Fluoxetine

Base Information

• Chemical Name: Fluoxetine
• CAS No.: 54910-89-3
• Deprecated CAS: 52341-67-0,57226-07-0,57226-07-0
• Molecular Formula: C₁₇H₁₈F₃NO
• Molecular Weight: 309.331
• Hs Code.: 29036990
• European Community (EC) Number: 611-209-7
• NSC Number: 283480
• UNII: 01K63SUP8D
• DSSTox Substance ID: DTXSID7023067
• Nikkaji Number: J292.434J
• Wikipedia: Fluoxetine
• Wikidata: Q422244
• NCI Thesaurus Code: C506
• RXCUI: 4493
• Pharos Ligand ID: MZYFV13ALAYR
• Metabolomics Workbench ID: 42819
• ChEMBL ID: CHEMBL41
• Mol file: 54910-89-3.mol

Synonyms:Fluoxetin;Fluoxetine;Fluoxetine Hydrochloride;Lilly 110140;Lilly-110140;Lilly110140;N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine;Prozac;Sarafem

Chemical Property of Fluoxetine

Chemical Property:

• Melting Point: 158oC
• Boiling Point: 395.1 °C at 760 mmHg
• PKA: 10.05±0.10(Predicted)
• Flash Point: 192.8 °C
• PSA: 21.26000
• Density: 1.159 g/cm³
• LogP: 4.82590
• Storage Temp.: 2-8°C(protect from light)
• XLogP3: 4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 309.13404868
• Heavy Atom Count: 22
• Complexity: 308

Purity/Quality:

99%, ^*data from raw suppliers

Fluoxetine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): C,Xi
• Hazard Codes: C,Xi

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antidepressant Agents
• Canonical SMILES: CNCCC(C1=CC=CC=C1)OC2=CC=C(C=C2)C(F)(F)F
• Recent ClinicalTrials: Clinical Trial of Fluoxetine in Anxiety and Depression in Children, and Associated Brain Changes
• Recent EU Clinical Trials: PARACHUTES: Pedophilia At Risk – Acute Treatment – E-therapy vs SSRI
• Recent NIPH Clinical Trials: Study of the role of micro RNAs 16 and 135a in patients with lifelong premature ejaculation: A prospective case control study
• Uses: Fluoxetine in its hydrochloride salt form is marketed as numerous drugs, the most popular ofwhich is Prozac. Prozac is prescribed for depression, obsessive-compulsive disorder, bulimia,agoraphobia, and premenstrual dysphoric disorder (premenstrual syndrome). Prozac andother fluoxetine medications belong to a class of drugs called selective serotonin reuptakeinhibitors (SSRIs). When a nerve signal is sent, a neurotransmitter, such as serotonin, travelsfrom a presynaptic neuron across the synaptic gap to a postsynaptic neuron. Receptors on thepostsynaptic neuron capture the neurotransmitter, resulting in the transmission of the signal.After performing its function, the neurotransmitter is released back to the presynaptic cellin a process called reuptake. SSRIs slow down the return of serotonin to presynaptic neurons,allowing for a higher serotonin concentration on postsynaptic neurons. Because depressionand other psychological disorders are associated with low serotonin levels, Prozac and otherSSRIs help maintain serotonin levels.Prozac was thefirst SSRI antidepressant to be marketed. Because Prozac produced lesssevere side effects than other antidepressants, it became the drug of choice for treating depressionand was made available to a wider public. Its use exploded in the 1990s, with sales peakingin 2000 when revenues from Prozac reached $2.5 billion. Eli Lilly’s patent on fluoxetinehydrochloride expired in August 2001; its use continued into the 21st century but on a muchsmaller scale as generic fluoxetine hydrochloride products came on the market. Since its introductionin 1986, Prozac was the most prescribed drug for antidepressant until recent yearswhen it was replaced by Zoloft, Paxil, and Lexapro as the top three antidepressants prescribedin the United States, respectively.Fluoxetine hydrochloride is most recognized as an antidepressant, but it is also used torelieve symptoms of premenstrual dysphoric disorder (PMDD) (premenstrual syndrome).Th ese symptoms include mood swings, tension, bloating, irritability, and breast tenderness. EliLilly began marketing fl uoxetine hydrochloride as Sarafem in 2000 for treating PMDD. antibacterial Rivastigmine Metabolite
• Biological Functions: Fluoxetine (Prozac) is given in the morning because of its potential for being activating and causing insomnia. Food does not affect its systemic bioavailability and may actually lessen the nausea reported by some patients. Fluoxetine is highly bound to serum proteins and may interact with other highly protein bound drugs. It is demethylated in the liver to form an active metabolite, norfluoxetine. Inactive metabolites are excreted by the kidney.Doses must be reduced in patients with liver disease. The slow elimination of fluoxetine and norfluoxetine lead to special clinical concerns when adjusting doses and discontinuing this medication. Steady state is not reached until 4 to 6 weeks, and similarly, complete elimination takes 4 to 6 weeks after discontinuation of the medication. A 4- to 6-week waiting period should be permitted before starting a medication with potential for an interaction with fluoxetine, such as a monoamine oxidase inhibitor (MAOI). Additionally, fluoxetine is a potent inhibitor of cytochrome P450 2D6 and can significantly elevate levels of drugs metabolized by this route. Thus, coadministration of drugs with a narrow therapeutic index, such as TCAs and type 1C antiarrhythmics, including flecainide and propafenone, are a particular concern.
• Clinical Use: Fluoxetine is a 3-phenoxy-3-phenylpropylamine that exhibits selectivity and high affinity for human SERT and low affinity for NET. It is marketed as a racemic mixture of R- and S-fluoxetine. Its selectivity for SERT inhibition depends on the position of the substituent in the phenoxy ring.
• Drug interactions: Fluoxetine and its norfluoxetine metabolite, like many other drugs metabolized by CYP2D6, inhibit the activity of CYP2D6 and, potentially, may increase plasma concentrations of concurrently administered drugs that also are metabolized by this enzyme. Fluoxetine may make normal CYP2D6 metabolizers resemble poor metabolizers. Fluoxetine can inhibit its own CYP2D6 metabolism, resulting in higher-than-expected plasma concentrations during upward dose adjustments. Therefore, switching from fluoxetine to another SSRI or other serotonergic antidepressant requires a washout period of at least 5 weeks or a lowerthan-recommended initial dose with monitoring for adverse events. Fluoxetine is highly protein bound and may affect the free plasma concentration and, thus, the pharmacological effect of other highly protein-bound drugs (e.g., warfarin sodium).

