71320-77-9 Usage
Description
Different sources of media describe the Description of 71320-77-9 differently. You can refer to the following data:
1. Moclobemide is the first of a new generation of non-hydrazine, reversible MAO-A
inhibitors useful in the treatment of depression. Moclobemide is a selective
inhibitor of MAO-A, allowing tyramine to be metabolized by MAO-B. In controlled
studies, moclobemide was clinically superior to desipramine and showed no
cholinergic or cardiovascular side-effects. A metabolite is currently under
investigation for treatment of Parkinson’s disease,.
2. Moclobemide (Item No. 24361) is an analytical reference standard categorized as an antidepressant. This product is intended for research and forensic applications.
Chemical Properties
White to Off-White Solid
Originator
Hoffmann-LaRoche (Switzerland)
Uses
Different sources of media describe the Uses of 71320-77-9 differently. You can refer to the following data:
1. A reversible monoamine oxidase inhibitor
2. Antidepressant;Mono amine oxidase
inhibitor (Type A)
3. A reversible monoamine oxidase inhibitor.
Definition
ChEBI: A member of the class of benzamides that is benzamide substituted by a chloro group at position 4 and a 2-(morpholin-4-yl)ethyl group at the nitrogen atom. It acts as a reversible monoamine oxidase inhibitor and is used in the treatment of depression.
Brand name
Aurorix
Biochem/physiol Actions
Moclobemide is a reversible monoamine oxidase A inhibitor (MAOI); antidepressant. Elimination half-life in humans = 1 -3 hrs; absolute oral bioavailability. Unlike other MAO inhibitors, does not significantly increase blood pressure in humans upon combination with tyramine.
Mechanism of action
Moclobemide is an RIMA that preferentially inhibits MAO-A (~80%) and, to a lesser extent, MAO-B (20–30%
inhibition), thereby increasing the concentration of 5-HT, NE, and other catecholamines in the synaptic cleft
and in storage sites. During chronic therapy with the MAOIs, adaptive changes at the noradrenergic and
serotonergic receptors occur (“downregulation”) as a result of neurotransmitter hypersensitivity because of
prolonged concentrations of NE and 5-HT at the postsynaptic receptor. This mechanism is likely the basis for its antidepressant activity. Inhibition
of MAO-A by moclobemide is short-acting (maximum, 24 hours) and reversible. This is in contrast to
phenelzine, which is nonselective, long-acting, and irreversible in its binding to MAO-A and MAO-B.
The pharmacokinetics for moclobemide are linear only up to 200 mg; at higher doses, nonlinear
pharmacokinetics are observed. Although well absorbed from the GI tract, the presence of food reduces
the rate but not the extent of absorption of moclobemide. Small quantities of moclobemide are distributed into
human breast milk. Moclobemide undergoes a complex metabolism, initially involving morpholine carbon and
nitrogen oxidation, deamination, and aromatic hydroxylation. The N-oxide and ring-opened metabolites retain
some in vitro MAO-A inhibition. Moclobemide is a weak inhibitor of CYP2D6 in vitro. It is extensively
metabolized in the liver by oxidation and is eliminated primarily into the urine as conjugates. Less than 1% of
an administered dose of moclobemide is eliminated unmetabolized.
Because moclobemide is partially metabolized by the polymorphic isozymes CYP2C19 and CYP2D6, plasma
concentrations of moclobenmide may be affected in patients who are poor metabolizers. In patients who are
slow metabolizers, the AUC for moclobemide was 1.5 times greater than the AUC in patients who are extensive metabolizers and receiving the same dose. This increase is within the normal range of variation (up to twofold) typically seen in patients.
Clinical Use
Reversible MAOI:
Depression
Social phobia
Drug interactions
Drug interactions for the RIMAs include interaction with SSRI antidepressants, which can cause the 5-HT
syndrome. The effect of stimulant drugs, such as methylphenidate and
dextroamphetamine (used to treat ADHD), may be increased. Some over-the-counter cold and hay fever
decongestants (i.e., sympathomimetic amines) can have increased stimulant effects. Selegiline, a selective
MAO-B used for Parkinson's disease, should not be used concurrently with the RIMAs. Unlike the irreversible
MAOIs, no significant interactions with foods occur, because the selective inhibition of MAO-A does not stop
the metabolism of tyramine. The RIMAs must not be taken concurrently with a nonreversible MAOI.
Metabolism
Moclobemide is extensively metabolised in the liver, partly
by the cytochrome P450 isoenzymes CYP2C19 and
CYP2D6.
Metabolites of moclobemide and a small amount of
unchanged drug are excreted in the urine
references
[1] pisani l, barletta m, soto-otero r, nicolotti o, mendez-alvarez e, catto m, introcaso a, stefanachi a, cellamare s, altomare c, carotti a. discovery, biological evaluation, and structure-activity and -selectivity relationships of 6'-substituted (e)-2-(benzofuran-3(2h)-ylidene)-n-methylacetamides, a novel class of potent and selective monoamine oxidase inhibitors. j med chem. 2013 mar 28;56(6):2651-64. [2] nair np, ahmed sk, kin nm. biochemistry and pharmacology of reversible inhibitors of mao-a agents: focus on moclobemide. j psychiatry neurosci. 1993 nov;18(5):214-25.
