93413-69-5 Usage
Synthesis
To a suspension of Mg (0.114 g, 4.75 mmol) in THF (2 ml) a solution
of dibromopentane 66 (0.536 g, 2.33 mmol) in THF (2 ml) was added
drop-wise at 0-5 oC. After addition, the reaction mixture was allowed
to warm to room temperature and stirred for 1.5 hours. Again, the
reaction mixture was cooled to 0-5 oC and a solution of amino ester 39
(0.45 g, 1.79 mmol) in THF (5 ml) was added to it drop-wise. After
the addition, the reaction mixture was first allowed to come to room temperature within 0.5
hour and then refluxed for 3.5 hours. The reaction mixture was allowed to cool and 50%
aq. NaOH solution was added to the reaction mixture (pH = 12), extracted with ethyl
acetate (50 ml x 2), washed with water, brine, dried over anhydrous Na2SO4, filtered and
concentrated in vacuo. The residue was purified by flash column chromatography (5%
MeOH in CHCl3) to furnish venlafaxine 14 as a colourless solid (0.25 g).
Chemical Properties
White Solid
Uses
Different sources of media describe the Uses of 93413-69-5 differently. You can refer to the following data:
1. A optically active version of Venlafaxine, a selective serotonin noradrenaline reuptake inhibitor. Used as an antidepressant
2. antidepressant;serotonin-norepinephrine reuptake inhibitor
3. A selective serotonin noradrenaline reuptake inhibitor. Used as an antidepressant.
Definition
ChEBI: A tertiary amino compound that is N,N-dimethylethanamine substituted at position 1 by a 1-hydroxycyclohexyl and 4-methoxyphenyl group.
Brand name
Effexor (Wyeth).
Biological Functions
Venlafaxine (Effexor) inhibits the reuptake of both
serotonin and norepinephrine at their respective presynaptic
sites.This drug does not have significant effects at
muscarinic, histamine, or α-adrenergic receptors and
therefore is devoid of many of the side effects associated
with the TCAs.Venlafaxine and its active metabolite O-desmethyl-venlafaxine, have half lives of 5 and
11 hours respectively, so dosing twice a day is necessary.
However, an extended release preparation (Effexor
XR) now allows for once-daily dosing and better tolerance.
Venlafaxine has a side effect profile similar to that
of the SSRIs. Higher doses of venlafaxine
result in modest increases in blood pressure in approximately
5% of patients.Venlafaxine has minimal effects
on the cytochrome P450 enzyme system.
General Description
The structure and activity of venlafaxine (Effexor) are in accordwith the general SARs for the group. As expected, it isan effective antidepressant. Venlafaxine is a serotonin–norepinephrinereuptake inhibitor (SNRI).
Pharmaceutical Applications
Venlafaxine is a serotonin and noradrenalin reuptake inhibitor (SNRI) and is used as an antidepressant. Compared to tricyclic antidepressants, it lacks the antimuscarinic and sedative side effects. Nevertheless, treatment with venlafaxine can lead to a higher risk of withdrawal symptoms.
Mechanism of action
Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), have dual mechanisms of action, with
preferential affinity for 5-HT reuptake and weak inhibition of NE and dopamine reuptake. Venlafaxine is
approximately 30 times more potent as an inhibitor of SERT than of NET. Because of the 30 times
difference in transporter affinities, increasing the dose of venlafaxine from 75 to 375 mg/day can sequentially
inhibit SERT and NERT . Thus, venlafaxine displays an ascending dose-dependent antidepressant response
in contrast to the flat dose–antidepressant response curve observed with the SSRIs. This sequential action
for venlafaxine also is consistent with its dose-dependent adverse-effect profile. Its mechanism of action is
similar to imipramine.
Venlafaxine is rapidly and well absorbed, but with a bioavailability of 45%, which has been attributed to
first-pass metabolism. Food delays its absorption but does not impair the extent of absorption.