Technology Process of Fluoxetine

There total 129 articles about Fluoxetine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

2,2,2-trifluoro-N-methyl-N-(3-phenyl-3-(4-(trifluoromethyl)phenoxy)propyl)acetamide → FLUOXETINE (54910-89-3,57226-07-0,100568-02-3,100568-03-4,59333-67-4)

Guidance literature:

With sodium hydroxide; In tetrahydrofuran; at 20 ℃; for 5h;

DOI:10.1039/c9ob02635e

Reference yield: 87.0%

3-methylamino-1-phenylpropan-1-ol (42142-52-9) + 4-chlorobenzotrifluoride (98-56-6) → FLUOXETINE (54910-89-3,57226-07-0,100568-02-3,100568-03-4,59333-67-4)

Guidance literature:

3-methylamino-1-phenylpropan-1-ol; With sodium hydride; In dimethyl sulfoxide; at 60 ℃; for 1h; Inert atmosphere;

4-chlorobenzotrifluoride; In dimethyl sulfoxide; at 100 ℃; for 10h; Inert atmosphere;

With water; In diethyl ether; dimethyl sulfoxide;

DOI:10.1080/00397910903422518

Reference yield: 86.0%

3-methylamino-1-phenylpropan-1-ol (42142-52-9) + 4-hydroxybenzotrifluoride (402-45-9) → FLUOXETINE (54910-89-3,57226-07-0,100568-02-3,100568-03-4,59333-67-4)

Guidance literature:

With tributylphosphine; di-isopropyl azodicarboxylate; In dichloromethane; N,N-dimethyl acetamide; at 70 ℃; for 0.0833333h;

DOI:10.1039/c0ob00906g

upstream raw materials:

N-benzyl-N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropyl-amine

3-(benzyl-methyl-amino)-1-phenylpropan-1-one

acetophenone

3-(N-benzyl-N-methylamino)-1-phenyl-propan-1-ol

Downstream raw materials:

(R)-fluoxetine

(S)-fluoxetine

N-(2-Oxycarbonylethyl)fluoxetin

methyl-oxiranylmethyl-[3-phenyl-3-[4-(trifluoromethyl)-phenoxy]-propyl]amine

Refernces

• 1、 Bojarski, Andrzej J.,Bugno, Ryszard,Duszyńska, Beata,Hogendorf, Adam S.,Hogendorf, Agata,Kurczab, Rafa?,Lenda, Tomasz,Pietru?, Wojciech,Sata?a, Grzegorz,Staroń, Jakub,Wantuch, Anna,Warszycki, Dawid. "Tuning the activity of known drugs via the introduction of halogen atoms, a case study of SERT ligands – Fluoxetine and fluvoxamine". . . Retrieved 2021/06/02.
• 2、 Johansen, Martin B.,Lindhardt, Anders T.. "Copper-catalyzed and additive free decarboxylative trifluoromethylation of aromatic and heteroaromatic iodides". . p. 1417 - 1425. Retrieved 2020/03/03.