CAS 138112-76-2 Agomelatine (HCID 82148)

개요

Agomelatine is a member of acetamides.

이름 및 식별자

우선 이름: Agomelatine
IUPAC: N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide
영어명: Agomelatine
분자식: C15H17NO2
분자량: 243.3

이름 및 동의어

Agomelatine138112-76-2ThymanaxValdoxanS20098S-20098AgomelatinaAGO-178S 20098N-(2-(7-methoxy-1-naphthyl)ethyl)acetamideagomelatinumAGO178

이름 더 보기

AGOMELATINGOMELATINEMELITORAgomelatine original crystal formomeLatineAgomeLMelitorCS-1963

DTXSID3057642137R1N49ADN-[2-(7-methoxy-1-naphthyl)ethyl]acetamideDTXCID4031431RefChem:110192N06AX22N-(2-(7-Methoxynaphthalen-1-yl)ethyl)acetamideN-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide

데이터베이스 식별자

CAS: 138112-76-2
PubChem CID: 82148
DTXSID: DTXSID3057642
ChEMBL: CHEMBL10878
ChEBI: CHEBI:134990
UNII: 137R1N49AD
EC Number: 629-727-7
Nikkaji: J481.046E

물성

구조 계산 물성

XLogP: 2.7
극성 표면적: 38.3 Å²
수소 결합 공여자 수: 1
수소 결합 수용자 수: 2
회전 가능 결합 수: 4
무거운 원자 수: 18
형식 전하: 0
복잡도: 280

실험 및 물리화학적 성질

Drugs · 3건

Pharmaceuticals

Pharmaceuticals -> Antidepressants

Pharmaceuticals -> Listed in ZINC15

Solubility · 2건

~0.5 mg/ml in 1:1 EtOH:PBS (pH 7.2); ~30 mg/ml in EtOH, DMF & DMSO

7.76e-03 g/L

Human Drugs · 2건

Breast Feeding; Lactation; Milk, Human; Antidepressants

EMA approved medicines: Human medicine

Physical DescriptionSolid

Collision Cross Section156.3 Å² [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

물리화학적 성질

녹는점: 107 · 107-109°C
끓는 점: 478.8 · 478.8±28.0 °C(Predicted)
밀도: 1.109 · 1.109±0.06 g/cm3(Predicted)
저장 조건: 2 · 2-8°C
용해도: 50 mg/mL · DMSO: >50mg/mL
물리적 상태: 가루
산도 계수 (pKa): 16.17 · 16.17±0.46(Predicted)
색상: 흰색에서 황백색까지
Merck: 14 · 14,190
InChI: InChI=1S/C15H17NO2/c1-11(17)16-9-8-13-5-3-4-12-6-7-14(18-2)10-15(12)13/h3-7,10H,8-9H2,1-2H3,(H,16,17)
InChIKey: YJYPHIXNFHFHND-UHFFFAOYSA-N
SMILES: C(NCCC1=C2C(C=CC(OC)=C2)=CC=C1)(=O)C

화학적 성질

White Solid

안전 및 규제

GHS 분류

GHS Classification · 5건

This chemical does not meet GHS hazard criteria for 1.9% (1 of 54) of reports.

Warning

H315 (22.2%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P273, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 54 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

유해성 정보

Hazard Classes and CategoriesSkin Irrit. 2 (22.2%)

독성 정보

Effects During Pregnancy and Lactation◉ Summary of Use during Lactation

안전 데이터

wgk: 3
rtecs: AC5956323
ridadr: UN 3077 9 / PGIII
독성: mouse,LD50,oral,> 1gm/kg (1000mg/kg),United States Patent Document. Vol. #5318994,
HS 번호: 29241990
risk_code: 50
hazard_code: N
safety_code: 61
Hazard Classifications: Aquatic Acute 1Aquatic Chronic 1
스토리지 클래스: 11 - Combustible Solids

화학 및 산업

약리 정보

ATC Code · 3건

N06AX22

N - Nervous system

QN - Nervous system

Protein Binding> 95%

Pharmacodynamics · 1건

Agomelatine resynchronises circadian rhythms in animal models of delayed sleep phase syndrome and other circadian rhythm disruptions. It increases noradrenaline and dopamine release specifically in the frontal cortex and has no influence on the extracellular levels of serotonin. Agomelatine has shown an antidepressant-like effect in animal depression models, (learned helplessness test, despair test, and chronic mild stress) circadian rhythm desynchronisation, and in stress and anxiety models. In humans, agomelatine has positive phase shifting properties; it induces a phase advance of sleep, body temperature decline and melatonin onset. Controlled studies in humans have shown that agomelatine is as effective as the SSRI antidepressants paroxetine and sertraline in the treatment of major depression

Mechanism of ActionThe novel antidepressant agent, agomelatine, behaves as an agonist at melatonin receptors (MT1 and MT2) and as an antagonist at serotonin (5-HT)(2C) receptors.

Biological Half-Life<2 hours

Metabolism/MetabolitesHepatic (90% CYP1A2 and 10% CYP2C9).

용도 및 제조

UsesUse (kg; approx.) in Germany (2009): >100

응용 분야 · 2건

개요Agomelatine 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.

용도Agomelatine 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.