Check Digit Verification of cas no
The CAS Registry Mumber 71320-77-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,1,3,2 and 0 respectively; the second part has 2 digits, 7 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 71320-77:
(7*7)+(6*1)+(5*3)+(4*2)+(3*0)+(2*7)+(1*7)=99
99 % 10 = 9
So 71320-77-9 is a valid CAS Registry Number.
InChI:InChI=1/C13H17ClN2O2/c14-12-3-1-11(2-4-12)13(17)15-5-6-16-7-9-18-10-8-16/h1-4H,5-10H2,(H,15,17)
71320-77-9Relevant articles and documents
Biocatalytic Synthesis of Moclobemide Using the Amide Bond Synthetase McbA Coupled with an ATP Recycling System
Fairlamb, Ian J. S.,Grogan, Gideon,Lloyd, Richard C.,Petchey, Mark R.,Rowlinson, Benjamin
, p. 4659 - 4663 (2020)
The biocatalytic synthesis of amides from carboxylic acids and primary amines in aqueous media can be achieved using the ATP-dependent amide bond synthetase McbA, via an adenylate intermediate, using only 1.5 equiv of the amine nucleophile. Following earlier studies that characterized the broad carboxylic acid specificity of McbA, we now show that, in addition to the natural amine substrate 2-phenylethylamine, a range of simple aliphatic amines, including methylamine, butylamine, and hexylamine, and propargylamine are coupled efficiently to the native carboxylic acid substrate 1-acetyl-9H-β-carboline-3-carboxylic acid by the enzyme, to give amide products with up to >99% conversion. The structure of wild-type McbA in its amidation conformation, coupled with modeling and mutational studies, reveal an amine access tunnel and a possible role for residue D201 in amine activation. Amide couplings were slower with anilines and alicyclic secondary amines such as pyrrolidine and piperidine. The broader substrate specificity of McbA was exploited in the synthesis of the monoamine oxidase A inhibitor moclobemide, through the reaction of 4-chlorobenzoic acid with 1.5 equiv of 4-(2-aminoethyl)morpholine, and utilizing polyphosphate kinases SmPPK and AjPPK in the presence of polyphosphoric acid and 0.1 equiv of ATP, required for recycling of the cofactor.
Amide Bond Formation via the Rearrangement of Nitrile Imines Derived from N-2-Nitrophenyl Hydrazonyl Bromides
Boyle, Mhairi,Livingstone, Keith,Henry, Martyn C.,Elwood, Jessica M. L.,Lopez-Fernandez, J. Daniel,Jamieson, Craig
supporting information, p. 334 - 338 (2022/01/20)
We report how the rearrangement of highly reactive nitrile imines derived from N-2-nitrophenyl hydrazonyl bromides can be harnessed for the facile construction of amide bonds. This amidation reaction was found to be widely applicable to the synthesis of primary, secondary, and tertiary amides and was used as the key step in the synthesis of the lipid-lowering agent bezafibrate. The orthogonality and functional group tolerance of this approach was exemplified by the N-acylation of unprotected amino acids.
N -Heterocyclic carbene (NHC) catalyzed amidation of aldehydes with amines via the tandem N -hydroxysuccinimide ester formation
Singh, Ashmita,Narula
supporting information, p. 7486 - 7490 (2021/05/13)
A facile method for the amidation of aldehydes by a cascade approach was developed. This methodology, reported for the first time, uses a N-heterocyclic carbene (NHC) as the catalyst, and N-hydroxysuccinimide (NHS) mediated synthesis of amides utilising TBHP as the oxidant. Various substituted aldehydes reacted smoothly with NHS giving the corresponding active esters in moderate to good yields, which facilely converted into amides in one pot. In addition, the drug moclobemide was synthesized to represent the practical utility of the developed methodology. This journal is
Cobalt catalysed aminocarbonylation of thiols in batch and flow for the preparation of amides
Domínguez, Gema,Ordu?a, Jose Maria,Pérez-Castells, Javier
, p. 30398 - 30406 (2021/10/20)
The synthesis of amides from thiols through a cobalt-catalyzed aminocarbonylation is shown. After optimizing all the reaction parameters, the methodology makes possible the obtention of amides with variable yields, while competing reactions such as the formation of disulfides and ureas can be limited. The process works well with aromatic thiols with electron donating groups (EDG) whereas other thiols give reaction with lower yields. The previous process has been transferred and optimized into flow equipment, thus allowing using less CO in a safer way, and permitting the scaling up of the synthesis. Two drugs, moclobemide and itopride were prepared with this methodology, albeit only in the second case with good results. A mechanistic pathway is proposed.
