Levobupivacaine hydrochloride CAS 27262-48-2
Introduction：Basic information about Levobupivacaine hydrochloride CAS 27262-48-2, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Levobupivacaine hydrochloride Basic information
| Product Name: | Levobupivacaine hydrochloride |
| Synonyms: | TIMTEC-BB SBB001337;(S)-(-)-BUPIVACAINE HCL;(S)-(-)-BUPIVACAINE HYDROCHLORIDE;(S)-(-)-1-N-BUTYL-2',6'-DIMETHYL-2-PIPERIDINCARBOXANILID HYDROCHLORIDE;(S)-(-)-1-BUTYL-2-(2,6-XYLYLCARBAMOYL)-PIPERIDINE HYDROCHLORIDE;s-(-)-1-butyl-2',6'-pipecoloxylidide hydrochloride;(s)-1-butyl-2’,6’-piperidinecarboxamidemonohydrochloride;(s)-1-butyl-n-(2,6-dimethylphenyl)-2-piperidinecarboxamidemonohydrochloride |
| CAS: | 27262-48-2 |
| MF: | C18H29ClN2O |
| MW: | 324.89 |
| EINECS: | 1308068-626-2 |
| Product Categories: | API;Inhibitors;Active Pharmaceutical Ingredients;Pharmaceutical Raw Materials;BDO |
| Mol File: | 27262-48-2.mol |
Levobupivacaine hydrochloride Chemical Properties
| Melting point | 254 °C (dec.)(lit.) |
| alpha | -12.5 º (c=2, water) |
| storage temp. | 2-8°C |
| solubility | H2O: soluble20mg/mL, clear |
| form | powder |
| color | white to beige |
| Optical Rotation | [α]/D -10 to -14°, c = 1.0 in H2O |
| Water Solubility | H2O: 20mg/mL, clear |
| InChI | InChI=1/C18H28N2O.ClH/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3;/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21);1H/t16-;/s3 |
| InChIKey | SIEYLFHKZGLBNX-NTISSMGPSA-N |
| SMILES | C([C@@H]1CCCCN1CCCC)(=O)NC1C(=CC=CC=1C)C.Cl |&1:1,r| |
| CAS DataBase Reference | 27262-48-2(CAS DataBase Reference) |
Safety Information
| Hazard Codes | T+,Xn |
| Risk Statements | 26/27/28-20/21/22-28 |
| Safety Statements | 22-36/37/39-45-36/37-53 |
| RIDADR | UN 2811 6.1/PG 2 |
| WGK Germany | 3 |
| RTECS | TK6125000 |
| Description | Levobupivacaine was first launched in the US for the production oflocal anesthesia for surgery and obstetrics and for post-operative pain management. It isthe (S)-enantiomer of the long acting, highly potent local anesthetic bupivacaine(Marcaine) that can be prepared by a three step sequence from (S)-pipecolic acid or from(S)-lysine by oxidative deamination and stereospecific ring closure to (S)-pipecolamidecore structure. Levobupivacaine exhibits its long-acting local anesthetic effect by blockingneuronal sodium channel ion flow in nerve axons. Clinical studies demonstrated anefficacy and a general profile closely resembling those of the racemic bupivacainecurrently in use; however, it produced an enhanced safety profile, in particularsubstantially reduced (about one-third) cardiotoxicity (less effect on myocardial contractilityand QT, prolongation) and CNS depressive side effects. Onset and duration of blockadewere also equivalent or even better. |
| Chemical Properties | white crystalline powder |
| Originator | Chiroscience (UK) |
| Uses | Levobupivacaine hydrochloride has been used as an analyte in tandem mass spectrometry. It may be used to test its inhibitory effect on phosphorylation of extracellular signal-regulated kinase (ERK) mediated by capsaicin It may also be used as a component of poly(D,L-lactide-co-glycolide) (PLGA) microparticles for testing its sustainable release by electrospraying technique. |
| Definition | ChEBI: Levobupivacaine hydrochloride (anhydrous) is the monohydrochloride salt of levobupivacaine. It has a role as a local anaesthetic, an adrenergic antagonist, an amphiphile, an EC 3.1.1.8 (cholinesterase) inhibitor and an EC 3.6.3.8 (Ca(2+)-transporting ATPase) inhibitor. It contains a levobupivacaine(1+). It is an enantiomer of a dextrobupivacaine hydrochloride (anhydrous). |
