2-[(5-nitro-1,3-thiazol-2-yl)carbamoyl]phenyl acetate

• ChemBase ID: 389
• Molecular Formular: C12H9N3O5S
• Molecular Mass: 307.28196
• Monoisotopic Mass: 307.0262914
• SMILES: s1c(NC(=O)c2c(OC(=O)C)cccc2)ncc1[N+](=O)[O-]
• Canonical SMILES: CC(=O)Oc1ccccc1C(=O)Nc1ncc(s1)[N+](=O)[O-]
• InChI: InChI=1S/C12H9N3O5S/c1-7(16)20-9-5-3-2-4-8(9)11(17)14-12-13-6-10(21-12)15(18)19/h2-6H,1H3,(H,13,14,17)
• InChIKey: YQNQNVDNTFHQSW-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-[(5-nitro-1,3-thiazol-2-yl)carbamoyl]phenyl acetate
• IUPAC Traditional name: nitazoxanide
• Brand Name: Alinia; Fental; Phavic-1
• Synonyms: Nitazoxanida [INN-Spanish]; Nitazoxanid; Nitazoxanidum [INN-Latin]; Tizoxanide Glucuronide; NTZ; 2-Acetyloxy-N-[(5-nitro-2-thiazolyl)]benzamide; 2-(Acetolyloxy)-N-(5-nitro-2-thiazolyl)benzamide; nitazoxanide; Nitazoxanide; Nitazoxamide; 2-(Acetyloxy)-N-(5-nitro-2-thiazolyl)benzamide; Alinia; BRN 1225475; Cryptaz; DRG 0242; N-(5-Nitro-2-thiazolyl)salicylamide Acetate Ester; Nitacure; Nitarid; Nitazoxanida; Nixide; Nixoran; Nizonide; PH 5776; NTZ; 2-(Acetyloxy)-N-(5-nitro-2-thiazolyl)benzamide; Nitazoxanide

Database IDs

• CAS Number: 55981-09-4
• EC Number: 259-931-8
• MDL Number: MFCD00416599
• PubChem SID: 46507813; 160963852
• PubChem CID: 41684

CALCULATED PROPERTIES

JChem

• Acid pKa: 8.199224
• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): 2.1205907
• LogD (pH = 7.4): 2.0608385
• Log P: 2.1214147
• Molar Refractivity: 72.886 cm^3
• Polarizability: 27.28551 Å^3
• Polar Surface Area: 111.43 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.14
• LOG S: -4.61
• Solubility (Water): 7.55e-03 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; Methanol
• Apperance: Off White to Pale Yellow Solid
• Melting Point: 198-200°C
• Hydrophobicity(logP): 1.2

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• Storage Warning: IRRITANT
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 22-36/37/38
• Safety Statements: 26-36
• TSCA Listed: false
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302-H315-H319-H335
• GHS Precautionary statements: P261-P305 + P351 + P338
• Storage Temperature: 2-8°C

Product Information

• Purity: ≥98% (HPLC); 95+%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C12H9N3O5S

DETAILS

DrugBank - DB00507

• Drug Groups: approved; investigational
• Description: Nitazoxanide, also known by the brand name Alinia, is a synthetic nitrothiazolyl-salicylamide derivative and an anti-protozoal agent. It is approved for treatment of infectious diarrhea caused by Cryptosporidium parvum and Giardia lamblia in patients 1 year of age and older. Following oral administration it is rapidly hydrolyzed to its active metabolite, tizoxanide, which is 99% protein bound. Peak concentrations are observed 1–4 hours after administration. It is excreted in the urine, bile and feces. Untoward effects include abdominal pain, vomiting and diarrhea. [Wikipedia]
• Indication: For the treatment of diarrhea in adults and children caused by the protozoa Giardia lamblia and for the treatment of diarrhea in children caused by the protozoa Cryptosporidium parvum.
• Pharmacology: Nitazoxanide is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that nitazoxanide inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Nitazoxanide is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, nitazoxanide is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
• Toxicity: In acute studies in rodents and dogs, the oral LD₅₀ was higher than 10,000 mg/kg. Single oral doses of up to 4000 mg nitazoxanide have been administered to healthy adult volunteers without significant adverse effects.
• Affected Organisms: Protozoa
• Biotransformation: Rapidly hydrolyzed to an active metabolite, tizoxanide (desacetyl-nitazoxanide), followed by conjugation, primarily by glucuronidation to tizoxanide glucuronide.
• Absorption: The relative bioavailability of the suspension compared to the tablet was 70%. When administered with food the AUC and C_max increased by two-fold and 50%, respectively, for the tablet and 45 to 50% and ≤ 10%, respectively, for the oral suspension.
• Half Life: 3.5 hours in patients with normal renal function
• Protein Binding: Very High (greater than 99%), bound to proteins. Binding is not affected by degree of renal impairment.
• Elimination: Tizoxanide is excreted in the urine, bile and feces, and tizoxanide glucuronide is excreted in urine and bile. Approximately two-thirds of the oral dose of nitazoxanide is excreted in the feces and one-third in the urine.
• References: Parasitic infections. Am J Transplant. 2004 Nov;4 Suppl 10:142-55. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1627

Research Area: Infection
Biological Activity:
Nitazoxanide(Alinia, Annita) is a synthetic nitrothiazolyl-salicylamide derivative and an antiprotozoal agent. (IC50 for canine influenza virus ranges from 0.17 to 0.21 μM) The anti- protozoal activity of nitazoxanide is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction which is essential to anaerobic energy metabolism. [1] It has also been shown to have activity against influenza A virus. Nitazoxanide and tizoxanide inhibited virus replication of all canine influenza virus with 50% and 90% inhibitory concentrations ranging from 0.17 to 0.21 μM and from 0.60 to 0.76 μM, respectively. [2]

Sigma Aldrich - N0290

Biochem/physiol Actions
Nitazoxanide is an inhibitor of pyruvate-ferredoxin oxidoreductase (PFOR); Antimicrobial recently found to kill both non-replicating and replicating mycobacteria. FDA approved anti-parasitic drug (2002). Recent work (C & EN Sept. 14, 2009, p. 28) highlights that NTZ kills non-replicating and replicating TB bacteria and no apparent resistance is detected.

Toronto Research Chemicals - N490100

An anthelmintic (cestodes), antiprotozoal (cryptosporidium). Kills Mycobacterium tuberculosis.

REFERENCES

• Parasitic infections. Am J Transplant. 2004 Nov;4 Suppl 10:142-55. Pubmed
• Cavier, R., et al.: Eur. J. Med. Chem.-Chim. Ther., 13, 539 (1978)
• Dubreuil, L., et al.: Antimicrob. Ag. Chemother., 40, 2266 (1978)
• Stockis, A., et al.: Int. J. Clin. Pharmacol. Ther., 34, 349 (1978)
• Nathan, C., et al.: J. Med. Chem. 52, 5789 (1978)