104-31-4

Basic information

• Product Name: Benzonatate
• Synonyms: 4-(Butylamino)benzoicacid3,6,9,12,15,18,21,24,27-nonaoxao-ctacos-1-ylester;benzoicacid,4-(butylamino)-,3,6,9,12,15,18,21,24,27-nonaoxaoctacos-1-yles;benzononantin;benzononatine;exangit;km65;p-(butylamino)-benzoicaci2-(2-(2-(2-(2-(2-(2-(2-(2-methoxyethoxy)ethoxy)e;p-(n)-butylaminobenzoesaeure-(nonaaethylenglykol-monomethylaether)-ester
• CAS NO: 104-31-4
• Molecular Formula: C30H53NO11
• Molecular Weight: 603.74
• EINECS: 203-194-7
• Product Categories: Chemical Amines;Amines;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 104-31-4.mol

Chemical Properties

• Boiling Point: 649 °C at 760 mmHg
• Flash Point: 346.3 °C
• Appearance: /
• Density: 1.096 g/cm³
• Vapor Pressure: 9.98E-17mmHg at 25°C
• Refractive Index: 1.495
• Storage Temp.: Refrigerator, under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 2.20±0.39(Predicted)
• CAS DataBase Reference: Benzonatate(CAS DataBase Reference)
• NIST Chemistry Reference: Benzonatate(104-31-4)
• EPA Substance Registry System: Benzonatate(104-31-4)

Safety Data

• Hazardous Substances Data: 104-31-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Benzonatate is used as an antitussive agent for the treatment of coughs. It blocks Nav1.7 currents in a concentrationand voltage-dependent manner, inhibiting action potential firing in catecholamine A differentiated (CAD) cells. Additionally, it blocks 80% of Nav1.3 currents in N1E-115 cells when used at a concentration of 100 μM. In vivo, benzonatate reduces the frequency of the cough reflex without affecting its amplitude in anesthetized dogs.
Brand Name:
Tessalon (Forest)

Originator

Tessalon,Endo (Du Pont),US,1958

Manufacturing Process

4.42 parts of para-butylamino-benzoic acid ethyl ester are put with 16.0 parts of a mixture of polyethylene glycol monomethyl ethers, boiling at 180°-220°C at a pressure of 0.01 mm of mercury, in a closed reaction vessel which is fitted with an adjustable inlet tube for solvents and a connection for distilling off in vacuo. In order to dry the mixture completely, it is heated for an hour at 100°-105°C and absolute xylene is introduced under the surface of the mixture in vacuo at a pressure of 12 mm of mercury. There is thus a constant stream of xylene steam passing through the whole apparatus, which removes the last traces of moisture and any other volatile impurities. The xylene is condensed in a cooler. The whole is cooled to 20°-30°C and 0.06 part of sodium methylate dissolved in 0.6 part of methanol is added.Thereupon xylene is introduced again in vacuo at a temperature of 100°- 105°C whereby all the methanol and the ethanol formed during reesterification evaporates. The re-esterification is continued under these conditions until a specimen of the reaction mass is clearly soluble in cold water, which occurs after about 2-3 hours. There is now obtained in almost quantitative yield the ester of the formula wherein n stands for approximately 7 to 9, which still contains an excess of polyethylene glycol monomethyl ether. The ester is purified by dissolving in benzene and being washed several times with a sodium carbonate solution of 5% strength. It is advantageous to agitate all the washing solutions with fresh benzene. In this distribution between benzene and sodium carbonate solution the new ester remains in the benzene, the excess polyethylene glycol monomethyl ether and a small amount of brown impurities are taken up by the dilute soda solution. By evaporating the dried and filtered benzene solution there is obtained the new ester in the form of a colorless to very faintly yellow oil which is easily soluble in most organic solvents with the exception of aliphatic hydrocarbons. The new ester is precipitated from aqueous solutions when heated to about 42°C. but it dissolves again readily on cooling.

Therapeutic Function

Antitussive

Biological Functions

Benzonatate (TessaIon) is related to the local anesthetic tetracaine. It anesthetizes the stretch receptors in the lungs, thereby reducing coughing.Adverse reactions include hypersensitivity, sedation, dizziness, and nausea.

Mechanism of action

It is believed that it acts by two mechanisms: selective anesthesia of irritated receptors in the lungs and simultaneous suppression of the cough center.

Synthesis

Benzonatate, p-butylaminobenzoate 2,5,8,11,14,17,20,23,26-nonaoctacozan- 28-ol (23.2.2), is synthesized by reesterifying the ethyl ester of 4-butylaminobenzoic acid with the monomethyl ether nonaethylenglycol. It is a structural analog of the local anesthetic tetracaine.

InChI:InChI=1/C30H53NO11/c1-3-4-9-31-29-7-5-28(6-8-29)30(32)42-27-26-41-25-24-40-23-22-39-21-20-38-19-18-37-17-16-36-15-14-35-13-12-34-11-10-33-2/h5-8,31H,3-4,9-27H2,1-2H3

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Degradation kinetics of Benzonatate (cas 104-31-4) in aqueous solutions08/14/2019

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Benzonatate (cas 104-31-4) inhibition of voltage-gated sodium currents08/13/2019

Benzonatate was FDA-approved in 1958 as an antitussive. Its mechanism of action is thought to be anesthesia of vagal sensory nerve fibers that mediate cough. Vagal sensory neurons highly express the Nav1.7 subtype of voltage-gated sodium channels, and inhibition of this channel inhibits the coug...detailed

Genotoxicity assessment of the novel antitussive agent Benzonatate (cas 104-31-4) and its major metabolite08/12/2019

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