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Ethambutol

Product Name
Ethambutol
CAS No.
74-55-5
Chemical Name
Ethambutol
Synonyms
emb;C06984;tibutol;MGC71745;diambutol;Etambutol;ETHAMBUTOL;d-ethambutol;Ethambutolum;Aethambutolum
CBNumber
CB3324345
Molecular Formula
C10H24N2O2
Formula Weight
204.31
MOL File
74-55-5.mol
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Ethambutol Property

Melting point:
199-204℃
alpha 
D25 +13.7° (c = 2 in water)
Boiling point:
345℃
Density 
1.0048 (rough estimate)
refractive index 
1.4610 (estimate)
RTECS 
EL3640000
Flash point:
>110°(230°F)
storage temp. 
Keep in dark place,Sealed in dry,2-8°C
solubility 
Soluble in DMSO
form 
Powder
pka
pKa 6.6 (H2O) (Uncertain);9.5(H3O) (Uncertain)
Water Solubility 
Soluble in water. Also soluble in chloroform and methylene chloride
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Safety

Hazardous Substances Data
74-55-5(Hazardous Substances Data)
Toxicity
LD50 oral in rat: 998mg/kg
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H302Harmful if swallowed

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P330Rinse mouth.

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N-Bromosuccinimide Price

TRC
Product number
E889808
Product name
Ethambutol
Packaging
50g
Price
$330
Updated
2021/12/16
Usbiological
Product number
136067
Product name
EMB
Packaging
50ug
Price
$664
Updated
2021/12/16
ApexBio Technology
Product number
B3418
Product name
Ethambutol
Packaging
1g
Price
$49
Updated
2021/12/16
ApexBio Technology
Product number
B3418
Product name
Ethambutol
Packaging
5g
Price
$90
Updated
2021/12/16
Biorbyt Ltd
Product number
orb599980
Product name
EMB
Packaging
10μg
Price
$290.7
Updated
2021/12/16
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Ethambutol Chemical Properties,Usage,Production

Originator

Myambutol,Lederle,US,1967

Uses

Ethambutol is an antitubercular antibiotic.

Uses

Antibacterial.

Definition

ChEBI: An ethylenediamine derivative that is ethane-1,2-diamine in which one hydrogen attached to each of the nitrogens is sutstituted by a 1-hydroxybutan-2-yl group (S,S-configuration). It is a bacteriostatic antimycobacterial d ug, effective against Mycobacterium tuberculosis and some other mycobacteria. It is used (as the dihydrochloride salt) in combination with other antituberculous drugs in the treatment of pulmonary and extrapulmonary tuberculosis; resistant str ins of M. tuberculosis are readily produced if ethambutol is used alone.

Indications

Ethambutol is a water-soluble, heat-stable compound that acts by inhibition of arabinosyl transferase enzymes that are involved in cell wall biosynthesis. Nearly all strains of M. tuberculosis and M. kansasii and most strains of Mycobacterium avium-intracellulare are sensitive to ethambutol. Drug resistance relates to point mutations in the gene (EmbB) that encodes the arabinosyl transferases that are involved in mycobacterial cell wall synthesis.

Manufacturing Process

To 27 grams (2.55 mols) of 2-amino-1-butanol was added 100 grams (1.0 mol) of ethylene dichloride. The mixture was heated at reflux and in a few minutes, the exothermic reaction required the removal of exterior heating. After 10 minutes, exterior heating was recommenced for an additional 20 minutes. The hot mixture was then treated with 300 ml of methanol and then cautiously with 84 grams (2.1 mols) of sodium hydroxide in 80 ml of water.
The precipitated sodium chloride was removed by filtration. The excess 2- amino-1-butanol distilled as light yellow oil at 83° to 87°C/13 mm. The viscous residue distilled at 165° to 170°C/0.6 mm as a light yellow oil which tended to solidify in the air condenser; yield, 108 grams.
Recrystallization by dissolving in 80 ml of hot ethanol, adding about 150 ml of petroleum ether (BP 90° to 100°C) and cooling at 5°C overnight, gave 64 grams of white crystals melting at 128° to 132.5°C. This, on recrystallization from 100 ml of 95% ethanol, gave 35 grams of white crystals melting at 134.5° to 136°C and a second crop of 10 grams melting at 132.5° to 134°C which is the meso base. Its dihydrochloride melts at 202° to 203°C.
From the ethanolic filtrates upon addition of 130 ml of about 4 N ethanolic hydrochloric acid and cooling, there was obtained 55 grams of white crystals melting at 176.5° to 178°C and a second crop of 10 grams melting at 171.5° to 174.5°C. This is the dl racemate dihydrochloride.

brand name

Myambutol (Stat Trade);Aethambutolum;Embutol;Etbutol.

