(2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide

• ChemBase ID: 875
• Molecular Formular: C18H28N2O
• Molecular Mass: 288.42772
• Monoisotopic Mass: 288.22016353
• SMILES: O=C(Nc1c(cccc1C)C)[C@H]1N(CCCC1)CCCC
• Canonical SMILES: CCCCN1CCCC[C@H]1C(=O)Nc1c(C)cccc1C
• InChI: InChI=1S/C18H28N2O/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)/t16-/m0/s1
• InChIKey: LEBVLXFERQHONN-INIZCTEOSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
• IUPAC Traditional name: (-)-bupivacaine; levobupivacaine
• Brand Name: Chirocaine
• Synonyms: (2S)-1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide; L-(-)-Bupivacaine; Levobupivacaine; (S)-(-)-Bupivacaine; Levobupivacaine

Database IDs

• CAS Number: 27262-47-1
• PubChem SID: 46505295; 160964338
• PubChem CID: 92253

CALCULATED PROPERTIES

JChem

• Acid pKa: 13.623539
• H Acceptors: 2
• H Donor: 1
• LogD (pH = 5.5): 2.0522962
• LogD (pH = 7.4): 3.8159845
• Log P: 4.5155187
• Molar Refractivity: 90.1933 cm^3
• Polarizability: 34.286346 Å^3
• Polar Surface Area: 32.34 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.31
• LOG S: -3.47
• Solubility (Water): 9.77e-02 g/l

PROPERTIES

Physical Property

• Solubility: Methanol
• Apperance: White Solid
• Melting Point: 136-137°C
• Hydrophobicity(logP): 3.6

Safety Information

• Storage Condition: Refrigerator

DETAILS

DrugBank - DB01002

• Drug Groups: approved
• Description: Levobupivacaine is an amino-amide local anaesthetic drug belonging to the family of n-alkylsubstituted; pipecoloxylidide. It is the S-enantiomer of bupivacaine. Levobupivacaine hydrochloride is commonly marketed by AstraZeneca under the trade name Chirocaine. Compared to bupivacaine, levobupivacaine is associated with less vasodilation and has a longer duration of action. It is approximately 13 per cent less potent (by molarity) than racemic bupivacaine.Levobupivacaine is indicated for local anaesthesia including infiltration, nerve block, ophthalmic, epidural and intrathecal anaesthesia in adults; and infiltration analgesia in children. Adverse drug reactions (ADRs) are rare when it is administered correctly. Most ADRs relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, however allergic reactions can rarely occur. [Wikipedia]
• Indication: For the production of local or regional anesthesia for surgery and obstetrics, and for post-operative pain management
• Pharmacology: Levobupivacaine, a local anesthetic agent, is indicated for the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.
• Toxicity: LD50: 5.1mg/kg in rabbit, intravenous; 18mg/kg in rabbit, oral; 207mg/kg in rabbit, parenteral; 63mg/kg in rat, subcutaneous (Archives Internationales de Pharmacodynamie et de Therapie. Vol. 200, Pg. 359, 1972.) Levobupivacaine appears to cause less myocardial depression than both bupivacaine and ropivacaine, despite being in higher concentrations.
• Affected Organisms: Humans and other mammals
• Biotransformation: Levobupivacaine is extensively metabolized with no unchanged levobupivacaine detected in urine or feces. In vitro studies using [14 C] levobupivacaine showed that CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine to desbutyl levobupivacaine and 3-hydroxy levobupivacaine, respectively. In vivo, the 3-hydroxy levobupivacaine appears to undergo further transformation to glucuronide and sulfate conjugates. Metabolic inversion of levobupivacaine to R(+)-bupivacaine was not evident both in vitro and in vivo.
• Absorption: The plasma concentration of levobupivacaine following therapeutic administration depends on dose and also on route of administration, because absorption from the site of administration is affected by the vascularity of the tissue. Peak levels in blood were reached approximately 30 minutes after epidural administration, and doses up to 150 mg resulted in mean C_max levels of up to 1.2 μg/mL.
• Half Life: 3.3 hours
• Protein Binding: >97%
• Elimination: Following intravenous administration, recovery of the radiolabelled dose of levobupivacaine was essentially quantitative with a mean total of about 95% being recovered in urine and feces in 48 hours. Of this 95%, about 71% was in urine while 24% was in feces.
• Distribution: 66.91 ±18.23 L [after intravenous administration of 40 mg in healthy volunteers]
• Clearance: 39.06 ±13.29 L/h [after intravenous administration of 40 mg in healthy volunteers]
• References: Leone S, Di Cianni S, Casati A, Fanelli G: Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine. Acta Biomed. 2008 Aug;79(2):92-105. [Pubmed] ; "http://www.orgyn.com/resources/genrx/D003445.asp":http://www.orgyn.com/resources/genrx/D003445.asp; Burlacu CL, Buggy DJ: Update on local anesthetics: focus on levobupivacaine. Ther Clin Risk Manag. 2008 Apr;4(2):381-92. [Pubmed]
• External Links: Wikipedia; RxList

Toronto Research Chemicals - B689546

Local anaesthetic used for epidural and intrathecal anaesthesia.

REFERENCES

• Leone S, Di Cianni S, Casati A, Fanelli G: Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine. Acta Biomed. 2008 Aug;79(2):92-105. Pubmed
• Burlacu CL, Buggy DJ: Update on local anesthetics: focus on levobupivacaine. Ther Clin Risk Manag. 2008 Apr;4(2):381-92. Pubmed
• "http://www.orgyn.com/resources/genrx/D003445.asp":http://www.orgyn.com/resources/genrx/D003445.asp
• Tullar, B., et al.: J. Med. Chem., 14, 891 (1971)
• Schmidt, A., et al.: Pharm. Res., 22, 2121 (1971)