1369769-35-6

Usage

Uses

Used in Pharmaceutical Industry:
(1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)cyclopropanecarboxylic acid is used as a potential pharmaceutical compound for its possible applications in medicinal chemistry research. Its unique structure and properties make it a candidate for the development of new drugs, potentially offering novel therapeutic options for various medical conditions.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)cyclopropanecarboxylic acid serves as a valuable research tool. Its cyclopropane ring and carboxylic acid group, along with the 3-fluorophenyl and (2,4-dimethylpyrimidin-5-yl)oxy)methyl side chains, provide a foundation for exploring its interactions with biological targets and evaluating its efficacy as a potential drug molecule.

Upstream product

• 501-00-8 3-fluorophenylacetonitrile 
• 1450904-98-9 (1S,2R)-1-(3-fluorophenyl)-2-(hydroxymethyl)cyclopropane-1-carbonitrile 
• 1369767-24-7 ((1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)cyclopropyl)methanol 
• 412003-95-3 5-hydroxy-2,4-dimethylpyrimidine 
• 1369766-72-2 5-methoxy-2,4-dimethylpyrimidine 
• 1450904-96-7 5-methoxy-2,6-dimethylpyrimidin-1-ium chloride 
• 1369767-26-9 (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)cyclopropanecarbaldehyde 
• 1450904-94-5 C₁₉H₂₁FN₂O₃ 
• 1450904-92-3 ((1R,2S)-2-(3-fluorophenyl)-2-((p-tosyloxy)methyl)cyclopropyl)methyl acetate 
• 1369768-29-5 [(1R,2S)-2-(3-fluorophenyl)-2-(hydroxymethyl)cyclopropyl]-methyl acetate 
• 1369767-20-3 ((1S,2R)-1-(3-fluorophenyl)cyclopropane-1,2-diyl)dimethanol 
• 1450905-00-6 (1S,2R)-1-(3-fluorophenyl)-2-(hydroxymethyl)cyclopropane-1-carboxylic acid 

Downstream Products

• 1369763-87-0 (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methylpyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide 
• 1369766-31-3 2-[(1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)cyclopropyl]quinazolin-4(1H)-one 
• 1369764-02-2 (1R,2S)-2-[{(2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide 
• 1369768-78-4 (1R,2S)-2-(((2-methyl-4-bromomethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide 
• 1369765-96-7 (1R,2S)-2-(((2-methyl-4-hydroxymethylpyrimidin-5-yl)oxy)-methyl)-N-(5-fluoropyridin-2-yl)-2-(3-fluorophenyl)-cyclopropanecarboxamide 
• 1369769-31-2 C₁₇H₁₆ClFN₂O₂ 
• 1369766-44-8 (1R,2S)-2-{[(4-fluoromethyl-2-methylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide 
• 1369764-01-1 (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoro-4-methoxypyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide 
• 1369769-04-9 C₁₇H₁₈FN₃O₂ 
• 1369766-53-9 (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-fluoro-6-hydroxypyridin-2-yl)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 
• 1449429-80-4 (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoro-4-hydroxypyridin-2-yl)-2-(3-fluorophenyl)-cyclopropanecarboxamide 
• 1369765-88-7 (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-iodopyridin-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

METHOD FOR MANUFACTURING CYCLOPROPANE COMPOUND

The present invention provides an industrially advantageous production method of (1R,2S)-2-{[((2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide. (1R,2S)-2-{[((2,4-Dimethylpyrimidin-5-yl)oxyl}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide (compound [A]) is produced by an industrially advantageous method by a route via a novel compound. wherein each symbol is as described in the description.

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.