Atomoxetine hydrochloride

Base Information

• Chemical Name: Atomoxetine hydrochloride
• CAS No.: 82248-59-7
• Molecular Formula: C17H22ClNO
• Molecular Weight: 291.821
• Hs Code.: 29221990
• European Community (EC) Number: 629-925-3
• UNII: 57WVB6I2W0
• DSSTox Substance ID: DTXSID2044266
• Wikidata: Q27225729
• NCI Thesaurus Code: C47405
• RXCUI: 353103
• ChEMBL ID: CHEMBL1702
• Mol file: 82248-59-7.mol

Synonyms:139603, LY;atomoxetine;Atomoxetine HCl;atomoxetine hydrochloride;HCl, Atomoxetine;Hydrochloride, Atomoxetine;LY 139603;N-methyl-gamma-(2-methylphenoxy)benzenepropanamine hydrochloride;Strattera;tomoxetine;Tomoxetine Hydrochloride, (+)-isomer - T351671;tomoxetine hydrochloride, (+-)-isomer;tomoxetine hydrochloride, (-)-isomer

Chemical Property of Atomoxetine hydrochloride

Chemical Property:

• Appearance/Colour: solid
• Vapor Pressure: 2.95E-06mmHg at 25°C
• Melting Point: 167-169oC
• Boiling Point: 389 °C at 760 mmHg
• PKA: 10.13(at 25℃)
• Flash Point: 164.1 °C
• PSA: 21.26000
• LogP: 4.91750
• Storage Temp.: 2-8°C
• Solubility.: soluble in Methanol
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 6
• Exact Mass: 291.1389920
• Heavy Atom Count: 20
• Complexity: 237

Purity/Quality:

99.9% ^*data from raw suppliers

Atomoxetine, Hydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s): F,T
• Hazard Codes: F,T
• Statements: 11-23/24/25-39/23/24/25
• Safety Statements: 22-24/25-45-36/37-16-7

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=CC=CC=C1OC(CCNC)C2=CC=CC=C2.Cl
• Isomeric SMILES: CC1=CC=CC=C1O[C@H](CCNC)C2=CC=CC=C2.Cl
• Recent ClinicalTrials: Atomoxetine PBPK-PD Clinical Study
• Recent EU Clinical Trials: Crossover, Double-blind, Phase 2 Study of a Fixed Dose Combination of Atomoxetine and Acetazolamide Versus Placebo in Obesity Hypoventilation Syndrome
• Description: Atomoxetine is the first non-stimulant marketed for the treatment of attention deficit hyperactivity disorder (ADHD). It is the R-stereoisomer of the racemate tomoxetine and is a selective and potent norepinephrine uptake inhibitor (Ki=0.7–1.9 nM) that is devoid of binding to monoamine receptor. It also has little effect on dopamine and serotonin reuptake or acetylcholine, H1 histamine, alpha1 or alpha1-adrenergic or dopamine receptors. It is prepared from racemic 1-phenylbut-3-en-1-ol via a selective enzymatic acylation leaving the desired S-stereoisomer as the alcohol. This alcohol is converted via a Mitsunobu reaction with ortho-cresol to the corresponding ether with isomeric R-configuration. Ozonolysis and reduction steps provided the terminal alcohol that is mesylated and displaced with methylamine. Its selectivity for norepinephrine relative to dopamine inhibition was demonstrated in vivo preclinically. In a two-lever (two condition) discriminative stimulus effect study in squirrel monkeys, tomoxetine and other norepinephrine uptake inhibitors substituted for cocaine under low-dose training conditions, whereas dopamine uptake inhibitors substituted for cocaine in both low and high-dose conditions. In clinical ADHD studies in adolescents, it was significantly different from placebo in 1.2 and 1.8 mpk/day dosing. In the clinical study in adults using the CAARS scale a 95 mg/day dose provided greater than 30% improvement in total scores. Atomoxetine is about 63% orally bioavailable, is highly protein bound (98%, primarily to albumin) and has a half-life of about 5.2 h. It is metabolized by CYP2D6 resulting in differential clearance for poor metabolizers (halflife of 19 h with a 10 times higher AUC) relative to extensive metabolizers. The total daily dose for children, adolescents and adults is a maximum of 100 mg/day. Common side effects in children and adults include nausea, decreased appetite, and dizziness. Adults may also have insomnia. Atomoxetine is a selective norepinephrine reuptake inhibitor with Ki values of 5, 77, and 1,451 nM for norepinephrine, serotonin, and dopamine transporters, respectively. It is selective over the choline, GABA, and adenosine transporters, and a number of neurotransmitter receptors, ion channels, second messengers, and brain/gut peptides. In the rat prefrontal cortex (PFC), it increases extracellular norepinephrine and dopamine by 3-fold and increases Fos expression. Atomoxetine (0.1, 0.5, and 1 mg/kg) reduces premature responding, a measure of impulsivity, by rats in the 5-choice serial reaction time test (5CSRTT) in a dose-dependent manner. It also has neuroprotective effects when administered prior to ischemic damage in a gerbil model of transient cerebral ischemia. Formulations containing atomoxetine have been used in the treatment of attention-deficit hyperactivity disorder (ADHD) in children, adolescents, and adults.
• Uses: A Norepinephrine reuptake inhibitor Psychotherapeutic, Anti Depressant These Secondary Standards are qualified as Certified Reference Materials. These are suitable for use in several analytical applications including but not limited to pharma release testing, pharma method development for qualitative and quantitative analyses, food and beverage quality control testing, and other calibration requirements.Atomoxetine hydrochloride may be used as a pharmaceutical reference standard for the determination of atomoxetine hydrochloride in pharmaceutical formulations by spectrophotometric method. (R)-Tomoxetine hydrochloride has been used as a noradrenaline reuptake inhibitor:to study the role of L-threo-3,4-dihydroxyphenylserine (L-DOPS) in the pathogenesis of Alzheimer′s disease in miceto study its effects on set shifting in ratsto study its effects on rat brain as a result of its long-term use

