Etomidate CAS 33125-97-2
Introduction：Basic information about Etomidate CAS 33125-97-2, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Etomidate Basic information
| Product Name: | Etomidate |
| Synonyms: | (r)-(+)-1-(alpha-methylbenzyl)imidazole-5-carboxylicacidethylester;1-(1-phenylethyl)-,ethylester,(r)-1h-imidazole-5-carboxylicaci;1-(1-Phenylethyl)-1H-imidazole-5-carboxylic acid ethyl ester;1-(1-phenylethyl)-1h-imidazole-5-carboxylicacidethylester;Amidate, R16659;Imidazole-5-carboxylic acid, 1-(alpha-methylbenzyl)-, ethyl ester, (R)-(+);1-[(R)-α-Methylbenzyl]-1H-imidazole-5-carboxylic acid ethyl ester;Etomidate (200 mg) |
| CAS: | 33125-97-2 |
| MF: | C14H16N2O2 |
| MW: | 244.29 |
| EINECS: | 251-385-9 |
| Product Categories: | EVISTA;Other APIs;GABA;GABA/Glycine receptor;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;chiral;Aromatics Compounds;Aromatics;Intermediate;API;pharmaceutical;33125-97-2 |
| Mol File: | 33125-97-2.mol |
Etomidate Chemical Properties
| Melting point | 72-74°C |
| alpha | D20 +66° (c = 1 in ethanol) |
| Boiling point | 160-162 °C(Press: 1 Torr) |
| density | 1.11±0.1 g/cm3(Predicted) |
| storage temp. | 2-8°C |
| solubility | DMSO: >10 mg/mL |
| pka | pKa 4.24(H2O t=25.0) (Uncertain) |
| form | powder |
| color | white |
| Merck | 14,3881 |
| InChI | 1S/C14H16N2O2/c1-3-18-14(17)13-9-15-10-16(13)11(2)12-7-5-4-6-8-12/h4-11H,3H2,1-2H3/t11-/m1/s1 |
| InChIKey | NPUKDXXFDDZOKR-LLVKDONJSA-N |
| SMILES | CCOC(=O)c1cncn1[C@H](C)c2ccccc2 |
| CAS DataBase Reference | 33125-97-2(CAS DataBase Reference) |
| NIST Chemistry Reference | Etomidate(33125-97-2) |
Safety Information
| Hazard Codes | Xn |
| Risk Statements | 22 |
| Safety Statements | 36 |
| RIDADR | UN 3077 9 / PGIII |
| WGK Germany | 3 |
| RTECS | NI4021500 |
| HazardClass | 9 |
| PackingGroup | III |
| HS Code | 29332900 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Acute Tox. 4 Oral Aquatic Acute 1 Aquatic Chronic 1 |
| Toxicity | LD50 in mice, rats (mg/kg): 29.5, 14.8-24.3 i.v. (Janssen) |
| Description | Etomidate , ethyl (R)-(+)-1(α-methylbenzyl)-imidazole-5-carboxylate, Mr224.28, is a white to yellowish crystalline oramorphous powder. It is insolublein water at pH 7, but soluble in acidicaqueous solutions at pH<3. Etomidate is solublein propylene glycol and readily soluble inalcohol. |
| Chemical Properties | Etomidate is a white crystalline powder. easily soluble in water, methanol, ethanol and propylene glycol, soluble in chloroform, insoluble in acetone, insoluble in ether. Its effects on the central nervous system is similar to barbiturates. |
| Originator | Hypnomidate,Janssen,W. Germany,1977 |
| Uses | Etomidate is a GABAA receptors agonist with short-acting sedative, hypnotic, and general anesthetic properties. It is a unique drug used for induction of general anesthesia and sedation. It is also a hypnotic. Hypnotic effect of Etomidate is strong , and its efficacy is about 12 times higher than thiopental, it has no analgesic effect. |
| Definition | ChEBI: Etomidate is the ethyl ester of 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. It is an intravenous general anaesthetic with no analgesic activity. It has a role as an intravenous anaesthetic and a sedative. It is a member of imidazoles and an ethyl ester. It derives from a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. |
| Indications | Etomidate is administered intravenously asa short-acting anesthetic for the induction oflengthy anesthesia, especially for the inductionof neuroleptanalgesia and inhalationanesthesia . Etomidate produces3 – 5 min of sleep. |
| Brand name | Amidate (Hospira);Hypnomidate concentrate;Hypnomidate injection;Hypromidate;Nalgol;Sibu. |
| Therapeutic Function | Hypnotic |
| World Health Organization (WHO) | Etomidate, a potent hypnotic agent, was introduced in 1977 foruse as an intravenous anaesthetic. Its prolonged use can inhibit adrenalsteroidogenesis and, following reports of reduced serum cortisol levelsunresponsive to ACTH injection, the manufacturer suspended promotion ofetomidate for sedation in intensive care in 1983. In 1985 regulatory action takenonly in the United Kingdom further restricted use of the drug to induction ofanaesthesia. Etomidate remains widely available and is currently registered forinduction of anaesthesia in 34 countries and for maintenance of anaesthesia in 17countries. It has never been registered for sedation. |
