528587-70-4

Usage

Uses

Used in Organic Synthesis:
(1S,5R)-2-oxo-1-(3-fluorophenyl)-3-oxabicyclo[3.1.0]hexane is used as a building block in organic synthesis for the creation of various complex organic molecules. Its unique structure and reactivity make it a valuable component in the synthesis of pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Medicinal Chemistry:
(1S,5R)-2-oxo-1-(3-fluorophenyl)-3-oxabicyclo[3.1.0]hexane is used as a key intermediate in the development of new drugs and pharmaceutical agents. Its unique structure and functional groups can be utilized to design and synthesize novel compounds with potential therapeutic applications.
Used in Pharmaceutical Research:
(1S,5R)-2-oxo-1-(3-fluorophenyl)-3-oxabicyclo[3.1.0]hexane is used as a research tool in pharmaceutical research to study its potential biological activity and explore its applications in drug discovery. Its stereochemistry and functional groups can provide insights into its interactions with biological targets and its potential as a therapeutic agent.
Used in Drug Discovery:
(1S,5R)-2-oxo-1-(3-fluorophenyl)-3-oxabicyclo[3.1.0]hexane is used as a starting material in drug discovery to identify and develop new drug candidates. Its unique structure and reactivity can be leveraged to design and synthesize compounds with novel mechanisms of action and potential therapeutic benefits.

Upstream product

• 51594-55-9 (R)-(-)-epichlorohydrin 
• 501-00-8 3-fluorophenylacetonitrile 
• 1450905-00-6 (1S,2R)-1-(3-fluorophenyl)-2-(hydroxymethyl)cyclopropane-1-carboxylic acid 
• 1450904-98-9 (1S,2R)-1-(3-fluorophenyl)-2-(hydroxymethyl)cyclopropane-1-carbonitrile 

Downstream Products

• 528587-78-2 (1S,2R)-1-(3-fluorophenyl)-2-(hydroxymethyl)-N,N-diethylcyclopropanecarboxamide 
• 1369768-29-5 [(1R,2S)-2-(3-fluorophenyl)-2-(hydroxymethyl)cyclopropyl]-methyl acetate 
• 1369768-30-8 C₁₅H₁₇FO₄ 
• 1450904-92-3 ((1R,2S)-2-(3-fluorophenyl)-2-((p-tosyloxy)methyl)cyclopropyl)methyl acetate 
• 1450904-94-5 C₁₉H₂₁FN₂O₃ 
• 1369767-26-9 (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)cyclopropanecarbaldehyde 
• 1369764-02-2 (1R,2S)-2-[{(2,4-dimethylpyrimidin-5-yl)oxy}methyl]-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide 
• 1369764-01-1 (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoro-4-methoxypyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide 
• 1369768-06-8 C₁₈H₁₉FN₂O₄ 
• 1449429-88-2 C₁₈H₂₀FN₃O₃ 
• 1369764-98-6 (1R,2S)-2-(((2-methyl-4-methoxymethylpyrimidin-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 
• 1369769-04-9 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 

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).

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.

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.

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.

Identification of 1S,2R-milnacipran analogs as potent norepinephrine and serotonin transporter inhibitors

A series of milnacipran analogs were synthesized and studied as monoamine transporter inhibitors, and several potent compounds with moderate lipophilicity were identified from the 1S,2R-isomers. Thus, 15l exhibited IC50 values of 1.7 nM at NET and 25 nM at SERT, which were, respectively, 20- and 13-fold more potent than 1S,2R-milnacipran 1-II.

CYCLOPROPYL DERIVATIVES AS NK3 RECEPTOR ANTAGONISTS

The present invention relates to cyclopropyl derivatives of formula (I) and salt thereof. These compounds are NK3 receptor antagonists and may therefore be useful for treatment of diseases where the NK3 receptor is implicated, e.g. psychotic disorders.

Synthesis of derivatives of (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC) modified at the 1-aromatic moiety as novel NMDA receptor antagonists: The aromatic group is essential for the activity

(1S,2R)-1-Phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (PPDC, 4a), which is a conformationally restricted analogue of antidepressant milnacipran [(±)-1], is a new class of potent noncompetitive NMDA receptor antagonists. A series of PPD