Technology Process of Atomoxetine hydrochloride

There total 40 articles about Atomoxetine hydrochloride 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: 99.8%

(R)-tomoxetine (105314-52-1,105314-53-2,63940-51-2,83015-26-3) → atomoxetine hydrochloride (82248-59-7,82857-40-7)

Guidance literature:

With hydrogenchloride; In diethyl ether;

DOI:10.1016/j.tet.2004.12.059

Reference yield: 99.0%

ortho-methylphenyl iodide (615-37-2) + (R)-N-methyl-3-phenyl-3-hydroxypropylamine (115290-81-8) → atomoxetine hydrochloride (82248-59-7,82857-40-7)

Guidance literature:

ortho-methylphenyl iodide; (R)-N-methyl-3-phenyl-3-hydroxypropylamine; With potassium carbonate; copper(l) iodide; In toluene; at 148 ℃; for 21h; Heating / reflux;

With hydrogenchloride; In water; pH=1 - 2;

With sodium hydroxide; In water; pH=11 - 12;

Reference yield: 97.0%

(R)-tomoxetine (S)-(+)-mandelate (83113-55-7) → atomoxetine hydrochloride (82248-59-7,82857-40-7)

Guidance literature:

(R)-tomoxetine (S)-(+)-mandelate; In ethyl acetate; at 20 ℃; Heating / reflux;

With hydrogenchloride; In acetic acid butyl ester; at 15 - 20 ℃; for 2h; Product distribution / selectivity;

upstream raw materials:

(-)-N-tert-butoxycarbonyl-N-methyl-3-phenyl-3-(2-methylphenoxy)propanamine

ortho-cresol

(R)-N-methyl-3-phenyl-3-hydroxypropylamine

-(-)-1-chloro-3-phenyl-3-(2-methylphenoxy)propane

Downstream raw materials:

(-)-N-tert-butoxycarbonyl-N-methyl-3-phenyl-3-(2-methylphenoxy)propanamine

Refernces

• 1、 -. "Preparation method of atomoxetine hydrochloride". Paragraph 0015. . Retrieved 2020/06/09.
• 2、 -. "R-(-)-atomoxetine hydrochloride preparation method". Paragraph 0087; 0091-0093; 0097-0099; 0103-0104; 0109. . Retrieved 2019/09/14.