CAS 452-35-7|Ethoxzolamide

Introduction:Basic information about CAS 452-35-7|Ethoxzolamide, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Common NameEthoxzolamide
CAS Number452-35-7Molecular Weight258.31700
Density1.47g/cm3Boiling Point464.9ºC at 760mmHg
Molecular FormulaC9H10N2O3S2Melting Point190-193ºC(lit.)
MSDSChineseUSAFlash Point235ºC
Symbol
GHS07
Signal WordWarning

Names

Nameethoxzolamide
SynonymMore Synonyms

Ethoxzolamide BiologicalActivity

DescriptionEthoxzolamide is a carbonic anhydrase inhibitor with Ki of 1 nM.
Related CatalogSignaling Pathways >>Metabolic Enzyme/Protease >>Carbonic AnhydraseResearch Areas >>Inflammation/ImmunologyResearch Areas >>Infection
Target

Ki: 1 nM (carbonic anhydrase)[1]

In VitroEthoxzolamide (ETZ) treatment causes >90% inhibition of reporter GFP fluorescence in infected macrophages. Moreover, in a 9-day macrophage survival assay, Ethoxzolamide (ETZ) treatment significantly inhibits the ability of M. tuberculosis to grow intracellularly[2].
In VivoIt is discovered that the lipid-soluble ethoxzolamide is converted in vivo to a water-soluble metabolite, while retaining high activity againstt the enzyme. At the minimal dose for maximal effect (4 mg/kg i.v. at 45 min) the IOP lowering is 4.2 mmHg, the concentration in anterior uvea is 2.5 pmol/kg, and the fractional inhibition of the enzyme (i) is 0.9995. The effect declines rapidly, attributable to the very short half-life of drug in plasma, leading to depletion of free drug in the anterior uvea and other tissues[1]. Ethoxzolamide (ETZ) strongly downregulates GFP reporter fluorescence in mouse lungs, with 3-fold inhibition of GFP signal compare to that in the mock-treating control. There is a significant reduction of bacterial survival in the lungs of ETZ-treating mice compare to the mock-treating control[2].
Cell AssayBMDMs are treated with 80 μM Ethoxzolamide (ETZ) or an equivalent volume of DMSO every 2 days for 9 days total. At days 3, 6, and 9, intracellular bacteria are quantified by lysing macrophage monolayers and performing serial dilution plating of lysates on 7H10 agar. For fluorescence microscopy experiments, macrophages are seeded on glass coverslips before infection with M. tuberculosis CDC1551. Samples are treated every 2 days with 100 μM Ethoxzolamide (ETZ) or an equal volume of DMSO for 9 days[2].
Animal AdminRats (male, 300–325 g) are randomly selected into 2 groups (n=6 each group) and Ethoxzolamide (EZ) is administered at a dose of 0.18 mg/kg (in PEG 300: ethanol, 1:1) via i.v. injection through the tail vein. Blood samples (about 50-100 µL) are collected in heparinizing tubes at 0, 15, 30, 60, 120, 180, 240, 360, 540, and 1440 min post-injection, via tail snip with isoflurane as anesthetic. Plasma samples are prepared and stored at -80 °C until analysis. To study the distribution in brain, rats in group 1 are scarified at 6 hours and rats in group 2 are scarified at 24 hours to collect the brain tissues. Those blood samples from group 2 are analyzed to generated PK profile[3].
References

[1]. Maren TH, et al. Relations among IOP reduction, ocular disposition and pharmacology of the carbonic anhydrase inhibitor ethoxzolamide. Exp Eye Res. 1992 Jul;55(1):73-9.

[2]. Benjamin K. Johnson, et al. The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits theMycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence. Antimicrob Agents Chemother. 2015 Aug; 59(8): 4436–4445.

[3]. Song Gao, et al. Development and validation of an UPLC-MS/MS method for the quantification of ethoxzolamide in plasma and bioequivalent buffers: Applications to absorption, brain distribution, and pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Apr 1; 0: 54–59.

Chemical & Physical Properties

Density1.47g/cm3
Boiling Point464.9ºC at 760mmHg
Melting Point190-193ºC(lit.)
Molecular FormulaC9H10N2O3S2
Molecular Weight258.31700
Flash Point235ºC
Exact Mass258.01300
PSA118.90000
LogP3.12350
Vapour Pressure8.05E-09mmHg at 25°C
Index of Refraction1.644
InChIKeyOUZWUKMCLIBBOG-UHFFFAOYSA-N
SMILESCCOc1ccc2nc(S(N)(=O)=O)sc2c1
Storage condition2-8℃

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :
DL6390000
CHEMICAL NAME :
2-Benzothiazolesulfonamide, 6-ethoxy-
CAS REGISTRY NUMBER :
452-35-7
BEILSTEIN REFERENCE NO. :
0212240
LAST UPDATED :
199612
DATA ITEMS CITED :
1
MOLECULAR FORMULA :
C9-H10-N2-O3-S2
MOLECULAR WEIGHT :
258.33
WISWESSER LINE NOTATION :
T56 BN DSJ CSZW GO2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
3300 mg/kg
SEX/DURATION :
female 1-22 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 1,51,1968

Safety Information

Symbol
GHS07
Signal WordWarning
Hazard StatementsH315-H319-H335
Precautionary StatementsP261-P305 + P351 + P338
Personal Protective Equipmentdust mask type N95 (US);Eyeshields;Gloves
Hazard CodesXi: Irritant;
Risk PhrasesR36/37/38
Safety Phrases26
RIDADRNONH for all modes of transport
WGK Germany3
RTECSDL6390000
HS Code2935009090

Customs

HS Code2935009090
Summary2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%

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Synonyms

Ethamide
6-ethoxy-1,3-benzothiazole-2-sulfonamide
Glaucotensil
Ethoxyzolamide
Ethoxazolamide
2-Benzothiazolesulfonamide,6-ethoxy
EINECS 207-199-5
MFCD00057089
Etoxzolamide
6-Ethoxy-2-benzothiazolesulfonamide
Cardrase
Diuretic C
6-ethoxybenzothiazole-2-sulphonamide
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