Venlafaxine is distributed into breast milk. Venlafaxine is primarily metabolized in the liver by CYP2D6 to its
primary metabolite, ODV, which is approximately equivalent in pharmacological activity and potency to venlafaxine. In vitro studies indicate that CYP3A4 also is involved in the metabolism of venlafaxine to its
minor and less active metabolite, N-desmethylvenlafaxine. Protein binding for venlafaxine and
ODV is low and is not a problem for drug interactions. In patients with hepatic impairment, elimination
half-lives were increased by approximately 30% for venlafaxine and approximately 60% for ODV. In patients with renal function impairment, elimination half-lives were increased by approximately 40
to 50% for venlafaxine and for ODV. At steady-state doses, venlafaxine and ODV exhibit dose-proportional
linear pharmacokinetics over the dose range of 75 to 450 mg/day. Steady-state concentrations of venlafaxine
and ODV are attained within 3 days with regular oral dosing. Venlafaxine and its metabolites are excreted
primarily in the urine (87%).
Clinical Use
Venlafaxine is a methoxyphenylethylamine antidepressant that resembles an open TCA with one of the
aromatic rings replaced by a cyclohexanol ring and a dimethylaminomethyl group rather than a
dimethylaminopropyl chain.
Side effects
The potential for cardiotoxicity with venlafaxine during normal use and for various toxicities in overdose
situations are key concerns. Venlafaxine displays minimal in vitro affinity for the other neural neurotransmitter
receptors and, thus, a low probability for adverse effects. To minimize GI upset (e.g., nausea), venlafaxine
can be taken with food without affecting its GI absorption. Venlafaxine should be administered as a single
daily dose with food at approximately the same time each day. The extended-release capsules should be
swallowed whole with fluid and should not be divided, crushed, chewed, or placed in water.
Whenever venlafaxine is being discontinued after more than 1 week of therapy, it generally is recommended
that the patient be closely monitored and the dosage of the drug be tapered gradually to reduce the risk of
withdrawal symptoms.
Although venlafaxine is a weak inhibitor of CYP2D6, variability has been observed in the pharmacokinetic
parameters of venlafaxine in patients with hepatic or renal function impairment. As a precaution, elderly
patients taking venlafaxine concurrently with a drug that has a narrow therapeutic index and also is
metabolized by CYP2D6 should be carefully monitored. Concurrent use of CYP3A4 inhibitors with venlafaxine
has been shown to interfere with its metabolism and clearance. Similar to the other antidepressants that block
5-HT reuptake, venlafaxine may interact pharmacodynamically to cause toxic levels of 5-HT to accumulate,
leading to the 5-HT syndrome.
Drug interactions
Potentially hazardous interactions with other drugs
Analgesics: increased risk of bleeding with aspirin
and NSAIDs; possibly increased serotonergic effects
with tramadol.
Anti-arrhythmics: risk of ventricular arrhythmias
with amiodarone - avoid.
Antibacterials: risk of ventricular arrhythmias with
erythromycin, moxifloxacin - avoid.
Anticoagulants: effects of warfarin possibly
enhanced; possibly increased risk of bleeding with
dabigatran.
Antidepressants: avoid with MAOIs and
moclobemide (increased risk of toxicity); possibly
enhanced serotonergic effects with duloxetine,
mirtazapine and St John’s wort; possible increased
risk of convulsions with vortioxetine - avoid.
Antimalarials: avoid concomitant use with
artemether/lumefantrine and piperaquine with
artenimol.
Antipsychotics: increases concentration of clozapine
and haloperidol.
Beta-blockers: risk of ventricular arrhythmias with
sotalol - avoid.
Dapoxetine: possible increased risk of serotonergic
effects - avoid.
Dopaminergics: use entacapone with caution;
increased risk of hypertension and CNS excitation
with selegiline - avoid concomitant use.
Methylthioninium: risk of CNS toxicity - avoid if
possible.
