82248-59-7 Usage
Description
Atomoxetine hydrochloride is a selective norepinephrine reuptake inhibitor, which is the R-stereoisomer of the racemate tomoxetine. It is the first non-stimulant marketed for the treatment of attention deficit hyperactivity disorder (ADHD) and has little effect on dopamine and serotonin reuptake or other receptors. It is prepared through a selective enzymatic acylation process and has been demonstrated to selectively inhibit norepinephrine reuptake in vivo preclinically.
Uses
Used in Pharmaceutical Industry:
Atomoxetine hydrochloride is used as a norepinephrine reuptake inhibitor for the treatment of attention-deficit hyperactivity disorder (ADHD) in children, adolescents, and adults. It helps to increase extracellular norepinephrine and dopamine levels in the rat prefrontal cortex, reducing impulsivity and improving cognitive function.
Used as a Psychotherapeutic and Anti-Depressant:
Atomoxetine hydrochloride is used as a psychotherapeutic agent and an antidepressant, providing neuroprotective effects when administered prior to ischemic damage in a gerbil model of transient cerebral ischemia.
Used in Analytical Applications:
Atomoxetine hydrochloride is used as a pharmaceutical reference standard for several analytical applications, including pharmaceutical release testing, method development for qualitative and quantitative analyses, food and beverage quality control testing, and other calibration requirements. It may be used for the determination of atomoxetine hydrochloride in pharmaceutical formulations by spectrophotometric methods.
Used in Research:
(R)-Tomoxetine hydrochloride has been used as a noradrenaline reuptake inhibitor in research studies to investigate the role of L-threo-3,4-dihydroxyphenylserine (L-DOPS) in the pathogenesis of Alzheimer's disease in mice, study its effects on set shifting in rats, and examine its effects on rat brain as a result of long-term use.
Originator
Eli Lilly & Co (US)
Biological Activity
Potent and selective noradrenalin re-uptake inhibitor (K i values are 5, 77 and 1451 nM for inhibition of radioligand binding to human NET, SERT and DAT respectively). Displays minimal affinity for a range of other neurotransmitter receptors and transporters (K i > 1 μ M). Antidepressant.
Synthesis
The 3-aryloxy substituent
was introduced utilizing a chiral alcohol by either the
Mitsunobu reaction or by nucleophilic aromatic
displacement. Because of the expense and difficulty of the
Mitsunobu reaction on large scale, the commercial process
adopts the nucleophilic aromatic substitution method. 3-
Chloropropiophenone (37) was asymmetrically reduced with
borane and catalytic amount of (S)-oxazaborolidine (8) in
THF at 0°C to give chiral alcohol 38 in 99% yield and 94% e.e. The chiral alcohol was further purified by recrystallization
to greater than 99% e.e.. Subsequent treatment
of chloride 38 with excess dimethylamine (40% in water) in
ethanol gave dimethylamine alcohol 39 in 90% yield.
Alcohol 39 was then subjected to nucleophilic aromatic
displacement in the presence of NaH in DMSO with 1-
fluoro-2-(t-butylimino)benzene (41), which was prepared in
high yield from 2-fluorobenzaldehyde (40). The
displacement product 42 was obtained in 98% yield, and the
imine 42 was subsequently hydrolyzed with acetic acid in
water at low temperature to give the corresponding aldehyde
43 in 96% yield. Sodium borohydride was employed to
reduce aldehyde 43 to alcohol in cold methanol and the
intermediate alcohol was converted to chloride 44 with
thionyl chloride. Chloride 44 was then reduced with zinc
metal under acidic conditions to give methyl adduct 45 in
95% yield and 94% e.e. Finally, phenyl chloroformate and
triethylamine was used to transform dimethylamine 45 to
monomethyl amine, which was subsequently treated with
HCl in EtOAc under reflux to give atomoxetin
hydrochloride (IV) in 98% yield and 99% e.e. from 45.
Check Digit Verification of cas no
The CAS Registry Mumber 82248-59-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,2,2,4 and 8 respectively; the second part has 2 digits, 5 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 82248-59:
(7*8)+(6*2)+(5*2)+(4*4)+(3*8)+(2*5)+(1*9)=137
137 % 10 = 7
So 82248-59-7 is a valid CAS Registry Number.
InChI:InChI=1/C17H21NO.ClH/c1-14-8-6-7-11-16(14)19-17(12-13-18-2)15-9-4-3-5-10-15;/h3-11,17-18H,12-13H2,1-2H3;1H
82248-59-7Relevant articles and documents
Preparation method of cefamoxetine hydrochloride
-
, (2021/10/27)
The invention discloses a preparation method of tamoxidectin hydrochloride, belongs to the technical field of drug synthesis, and uses 3 - chlorine -1 - phenylpropanone as a raw material to undergo a reduction reaction. The synthesis route has the advantages of few reaction steps, mild reaction conditions,3 - simple 2 - operation, cheap -3 - and easily available raw materials, and low production cost 3 - and -1 - R-chloro - N - phenylpropanone is used as a raw material.
R-(-)-atomoxetine hydrochloride preparation method
-
Paragraph 0087; 0091-0093; 0097-0099; 0103-0104; 0109, (2019/09/14)
The invention provides an R-(-)-atomoxetine hydrochloride preparation method, which comprises: preparing 3-methylamino-1-phenyl-1-propanol by using 1-phenyl-2-propenyl-1-one as a starting raw material, carrying out etherification on the 3-methylamino-1-phenyl-1-propanol and o-halo toluene in an inorganic alkali environment, splitting with L-(+)-mandelic acid to obtain R-(-)-tomoxetine-S-(+)-mandelate, refining the R-(-)-tomoxetine-S-(+)-mandelate, and carrying out hydrochloride forming to obtain the R-(-)-atomoxetine hydrochloride. According to the present invention, the method eliminates theoxalate refining step so as to reduce the reaction step, has advantages of cheap and easily available raw materials, less side reactions, low toxicity of the reaction solvent, high yield, high purity,low cost and the like, and is suitable for industrial production.
Preparation for atomoxetine hydrochloride
-
Paragraph 0023, (2019/01/05)
The invention belongs to the technical field of medicine, and particularly relates to a method for preparing atomoxetine hydrochloride with an N-methyl-3-phenoxy-benzenepropanamine content of less than 0.2%. The atomoxetine hydrochloride is a first non-excitatory drug used for treatment of attention deficit hyperactivity disorder in children and a high-selectivity norepinephrine reuptake inhibitor, has very low affinity with other neurotransmitters and does not induce a tic syndrome or increase movement disorders; and the N-methyl-3-phenoxy-benzenepropanamine is a impurity of an atomoxetine hydrochloride process and very difficult to remove by refining due to structural similarity, according to an European Pharmacopoeia, the content of the N-methyl-3-phenoxy-benzenepropanamine is not higher than 0.3, and the method disclosed by the invention can effectively control the content of the N-methyl-3-phenoxy-benzenepropanamine in the product, and improve quality of the medicine.