Therapeutic Function

Antitubercular

Antimicrobial activity

Ethambutol is active against several species of mycobacteria and nocardiae. MICs on solid media are: M. tuberculosis 0.5–2 mg/L; M. kansasii 1–4 mg/L; other slowly growing mycobacteria 2–8 mg/L; rapidly growing pathogens 2–16 mg/L; Nocardia spp. 8–32 mg/L.
Resistance is uncommon and is a multistep process due to mutations in the embA, embB and embC gene cluster. A mutation in codon 306 of the embB gene predisposes to the development of resistance to a range of antituberculosis agents, possibly by affecting cell-wall permeability.

Pharmaceutical Applications

A synthetic ethylenediamine derivative formulated as the dihydrochloride for oral administration. The dry powder is very soluble and stable.

Mechanism of action

The mechanism of action of EMB remains unknown, although mounting evidence suggests a specific site of action for EMB. It has been known for some time that EMB affects mycobacterial cell wall synthesis; however, the complicated nature of the mycobacterial cell wall has made pinpointing the site of action difficult. In addition to the peptidoglycan portion of the cell wall, the mycobacterium have a unique outer envelop consisting of arabinofuranose and galactose (AG), which is covalently attached to the peptidoglycan and an intercalated framework of lipoarabinomannan (LAM) . The AG portion of the cell wall is highly branched and contains distinct segments of galactan and distinct segments of arabinan. At various locations within the arabinan segments (terminal and penultimate), the mycolic acids are attached to the C-5′ position of arabinan. Initially, Takayama et al. reported that EMB inhibited the synthesis of the AG portion of the cell wall. More recently, it has been reported that EMB inhibits the enzymes arabinosyl transferase. One action of arabinosyl transferase is to catalyze the polymerization of D-arabinofuranose, leading to AG. Ethambutol mimics arabinan, resulting in a buildup of the arabinan precursor β-D-arabinofuranosyl- 1-monophosphoryldecaprenol and, as a result, a block of the synthesis of both AG and LAM. The mechanism of resistance to EMB involves a gene overexpression o

Pharmacology

Orally administered ethambutol is well absorbed (70–80%) from the gut, and peak serum concentrations are obtained within 2 to 4 hours of drug administration; it has a half-life of 3 to 4 hours. Ethambutol is widely distributed in all body fluids, including the cerebrospinal fluid, even in the absence of inflammation.A majority of the unchanged drug is excreted in the urine within 24 hours of ingestion. Up to 15% is excreted in the urine as an aldehyde and a dicarboxylic acid metabolite. Ethambutol doses may have to be modified in patients with renal failure.

Pharmacokinetics

Oral absorption: c. 80%, but some patients absorb it poorly
Cmax 25 mg/kg oral: 2–6 mg/L after 2–3 h
Plasma half-life: 10–15 h
Volume of distribution: >3 L/kg
Plasma protein binding: 20–30%
Absorption is impeded by aluminum hydroxide and alcohol. It is concentrated in the phagolysosomes of alveolar macrophages. It does not enter the cerebrospinal fluid (CSF) in health but CSF levels of 25–40% of the plasma concentration, with considerable variation between patients, are achieved in cases of tuberculous meningitis.
Various metabolites are produced, including dialdehyde, dicarboxylic acid and glucuronide derivatives. Around 50% is excreted unchanged in the urine, with an additional 10–15% as metabolites, and 20% is excreted unchanged in feces.

Clinical Use

Tuberculosis (initial intensive phase of short-course therapy)
Other mycobacterioses (M. kansasii, M. xenopi, M. malmoense and the M. avium complex) (with appropriate additional drugs)

Clinical Use

Ethambutol has replaced aminosalicylic acid as a first-line antitubercular drug. It is commonly included as a fourth drug, along with isoniazid, pyrazinamide, and rifampin, in patients infected with MDR strains. It also is used in combination in the treatment of M. aviumintracellulare infection in AIDS patients.

Side effects

The major toxicity associated with ethambutol use is retrobulbar neuritis impairing visual acuity and redgreen color discrimination; this side effect is dose related and reverses slowly once the drug is discontinued. Mild GI intolerance, allergic reaction, fever, dizziness, and mental confusion are also possible. Hyperuricemia is associated with ethambutol use due to a decreased renal excretion of urates; gouty arthritis may result.

Side effects

The most important side effect is optic neuritis, which may be irreversible if treatment is not discontinued. This complication is rare if the higher dose (25 mg/kg) is given for no more than 2 months. National codes of practice for prevention of ocular toxicity should be adhered to; in particular, patients should be advised to stop therapy and seek medical advice if they notice any change in visual acuity, peripheral vision or color perception, and the drug should not be given to young children and others unable to comply with this advice.
Other side effects include gastrointestinal upsets, peripheral neuritis, arthralgia, nephritis, myocarditis, hyperuricemia, dermal hypersensitivity and, rarely, thrombocytopenia and hepatotoxicity.

