Agomelatine

Base Information

• Chemical Name: Agomelatine
• CAS No.: 138112-76-2
• Molecular Formula: C15H17NO2
• Molecular Weight: 243.305
• Hs Code.: 29241990
• European Community (EC) Number: 629-727-7
• UNII: 137R1N49AD
• DSSTox Substance ID: DTXSID3057642
• Nikkaji Number: J481.046E
• Wikipedia: Agomelatine
• Wikidata: Q395229
• NCI Thesaurus Code: C72684
• Pharos Ligand ID: 6PRP7G76BZ6N
• Metabolomics Workbench ID: 43671
• ChEMBL ID: CHEMBL10878
• Mol file: 138112-76-2.mol

Synonyms:AGO 178;AGO-178;AGO178;agomelatine;N-(2-(7-methoxy-1-naphthyl)ethyl)acetamide;S 20098;S-20098;S20098;thymanax;valdoxan

Chemical Property of Agomelatine

Chemical Property:

• Appearance/Colour: white solid
• Melting Point: 107-109 °C
• Boiling Point: 478.8 °C at 760 mmHg
• PKA: 16.17±0.46(Predicted)
• Flash Point: 243.4 °C
• PSA: 38.33000
• Density: 1.109 g/cm³
• LogP: 2.91790
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: >50mg/mL
• XLogP3: 2.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 4
• Exact Mass: 243.125928785
• Heavy Atom Count: 18
• Complexity: 280

Purity/Quality:

99% min ^*data from raw suppliers

Agomelatine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): N
• Hazard Codes: N
• Statements: 50
• Safety Statements: 61

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CC(=O)NCCC1=CC=CC2=C1C=C(C=C2)OC
• Recent ClinicalTrials: A Study on the Efficacy of Agomelatine Combined With Antipsychotics to Treat Negative Symptoms in Schizophrenia
• Recent EU Clinical Trials: Efficacy and safety of 2 doses of agomelatine (10mg, 25mg) given orally in children (from 7 to less than 12 years) and adolescents (from 12 to less than 18 years) with moderate to severe Major Depressive Disorder.
• Uses: Melatonin drugs. Agomelatine is an antidepressant drug. It is classified as a norepinephrine-dopamine disinhibitor (NDDI) due to its antagonism of the 5-HT2C receptor. Activation of 5-HT2C receptors by serotonin inhibits dopamine and norepinephrine release. Antagonism of Agomelatine is a melatoninergic agonist and selective antagonist of 5-HT2C receptors, and has been shown to be active in several animal models of depression. Agomelatine (S20098) displayed pKi values of 6.4 and 6.2 at native (porcine) and cloned, human (h)5-hydroxytryptamine (5-HT)2C receptors, respectively. Agomelatine has been used: to study its effects on adult neurogenesis and hippocampus apoptosis using the stress-induced depression model of rats to explore its effects on tau protein phosphorylation and to study its neuroprotective mechanism to study its effects on intracellular calcium ([Ca2+]i) signaling in peripheral neurons of rat dorsal root ganglion (DRG) neurons
• Description: Agomelatine is an agonist of melatonin (MT) receptors and a derivative of melatonin . It binds to MT1 and MT2 receptors (Kis = 0.14 and 0.41 nM, respectively) and has an EC50 value of 0.1 nM in a [35S]GTPγS binding assay using CHO cells expressing MT2 receptors. Agomelatine is also an antagonist of the serotonin (5-HT) receptor subtypes 5-HT2B and 5-HT2C (Kis = 0.26 and 0.71 nM, respectively, for the human receptors). Agomelatine (40 mg/kg) inhibits the penile erection response induced by the 5-HT2 agonist Ro 60-0175 in rats. It also increases extracellular levels of noradrenaline and dopamine in the frontal cortex of freely moving rats when administered at doses ranging from 20 to 80 mg/kg. Agomelatine (10 mg/kg) reduces immobility time in the forced swim test and increases the amount of time spent in the open arms of the elevated plus maze in mice, indicating antidepressant-like and anxiolytic-like activity, in a transgenic neuroendocrine model of depression. It also increases the rate of readjustment to circadian activity cycles following an induced phase shift.
• Clinical Use: Antidepressant
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: avoid with ciprofloxacin. Antidepressants: metabolism inhibited by fluvoxamine. Antimalarials: avoid with artemether with lumefantrine and artenimol with piperaquine.

Technology Process of Agomelatine

There total 127 articles about Agomelatine 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: 99.5%

2-(7-methoxynaphthalen-1-yl)ethanamine hydrochloride (139525-77-2) + acetic anhydride (108-24-7) → agomelatine (138112-76-2)

Guidance literature:

With sodium acetate; In ethanol; for 1h; Reflux;

DOI:10.1002/ejoc.201402886

Reference yield: 98.0%

N,N-dibenzyl-2-(7-methoxynaphthalen-1-yl)ethanamine + acetic anhydride (108-24-7) → agomelatine (138112-76-2)

Guidance literature:

N,N-dibenzyl-2-(7-methoxynaphthalen-1-yl)ethanamine; With 20% palladium hydroxide-activated charcoal; hydrogen; In ethanol; water; ethyl acetate; for 30h; under 3750.38 Torr; Autoclave;

acetic anhydride; With sodium acetate; for 4h;

Reference yield: 97.5%

2-(7-methoxynaphth-1-yl)ethylamine (138113-09-4) + acetic anhydride (108-24-7) → agomelatine (138112-76-2)

Guidance literature:

In tetrahydrofuran; at 0 - 20 ℃; for 6h; Concentration; Temperature;

upstream raw materials:

2-(7-methoxynaphthalen-1-yl)ethanamine hydrochloride

acetyl chloride

2-(7-methoxynaphth-1-yl)ethylamine

2-(7-methoxynaphthalen-1-yl)acetic acid

Downstream raw materials:

2-(7-methoxynaphth-1-yl)ethylamine

N-[2-(7-Hydroxy-1-naphthyl)ethyl]-acetamide

C₁₇H₁₉NO₃

Refernces

• 1、 Kandagatla, Bhaskar,Raju, Vetukuri Venkata Naga Kali Vara Prasada,Reddy, Ganta Madhusudhan,Rao, Sirigiri Chandrakanth,Iqbal, Javed,Bandichhor, Rakeshwar,Oruganti, Srinivas. "A facile synthesis of melatonergic antidepressant agomelatine". . p. 7125 - 7127. Retrieved 2012.
• 2、 Yous,Andrieux,Howell,Morgan,Renard,Pfeiffer,Lesieur,Guardiola-Lemaitre. "Novel naphthalenic ligands with high affinity for the melatonin receptor". . p. 1484 - 1486. Retrieved 1992.
• 3、 Markl, Christian,Zlotos, Darius P.. "A novel synthesis of the antidepressant agomelatine". . p. 79 - 82. Retrieved 2011.
• 4、 Depreux,Lesieur,Mansour,Morgan,Howell,Renard,Caignard,Pfeiffer,Delagrange,Guardiola,Yous,Demarque,Adam,Andrieux. "Synthesis and structure-activity relationships of novel naphthalenic and bioisosteric related amidic derivatives as melatonin receptor ligands". . p. 3231 - 3239. Retrieved 1994.
• 5、 -. "Preparation method of agomelatine". Paragraph 0039; 0043; 0051-0055; 0061-0065; 0071-0074. . Retrieved 2018/09/11.
• 6、 -. "Preparation method of agomelatine". Paragraph 0018; 0022; 0026. . Retrieved 2018/01/12.