 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C14H16CL3NO2 |
| Molecular Weight | 336.64 |
| Exact Mass | 335.024 |
| CAS # | 156052-68-5 |
| PubChem CID | 122087 |
| Appearance |
White solid Fine, white powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 415.4±45.0 °C at 760 mmHg |
| Melting Point | 159.5-161ºC |
| Flash Point | 205.0±28.7 °C |
| Vapour Pressure | 0.0±1.0 mmHg at 25°C |
| Index of Refraction | 1.545 |
| LogP | 4.84 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 20 |
| Complexity | 365 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CCC(C(CCl)=O)(NC(C1=CC(Cl)=C(C(Cl)=C1)C)=O)C |
| InChi Key | SOUGWDPPRBKJEX-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C14H16Cl3NO2/c1-4-14(3,12(19)7-15)18-13(20)9-5-10(16)8(2)11(17)6-9/h5-6H,4,7H2,1-3H3,(H,18,20) |
| Chemical Name | 3,5-dichloro-N-(1-chloro-3-methyl-2-oxopentan-3-yl)-4-methylbenzamide |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Mean plasma radioactivity concentrations peaked at 8 hr following 10 mg/kg or 1000 mg/kg zoxamide, and time of one-half peak concentration was 22 hr. Tissue levels as percentage of administered dose were generally about twice as high in the 10 mg/kg groups compared to high dose rats, consistent with the above evidences of poor absorption at 1000 mg/kg. Only the alimentary tract and liver had remarkably high concentrations at 8 hr, with marked reduction in most tissues by 22 hr after dosing. Thus zoxamide and its metabolites tend not accumulate in the body. There were no remarkable sex differences in zoxamide disposition. Investigators studied all major elements of a metabolism study in male and female Crl:CD BR rats, including excretion patterns following a single gavage dose (in corn oil) of 10 mg/kg or a single dose of 1000 mg/kg labeled zoxamide, or single dose of 10 mg/kg labeled zoxamide after 2 weeks of administration of 200 ppm non-labeled zoxamide in diet. Tissue distribution of residues was determined after 8, 22, and 120 hr ... and blood kinetics were assessed. Exhaled air was evaluated for (14)C content (this was found not to be a significant route). ... Administration of 10 mg/kg zoxamide led to appreciable recovery of unaltered zoxamide in feces (12-23%). Much higher unaltered zoxamide were found in feces (72-74%) following a 1000 mg/kg dose. At least 71% of administered dose was found in feces after 10 mg/kg treatment (with or without dietary pre-treatment). Zoxamide was rapidly and extensively absorbed, metabolized and excreted. Approximately 61% of the administered dose was systemically absorbed. Absorption was less complete in high dose groups. Plasma concentrations peaked approximately 8 hr post dose. Residue concentrations were highest in organs associated with absorption (liver, stomach, intestines). ... Elimination from plasma was bi-phasic with an elimination half-life of 12-14 hr. No residues were detected in expired air. Altogether, in urine and feces, 32 separate metabolites were identified; no single metabolite other than the parent accounted for more than 10% of the administered dose. Over 85% of the administered dose in single dose studies was excreted within 24-48 hr; the predominant route of excretion was hepatobiliary. No evidence of accumulation of the parent compound or its metabolites was observed. There were no apparent sex related differences. The two major potato metabolites (RH-141452 and RH-141455), which were minor rat metabolites, were studied in separate metabolism studies. More than 97% of the administered dose (RH-141452) was excreted within 24 hr. Greater than 94% was eliminated unchanged in urine. Two glucuronide conjugates and a glycine conjugate (about 3% of the administered dose) were found in urine. An additional 1.6% of the administered dose was excreted unchanged in the feces. Excretion of RH-141455 was slower: 47% of the administered dose was excreted within 24 hr, with an additional 32% of the administered dose excreted between 24 and 48 