Synthesis

Ethambutol, (±)-N,N-ethylenbis-(2-aminobutan-1-ol) (34.1.4), is synthesized in several different ways. According to one of them, nitropropane undergoes oxymethylation using formaldehyde, and the nitro group in the resulting 2-nitrobutanol (34.1.2) is reduced by hydrogen to an amino group, making racemic (±) 2-aminobutanol. L (£?) tartaric acid is used to separate (£?) 2-aminobutanol (34.1.3). Reacting this with 1, 2-dichloroethane in the presence of sodium hydroxide gives ethambutol (34.1.4).

An alternative method of synthesis consists of preparing (£?) 2-aminobutanol (34.1.3) by reducing ethyl ester of L-2-aminobutyric acid hydrochloride with hydrogen using simultaneously Raney nickel and platinum oxide catalysts. This gives pure (£?) 2-aminobutanol. Reacting this with 1,2-dichloroethane in the presence of sodium hydroxide gives the desired ethambutol (34.1.4).

The third way of synthesis is very interesting and resembles of the Ritter reaction, but which takes place in the presence of chlorine. This method consists of reacting 1-butene and acetonitrile in the presence of chlorine, which evidently results in the 1,4-addition of chlorine to the product of the Ritter reaction, forming an intermediate dichloride (33.1.5), which is hydrolyzed with water to make N-[1-(chloromethyl)-propyl]-acetamide (33.1.6). Heating this product with hydrochloric acid gives racemic (±) 2-aminobutanol, from which (£?) 2-aminobutanol (34.1.3) is isolated as described above using L (£?) tartaric acid. Reacting this with 1,2-dichloroethane in the presence of sodium hydroxide gives the desired ethambutol (34.1.4)

Ethambutol Preparation Products And Raw materials

Raw materials

Preparation Products

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Ethambutol Suppliers

LGM Pharma
Tel
1-(800)-881-8210
Fax
615-250-9817
Email
inquiries@lgmpharma.com
Country
United States
ProdList
2127
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Syntechem Co.,Ltd
Tel
Fax
E-Mail Inquiry
Email
info@syntechem.com
Country
China
ProdList
12990
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57
Spectrum Chemical Manufacturing Corp.
Tel
021-021-021-67601398-809-809-809 15221380277
Fax
021-57711696
Email
marketing_china@spectrumchemical.com
Country
China
ProdList
9664
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Shanghai Macklin Biochemical Co.,Ltd.
Tel
15221275939 15221275939
Fax
021-50706099
Email
shenlinxing@macklin.cn
Country
China
ProdList
15873
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Hubei Jusheng Technology Co.,Ltd
Tel
027-59599241 18871490274
Fax
027-59599241
Email
1400878000@qq.com
Country
China
ProdList
9972
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58
LETOPHARM LIMITED
Tel
+86-21-5821 5861
Fax
+86-21-5106 2861
Email
sales@letopharm.com
Country
China
ProdList
2384
Advantage
58
Chizhou Kailong Import and Export Trade Co., Ltd.
Tel
Fax
-
Email
xg01_gj@163.com
Country
China
ProdList
9503
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50
ShangHai Biochempartner Co.,Ltd
Tel
17754423994 17754423994
Fax
QQ:2853530913
Email
2853530910@QQ.com
Country
China
ProdList
8018
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62
Beijing Jin Ming Biotechnology Co., Ltd.
Tel
010-60605840 18892239720
Fax
010-60605840
Email
psaitong@jm-bio.com
Country
China
ProdList
12308
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58
Anhui kuer Bioengineering Co., Ltd
Tel
0551-65171243 13810511747
Email
kuer@kuerhuaxue.com
Country
China
ProdList
2996
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View Lastest Price from Ethambutol manufacturers

Guangzhou PI PI BIOTECH INC
Product
Ethambutol 74-55-5
Price
US $0.00-0.00/mg
Min. Order
10mg
Purity
90%+
Supply Ability
10g
Release date
2021-09-16
Hebei Zhanyao Biotechnology Co. Ltd
Product
Ethambutol 74-55-5
Price
US $10.00/Kg/Bag
Min. Order
1Kg/Bag
Purity
99%
Supply Ability
20 Tons
Release date
2021-11-18
Dideu Industries Group Limited
Product
Ethambutol 74-55-5
Price
US $1.10/g
Min. Order
1g
Purity
99.9%
Supply Ability
100 Tons Min
Release date
2021-07-16

74-55-5, EthambutolRelated Search:


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  • (+)-2,2’-(ethylenediimino)di-1-butanol
  • (+)-n,n’-bis(1-(hydroxymethyl)propyl)ethylenediamine
  • (+)-s,s-ethambutol
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