cyclopropanecarboxamide (9a) applicable to positron emission tomography (PET) imaging. Structural features were incorporated to increase binding affinity for OXRs, to enable carbon-11 radiolabeling, and to adjust lipophilicity considered optimal for brain penetration and low nonspecific binding. 9a displayed nanomolar affinity for OXRs, and autoradiography using rat brain sections showed that specific binding of [11C]9a was distributed primarily to neocortical layer VI and hypothalamus, consistent with reported localizations of orexin-2 receptors (OX2Rs). In vivo PET study of [11C]9a demonstrated moderate uptake of radioactivity into rat and monkey brains under deficiency or blockade of P-glycoprotein, and distribution of PET signals in the brain was in agreement with autoradiographic data. Our approach and findings have provided significant information for development of OX2R PET tracers.

CYCLOPROPANE DERIVATIVES

A cyclopropane derivative represented by the following formula (I) or a pharmaceutically acceptable salt thereof has orexin receptor inhibitory action, and thus, is extremely useful as an agent for preventing or treating sleep disorder or dyssomnia caused by orexin, including insomnia as a typical example: wherein A1, A2 and A3 each independently represent an aryl group, a heterocyclyl group or the like, R1, R2 and R3 each independently represent a hydrogen atom, a C1-6 alkyl group or the like, X represents an oxygen atom or the like, and L represents a bond or the like.