Metabolism
Venlafaxine undergoes extensive first-pass
metabolism in the liver mainly to the active
metabolite O-desmethylvenlafaxine; this is mediated
by the cytochrome P450 isoenzyme CYP2D6.
The isoenzyme CYP3A4 is also involved in the
metabolism of venlafaxine. Other metabolites
include N-desmethylvenlafaxine and N,Odidesmethylvenlafaxine. Peak plasma concentrations of
venlafaxine and O-desmethylvenlafaxine occur about 2
and 4 hours after a dose, respectively.
The majority of venlafaxine is excreted in the urine,
mainly in the form of its metabolites, either free or in
conjugated form.
Check Digit Verification of cas no
The CAS Registry Mumber 93413-69-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 9,3,4,1 and 3 respectively; the second part has 2 digits, 6 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 93413-69:
(7*9)+(6*3)+(5*4)+(4*1)+(3*3)+(2*6)+(1*9)=135
135 % 10 = 5
So 93413-69-5 is a valid CAS Registry Number.
InChI:InChI=1/C17H28N2O/c1-18-15-9-7-14(8-10-15)16(13-19(2)3)17(20)11-5-4-6-12-17/h7-10,16,18,20H,4-6,11-13H2,1-3H3
93413-69-5Relevant articles and documents
Room-temperature Pd-catalyzed methoxycarbonylation of terminal alkynes with high branched selectivity enabled by bisphosphine-picolinamide ligand
Chen, Fen-Er,Ke, Miaolin,Liu, Ding,Ning, Yingtang,Ru, Tong
, p. 1041 - 1044 (2022/01/28)
We report the room-temperature Pd-catalyzed methoxy-carbonylation with high branched selectivity using a new class of bisphosphine-picolinamide ligands. Systematic optimization of ligand structures and reaction conditions revealed the significance of both
Amino alcohols using the optically active amino alcohol derivative bi- Nord complex boron - -
-
Paragraph 0064; 0071-0076; 0281-0283; 0285-0286, (2021/04/16)
Disclosed are an amino alcohol-boron-binol complex as an intermediate, including Complex 3-1-1 shown below, and a method for preparing an optically active amino alcohol by using the same, wherein a racemic amino alcohol is resolved in an enationselective manner using a boron compound and a (R)- or (S)-binol, whereby an amino alcohol derivative with high optical purity can be prepared at high yield.
Simple RuCl3-catalyzed N-Methylation of Amines and Transfer Hydrogenation of Nitroarenes using Methanol
Sarki, Naina,Goyal, Vishakha,Tyagi, Nitin Kumar,Puttaswamy,Narani, Anand,Ray, Anjan,Natte, Kishore
, p. 1722 - 1729 (2021/04/19)
Methanol is a potential hydrogen source and C1 synthon, which finds interesting applications in both chemical synthesis and energy technologies. The effective utilization of this simple alcohol in organic synthesis is of central importance and attracts scientific interest. Herein, we report a clean and cost-competitive method with the use of methanol as both C1 synthon and H2 source for selective N-methylation of amines by employing relatively cheap RuCl3.xH2O as a ligand-free catalyst. This readily available catalyst tolerates various amines comprising electron-deficient and electron-donating groups and allows them to transform into corresponding N-methylated products in moderate to excellent yields. In addition, few marketed pharmaceutical agents (e. g., venlafaxine and imipramine) were also successfully synthesized via late-stage functionalization from readily available feedstock chemicals, highlighting synthetic value of this advanced N-methylation reaction. Using this platform, we also attempted tandem reactions with selected nitroarenes to convert them into corresponding N-methylated amines using MeOH under H2-free conditions including transfer hydrogenation of nitroarenes-to-anilines and prepared drug molecules (e. g., benzocaine and butamben) as well as key pharmaceutical intermediates. We further enable one-shot selective and green syntheses of 1-methylbenzimidazole using ortho-phenylenediamine (OPDA) and methanol as coupling partners.
