59333-67-4

Usage

Uses

Used in Pharmaceutical Industry:
Fluoxetine hydrochloride is used as an antidepressant for treating major depressive disorder, obsessive-compulsive disorder, bulimia nervosa, panic disorder, and other related conditions. It works by inhibiting the reuptake of serotonin, a neurotransmitter associated with mood regulation, leading to an improvement in the patient's mental health.
Used as a 5-HT uptake inhibitor:
In addition to its primary use as an antidepressant, fluoxetine hydrochloride is also utilized as a 5-HT (serotonin) uptake inhibitor. This application is significant in the treatment of various psychiatric and mood disorders, as it helps to regulate serotonin levels in the brain, contributing to a more balanced emotional state.

Veterinary Drugs and Treatments

Fluoxetine may be beneficial for the treatment of canine aggression, stereotypic behaviors (and other obsessive-compulsive behaviors), and anxiety. It may be useful in cats for the aforementioned behaviors and, additionally, for inappropriate elimination.

InChI:InChI=1S/C17H18F3NO.ClH/c1-21-12-11-16(13-5-3-2-4-6-13)22-15-9-7-14(8-10-15)17(18,19)20;/h2-10,16,21H,11-12H2,1H3;1H

Upstream product

• 98-86-2 acetophenone 
• 74681-55-3 3-(N-benzyl-N-methylamino)-1-phenyl-propan-1-ol 
• 42142-52-9 3-methylamino-1-phenylpropan-1-ol 
• 98-56-6 4-chlorobenzotrifluoride 
• 204704-95-0 C₂₀H₂₂F₃NO₃ 
• 402-45-9 4-hydroxybenzotrifluoride 
• 936-59-4 3-chloropropiophenone 
• 18776-12-0 3-chloro-1-phenyl-propan-1-ol 
• 62872-58-6 3-iodo-1-phenyl-propan-1-ol 
• 1170733-40-0 S-2-bromoethyl methyl(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)carbamothioate 
• 1170733-39-7 S-2-hydroxyethyl methyl(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)carbamothioate 
• 56296-78-7 Adofen 
• 2687-12-9 cinnamyl chloride 
• 1542455-00-4 3-phenyl-3-(4-(trifluoromethyl) phenoxy) propan-1-ol 

Downstream Products

• 54910-89-3 (R)-fluoxetine 
• 100568-02-3 (S)-fluoxetine 
• 199188-97-1 N-methyl-N-(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)formamide 
• 372198-81-7 N-(2-Oxycarbonylethyl)fluoxetin 
• 200006-83-3 N-[3-phenyl-3-(4-trifluoromethylphenoxy)propyl]sarcosine ethyl ester 
• 1092361-69-7 C₁₈H₁₇F₃NOS₂^(1-)*Na⁽¹⁺⁾ 
• 1214752-96-1 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 3-(methyl(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl) amino)propanoate 
• 114414-02-7 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine oxalate 
• 23580-89-4 methyl-(3-phenyl-propyl)-amine 
• 868944-54-1 3-(methyl(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)amino)propan-1-ol 
• 159216-80-5 N-benzyl-N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropyl-amine 

Relevant academic research and scientific papers

Truly-Biocompatible Gold Catalysis Enables Vivo-Orthogonal Intra-CNS Release of Anxiolytics

Being recognized as the best-tolerated of all metals, the catalytic potential of gold (Au) has thus far been hindered by the ubiquitous presence of thiols in organisms. Herein we report the development of a truly-catalytic Au-polymer composite by assembling ultrasmall Au-nanoparticles at the protein-repelling outer layer of a co-polymer scaffold via electrostatic loading. Illustrating the in vivo-compatibility of the novel catalysts, we show their capacity to uncage the anxiolytic agent fluoxetine at the central nervous system (CNS) of developing zebrafish, influencing their swim pattern. This bioorthogonal strategy has enabled -for the first time- modification of cognitive activity by releasing a neuroactive agent directly in the brain of an animal.