| Manufacturing Process | Synthesis of L-pipecolic acid 2,6-xylidide (Patent US 4,695,576) 130 g of pipecolic acid and 158.6 g of Laevo (+)-tartaric acid are dissolvedunder stirring in 2 L 95% ethyl alcohol and 125 ml water at 80°C. Thesolution is allowed to cool to room temperature and after two days thecrystallized D-pipecolic-tartrate is separated. The L-pipecolic-tartrate remainsin solution. The filtrate is evaporated and dissolved in 5% acetic acid. Finallythe solution is treated with Amberlite IR 45* in an ion exchanger. The eluatethus obtained is evaporated and the resulting crystalline residue is dried withpotassium hydroxide in vacuo. The product obtained consists of L-pipecolicacid [α]D24 = -26.2°(C = 5, H2O). 4 g of phosphorus pentachloride was added to a suspension of 4 g of Lpipecolic acid hydrochloride in 40 ml acetylchloride. The initial reaction iseffected at a temperature of about 35°C under stirring for 2 hours. Thechlorination is completed by adding during a time period of about 10 minutesan additional two grams of phosphorus pentachloride and stirring over afurther period of 4 hours while maintaining the suspension at a temperatureof about 35°C. The resulting L-pipecolic acid chloride hydrochloride is filteredand washed with toluene and acetone. The crystalline residue is then dried invacuo, m.p. 155°C. A mixture of 2.7 ml 2,6-dimethylaniline, 4 ml acetone, and 4 ml Nmethylpyrrolidone is gradually added under stirring for 2 hours at 70°C to asuspension of 4 g of L-pipecolic acid chloride hydrochloride. This yields acrystalline product, which is filtered, washed with acetone and dried. Thiscrystalline product is then dissolved in water and the base is precipitated bythe addition of ammonia. The base is then extracted by the use of toluene andis recovered by evaporation. The base is recrystallized from a mixture ofhexane and ethanol to yield L-pipecolic acid 2,6-xylidide. The melting point ofthis compound is 129-130°C. Preparation of L-N-n-butylpipecilic acid 2,6-xylidide may de carried out byanalogy with the preparation of L-N-n-propylpipecolic acid 2,6-xylidide (PatentUS 5,777,124). n-Butylbromide and potassium carbonate are added to a solution of L-pipecolicacid 2,6-xylidide dissolved in isopropyl alcohol. Thereafter, 5 ml of water isadded to the mixture and the reaction is carried out for 4 hours at 72°C. To complete the reaction, a further 0.8 ml n-butylbromide are added undercontinuous stirring and heating for 4 hours. The residue is treated with amixture of 250 ml toluene and an equal amount of water at 50°C. The toluenelayer is separated and washed three times with 100 ml warm water (40°C). A175 ml portion of the toluene is removed by evaporation and the remainder isstored at +5°C for 6 hours to achieve crude crystalline L-N-n-butylpipecilicacid 2,6-xylidide. The crystalline product is separated by filtration, washedwith some cooled toluene and dried at 70°C. Recrystallization may be carriedfrom toluene. This product is dissolved in 100 ml ethanol and neutralized withconcentrated hydrochloric acid. Ethanol is removed by evaporation and thehydrochloride product obtained is vacuum dried. Finally the latter isrecrystallized from isopropyl alcohol. |
| Brand name | Chirocaine (Purdue). |
| Therapeutic Function | Local anesthetic |
| Biological Functions | Levobupivacaine hydrochloride (Chirocaine) is theS-enantiomer of bupivacaine. It too has long action.Animal studies show that it has less CNS and cardiactoxicity than does bupivacaine. It also is slightly moremotor sparing than is bupivacaine. |
| General Description | Levobupivacaine belongs to the N-alkyl substituted pipecoloxylidide family and comprises amino-amide group. |
| Biochem/physiol Actions | Levobupivacaine hydrochloride is a sodium channel blocker used as a long-acting local anaesthetic for epidural anesthesia. Levobupivacaine is the (S)-isomer of bupivacaine, with efficacy similar to that of bupivacaine with a reduced risk of cardiotoxicity. |
| Mode of action | Levobupivacaine Hydrochloride is the hydrochloride salt of levobupivacaine, an amide derivative with anesthetic property. Levobupivacaine reversibly binds voltage-gated sodium channels to modulate ionic flux and prevent the initiation and transmission of nerve impulses (stabilizing neuronal membrane), thereby resulting in analgesia and anesthesia. In comparison with racemic bupivacaine, levobupivacaine is associated with less vasodilation and has a longer duration of action. |
Levobupivacaine hydrochloride Preparation Products And Raw materials
| Raw materials | L(+)-Tartaric acid-->Phosphorus pentachloride-->DL-Pipecolinic acid-->AMBERLITE-->1-Bromobutane-->4-Bromo-2,6-dimethylaniline |