hr. Greater than 92% of the administered dose was recovered (about 73% in feces, 11% in urine and 9% in cage rinse) as unchanged RH-141455 (>96%). /Metabolites/ Metabolism / Metabolites Investigators studied all major elements of a metabolism study in male and female Crl:CD BR rats ... Bile ducts were cannulated to assess degree of biliary excretion and associated metabolites. Investigators isolated 36 compounds including parent zoxamide in urine and/or feces. Bile contained 17 separable components. Major metabolites by each route were identified. ... Several metabolic routes were evident from analysis of fecal metabolites, including as initial steps: reductive dehalogenation, hydrolysis to provide an alpha-keto alcohol, or glutathione conjugation at the chloro group of the side chain. Often the final metabolites were products of subsequent oxidation to provide benzoic acid substituents or oxidation of the side chain to one of several carboxylic acid moieties, depending upon the amount of degradation of the side chain. There was no single dominant urinary metabolite. Most of these had been oxidized to expose several polar groups, and included several glutathione and glucuronide conjugation products. Rats treated with 10 mg/kg [(14)C]-/zoxamide/ following 2 weeks of administration of 200 ppm non-labeled zoxamide had excretion patterns similar to those of non-pre-treated rats. Biliary metabolites in cannulated rats constituted 46-48% of dose. Various glutathione derivatives predominated in the bile, and some residues underwent hydrolysis or reductive dehalogenation followed by glucuronide formation. Four male Crl:CD BR rats were dosed by gavage in water once at 1000 mg/kg with 3,5-dichloro-4-hydroxymethyl benzoic acid, (RH-141,452), a metabolic product of zoxamide. Purity of unlabeled test article was 100%. Radiopurity of (14)C-ring-labeled test article was 98%. Investigators assessed recoveries in urine, feces, and exhaled air, and identified major metabolites in urine and feces. Urinary excretion was about 98% of dose, feces 1.7%, and expired air about 0.01%. Nearly all of urinary excretion was complete within 24 hr, and most fecal excretion occurred within 48 hr. About 94% of dose was excreted in urine as the test article. Collectively, three minor metabolites accounted for another 3% of urinary label (glucuronides of the hydroxyl or carboxylic acid groups, or glycine conjugate of the carboxylic acid group). Nearly all fecal label represented test article Four male Crl:CD BR rats were dosed by gavage in water once at 1000 mg/kg with ring-labeled [(14)C]- RH-141,455 (this is the dicarboxylic acid metabolite of zoxamide). Purity of unlabeled RH-141,455 was 98.77%. Radiopurity of (14)C- RH-141,455 was > 96%. Investigators assayed residues in urine, feces, and exhaled air, and identified major metabolites in urine and feces. Tissues were not analyzed at 168 hr termination of rats, since nearly all label could be found in excreta. Recoveries of radiolabel averaged 75.5% in feces, 11.0% in urine, and 9.3% in cage rinse. Due to diarrhea, much of the cage rinse may have represented fecal output. About 0.01% of dose was found in expired air. Label recovery in feces, urine, or cage rinse dropped off quickly after the first 48 hr after dosing. Parent compound was the only significant peak detected after HPLC separation of extracts of fecal and urinary samples. ... Metabolism occurred by primary hydrolysis, glutathione mediated reactions and reductive dehalogenation; secondary oxidation of the aromatic methyl and the aliphatic side chain; and terminal glucuronic acid and amino acid conjugations. Induction of metabolism (glutathione transferase and/or glutathione cofactor) appeared to occur. ... Altogether, in urine and feces, 32 separate metabolites were identified; no single metabolite other than the parent accounted for more than 10% of the administered dose. ... There were no apparent sex related differences. The in vitro mammalian