| Biological Functions | The pharmacological properties of etomidate (Amidate)are similar to those of the barbiturates, although its usemay provide a greater margin of safety because of itslimited effects on the cardiovascular and respiratorysystems. Since it has a relatively short elimination halflife(t1/2β = 2.9 hours), in addition to its use as an induction agent, etomidate has been used as a supplement tomaintain anesthesia in some critically ill patients.Etomidate is rapidly hydrolyzed in the liver. |
| General Description | Etomidate is a carboxylated imidazole intended for the inductionof general anesthesia. It is marketed as the morepotent R (+) isomer. It is believed to exert its anestheticeffect via positive modulation of the GABAA receptor. Itis not water soluble and is available in the United States as a2-mg/mL solution containing 35% v/v propylene glycol andin Europe as a soybean oil and medium-chain triglyceridesformulation. The propylene glycol has been associatedwith moderate-to-severe pain on injection and irritation ofthe vascular tissue. A high incidence of skeletal musclemovements were noted in about 32% of patients followingetomidate injection. Case reports of seizures are also foundin the literature. |
| Biological Activity | Etomidate is a general anesthetic with GABA modulatory and GABA-mimetic actions; selectively interacts with β 2- and β 3-subunit containing GABAA receptors. Short acting and potent hypnotic, with low toxicity.The possible neuroprotective effect of etomidate against streptozotocin-induced (STZ-induced) hyperglycaemia were investigated in the rat brain and spinal cord. Etomidate treatment demonstrated neuroprotective effect on the neuronal tissue against the diabetic oxidative damage. |
| Clinical Use | Etomidate should only beused for induction of anesthesia when the cardiac benefitsoutweigh the risks associated with adrenal insufficiency.Etomidate is quickly distributed throughout most organsin the body after intravenous administration and the tissueconcentrations equal and sometimes exceed the plasmaconcentrations. The lipid solubility of the drug allows it torapidly penetrate into the brain with peak concentrationsoccurring within 1 minute of administration. Etomidate israpidly metabolized in the plasma and liver via esterases.About 75% of the drug is eliminated in the urine as the inactiveester hydrolyzed carboxylic acid. |
| Side effects | Etomidate may cause pain on injection and may producemyoclonic muscle movements in approximately40% of patients during its use as an induction anesthetic.In addition, etomidate can suppress the adrenocorticalresponse to stress, an effect that may last up to 10 hours. |
| Synthesis | The preparation of etomidate involvesa modification of Jones’ synthesis: α-phenylethylamine is alkylated with ethyl chloroacetateto the N-(α-phenylethyl)-glycine ester,whose NH group is formylated. This productis condensed with methyl formate and cyclized withHCl-KSCNto yield ethyl 2-mercapto-1-(α-methylbenzyl)-5-imidazolecarboxylate, whichis then oxidatively desulfurized . The (R)isomer is obtained by separating the racemicacid with (R)-(+)-1-phenylethylamine. |
| Veterinary Drugs and Treatments | Etomidate may be useful as an alternative to thiopental or propofolfor anesthetic induction in small animals, particularly in patientswith preexisting cardiac dysfunction, head trauma, or that are criticallyill. |
| Drug interactions | Potentially hazardous interactions with other drugs Adrenergic neurone blockers: enhanced hypotensive effect. Antihypertensives: enhanced hypotensive effect. Antidepressants: avoid MAOIs for 2 weeks before surgery; increased risk of arrhythmias and hypotension with tricyclics. Antipsychotics: enhanced hypotensive effect. |
| Metabolism | Etomidate is hydrolyzed by hepatic esterases to the corresponding inactive carboxylic acid, with subsequent renal and biliary excretion terminating its action. Its apparent elimination half-life is approximately 5 to 6 hours, with a volume of distribution of 5 to 7 L/kg. Changes in hepatic blood flow or hepatic metabolism will have only moderate effects on etomidate disposition. Concerns regarding the ability of etomidate to precipitate myoclonic jerks and inhibit adrenal steroid synthesis have been reported. |
| storage | Room temperature |
| Mode of action | The exact mechanism of action of etomidate is unknown. It is felt to induce sedation by interaction with GABA receptors. and likely enhances the activity of a-aminobutyric acid. However, it is not structurally related to benzodiazepines or to barbiturates. Of significantnote, etomidate exhibits no analgesic properties. |
Etomidate Preparation Products And Raw materials
| Raw materials | N,N-Dimethylformamide-->Ethyl chloroacetate-->FORMIC ACID SODIUM-->Nitric acid-->thiocyanate-->DL-ALPHA-METHYLBENZYLAMINE-->Potassium Citrate-->Formic acid |