Tuning the activity of known drugs via the introduction of halogen atoms, a case study of SERT ligands – Fluoxetine and fluvoxamine

The selective serotonin reuptake inhibitors (SSRIs), acting at the serotonin transporter (SERT), are one of the most widely prescribed antidepressant medications. All five approved SSRIs possess either fluorine or chlorine atoms, and there is a limited number of reports describing their analogs with heavier halogens, i.e., bromine and iodine. To elucidate the role of halogen atoms in the binding of SSRIs to SERT, we designed a series of 22 fluoxetine and fluvoxamine analogs substituted with fluorine, chlorine, bromine, and iodine atoms, differently arranged on the phenyl ring. The obtained biological activity data, supported by a thorough in silico binding mode analysis, allowed the identification of two partners for halogen bond interactions: the backbone carbonyl oxygen atoms of E493 and T497. Additionally, compounds with heavier halogen atoms were found to bind with the SERT via a distinctly different binding mode, a result not presented elsewhere. The subsequent analysis of the prepared XSAR sets showed that E493 and T497 participated in the largest number of formed halogen bonds. The XSAR library analysis led to the synthesis of two of the most active compounds (3,4-diCl-fluoxetine 42, SERT Ki = 5 nM and 3,4-diCl-fluvoxamine 46, SERT Ki = 9 nM, fluoxetine SERT Ki = 31 nM, fluvoxamine SERT Ki = 458 nM). We present an example of the successful use of a rational methodology to analyze binding and design more active compounds by halogen atom introduction. ‘XSAR library analysis’, a new tool in medicinal chemistry, was instrumental in identifying optimal halogen atom substitution.

Systems and methods for synthesizing chemical products, including active pharmaceutical ingredients

Systems and methods for synthesizing chemical products, including active pharmaceutical ingredients, are provided. Certain of the systems and methods described herein are capable of manufacturing multiple chemical products without the need to fluidically connect or disconnect unit operations when switching from one making chemical product to making another chemical product.

Copper-catalyzed and additive free decarboxylative trifluoromethylation of aromatic and heteroaromatic iodides

A copper-catalyzed decarboxylative trifluoromethylation of (hetero)aromatic iodides has been developed. Importantly, this new copper-catalyzed reaction operates in the absence of any ligands and metal additives. The protocol shows good functional group tolerance and is compatible with heteroaromatic systems. The reaction proved scalable to a 15 mmol scale with increased yield. Finally, late-stage installation of the trifluoromethyl functionality afforded the N-trifluoroacetamide variant of the antidepressant agent, Prozac, demonstrating the applicability of the developed method.

Determination of fluoxetine hydrochloride via ion-pair complexation with alizarin red S

Two UV-Vis spectrophotometric methods and one fluorimetric method have been developed for the quantitative determination of fluoxetine hydrochloride in bulk and pharmaceutical formulations. These methods are based on the ion-pair complex formation between alizarin red S and fluoxetine hydrochloride. In the first method (method A), the yellow-colored complex obtained in acidic medium was extracted with chloroform and the absorbance of the chloroformic solution was measured at 425 nm. Beerís law limits (9.5 ? 48 μg/mL), the molar absorptivity (5256 L ∑ mol-1 ∑ cm-1), and the complex composition (1: 1) were determined. In the second method (method B), the yellow complex fluoxetine ? alizarin red S extracted in chloroform was broken in alkaline medium, and the absorbance of the resulting violet-colored free dye was measured at 524 nm. A linear relationship was observed in the range of 9.0 ? 54 μg/mL. In the third method (method C) the fluorescence intensity of the fluoxetine ? alizarin red S complex, obtained in the same manner as for method A, was measured at 594 nm after excitation at 425 nm. The fluorescence intensity was proportional to the drug concentration in the linear range of 2.7-10.2 μg/mL. The limits of detection and quantification have also been calculated. Furthermore, the proposed methods have been successfully applied for the assay of the drug in pharmaceutical dosage forms.