metabolism of the fungicide zoxamide is related to its in vitro mammalian toxicity. After incubation of zoxamide with rat liver microsomes leading to practically 100% metabolism (mostly hydroxylated zoxamide), the cytotoxicity (methyl thiazole tetrazolium (MTT) test) and the mitosis-inhibiting potential (shown by cell count and by cell cycle analysis) for V79 were not distinguishable from those of zoxamide, demonstrating that the hydroxylation of zoxamide did not change the cytotoxicity or mitosis-inhibiting potential as determined by these assays. After incubation of zoxamide with rat liver S9 predominantly leading to conjugation with glutathione, and after incubation of zoxamide with rat liver slices predominantly leading to the glucuronide of the hydroxylated zoxamide, these activities were eliminated demonstrating that the glutathione conjugate and the glucuronide had lost the activities in these assays due either to no intrinsic potential of these conjugates or to their inability to penetrate the plasma membrane of mammalian cells. It is concluded that the metabolic hydroxylation of zoxamide did not change its activity in the assays used for investigating its influence on cell proliferation, cell cycle and cytotoxicity, while the formation of conjugates with glutathione or glucuronic acid led to the apparent loss of these activities. ... Biological Half-Life Zoxamide was rapidly and extensively absorbed, metabolized and excreted. ... Elimination from plasma was bi-phasic with an elimination half-life of 12-14 hr. |
| Toxicity/Toxicokinetics |
Toxicity Summary IDENTIFICATION AND USE: Zoxamide is a fine, white powder. It is used as a fungicide. HUMAN EXPOSURE AND TOXICITY: Zoxamide is harmful if absorbed through the skin and causes moderate eye irritation. Prolonged or frequent repeated skin contact may cause allergic reactions in some individuals. It is a dermal sensitizer. ANIMAL STUDIES: Zoxamide was considered to be of low acute toxicity by the oral, dermal and inhalation routes in rats. It was moderately irritating when applied to the skin of rabbits, and was minimally irritating when instilled into the eyes of the same species. Results of skin sensitization testing in guinea pigs were positive. Acute and short-term (90-day) neurotoxicity studies conducted in the rat did not demonstrate any neurotoxic potential for zoxamide. It was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA102. ECOTOXICITY STUDIES: The NOEC of zoxamide for the early life-stages of the rainbow trout (Oncorhynchus mykiss) and the sheepshead minnow (Cyprinodon variegatus) were 3.48 ug a.i./L and 40 ug a.i./L, respectively, and for a full life cycle in the fathead minnow (Pimephales promelas) 60 ug a.i./L. Toxicity Data LC50 (rat) > 5,300 mg/m3 Non-Human Toxicity Values LD50 Rat dermal 2000 mg/kg LD50 Rat oral 5000 mg/kg LD50 Mouse oral 5000 mg/kg |
| References |
[1]. Mei X, et al. Proteomic analysis on zoxamide-induced sensitivity changes in Phytophthora cactorum. Pestic Biochem Physiol. 2015 Sep;123:9-18. [2]. David H. Young, et al. Mode of Action of Zoxamide (RH-7281), a New Oomycete Fungicide. Pesticide Biochemistry and Physiology. Volume 69, Issue 2, February 2001, Pages 100-111. |
| Additional Infomation |
3,5-dichloro-N-(1-chloro-3-methyl-2-oxopentan-3-yl)-4-methylbenzamide is a member of the class of benzamides obtained by formal condensation of the carboxy group of 3,5-dichloro-4-methylbenzamide with the amino group of 3-amino-1-chloro-3-methylpentan-2-one. It is a member of benzamides, an alpha-chloroketone and a dichlorobenzene. Zoxamine is a fungicide used for the control of various fungal inflections including blight in potatoes and tomatoes. It has a rainfast preventative action with residual properties and acts by inhibiting nuclear division. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9705 mL | 14.8527 mL | 29.7053 mL | |
| 5 mM | 0.5941 mL | 2.9705 mL | 5.9411 mL | |
| 10 mM | 0.2971 mL | 1.4853 mL | 2.9705 mL |