Fe(OTf)3-catalyzed tandem Meyer-Schuster rearrangement/intermolecular hydroamination of 3-aryl propargyl alcohols for the synthesis of acyclic β-Aminoketones

Fe(OTf)3-catalyzed synthesis of acyclic β-aminoketones from 3-aryl propargyl alcohols and nitrogen nucleophiles were investigated. Results showed that propargyl alcohols without bulky groups α to the hydroxyl group underwent the transformation smoothly. Sulphonamides exhibited the higher reactivity than amides as the nitrogen nucleophiles and the transformation of acyclic β-aminoketones were finished in shorter reaction time and higher yields. Finally, racemic fluoxetine was efficiently accessed with the present reaction as the first step. This novel synthesis of acyclic β-aminoketones probable proceeded a Fe(OTf)3-catalyzed Meyer-Schuster rearrangement of 3-aryl propargyl alcohols, followed by a intermolecular hydroamination between nitrogen nucleophiles and α, β-unsaturated ketones.

A model target anti-tumor medicament and its preparation method and application (by machine translation)

This invention relates to the targeting of antineoplastic eEF2K of a small molecule inhibitor, its formula (I), formula (II) the structure of the formula (III): Formula (I), formula (II) compound of the formula (III) structure and its pharmaceutically acceptable salt thereof can kill cancer cells, the healthy organism cells are not affected, to various tumor is markedly inhibited, in particular breast cancer, glioma, stomach cancer, liver cancer cells is markedly inhibited. (by machine translation)

Total synthesis of fluoxetine and duloxetine through an in situ imine formation/borylation/transimination and reduction approach

We report efficient, catalytic, asymmetric total syntheses of both (R)-fluoxetine and (S)-duloxetine from α,β-unsaturated aldehydes conducting five sequential one-pot steps (imine formation/copper mediated β-borylation/transimination/reduction/oxidation) followed by the specific ether group formation which deliver the desired products (R)-fluoxetine in 45% yield (96% ee) and (S)-duloxetine in 47% yield (94% ee). This journal is the Partner Organisations 2014.

From precursor to catalyst: The involvement of [Ru(η5-Cp?)Cl2]2 in highly branch selective allylic etherification of cinnamyl chlorides

(RuCp?Cl2)2, a general entry into Cp?Ru sandwich and half-sandwich chemistry was first used as a precatalyst in allylic etherification of cinnamyl chlorides with up to 98:2 regioselectivity (19 examples). Both the solvent effect and the exsiccant reaction condition are crucial to the reactivity and selectivity. Preliminary mechanism studies and the demonstration of Fluoxetine synthesis were presented in this work as well.

Molecular basis for selective serotonin reuptake inhibition by the antidepressant agent fluoxetine (Prozac)

Inhibitors of the serotonin transporter (SERT) are widely used antidepressant agents, but the structural mechanism for inhibitory activity and selectivity over the closely related norepinephrine transporter (NET) is not well understood. Here we use a combination of chemical, biological, and computational methods to decipher the molecular basis for high-affinity recognition in SERT and selectivity over NET for the prototypical antidepressant drug fluoxetine (Prozac; Eli Lilly, Indianapolis, IN). We show that fluoxetine binds within the central substrate site of human SERT, in agreement with recent X-ray crystal structures of LeuBAT, an engineered monoamine-like version of the bacterial amino acid transporter LeuT. However, the binding orientation of fluoxetine is reversed in our experimentally supported model comparedwith the LeuBAT structures, emphasizing the need for careful experimental verification when extrapolating findings from crystal structures of bacterial transporters to human relatives. We find that the selectivity of fluoxetine and nisoxetine, a NET selective structural congener of fluoxetine, is controlled by residues in different regions of the transporters, indicating a complex mechanism for selective recognition of structurally similar compounds in SERT and NET. Our findings add important new information on the molecular basis for SERT/NET selectivity of antidepressants, and provide the first assessment of the potential of LeuBAT as a model system for antidepressant binding in human transporters, which is essential for future structure-based drug development of antidepressant drugs with fine-tuned transporter selectivity. Copyright