-Metalaxyl) Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C15H21NO4 |
| Molecular Weight | 279.33 |
| Exact Mass | 279.147 |
| CAS # | 70630-17-0 |
| Related CAS # | Metalaxyl-M-d6;1398112-32-7 |
| PubChem CID | 11150163 |
| Appearance |
Fine, white powder ... Colorless crystals ... . |
| Density | 1.117 g/cm3 |
| Boiling Point | 394.3ºC at 760 mmHg |
| Melting Point | 38.7ºC |
| Flash Point | 192.3ºC |
| Index of Refraction | 1.527 |
| LogP | 1.844 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 20 |
| Complexity | 335 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CC1=C(C(=CC=C1)C)N([C@H](C)C(=O)OC)C(=O)COC |
| InChi Key | ZQEIXNIJLIKNTD-GFCCVEGCSA-N |
| InChi Code | InChI=1S/C15H21NO4/c1-10-7-6-8-11(2)14(10)16(13(17)9-19-4)12(3)15(18)20-5/h6-8,12H,9H2,1-5H3/t12-/m1/s1 |
| Chemical Name | methyl (2R)-2-(N-(2-methoxyacetyl)-2,6-dimethylanilino)propanoate |
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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
| Targets | IC50: fungi[1] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion In a single dose study, male & female rats were administed 0.5 or 25 mg/kg of metalaxyl by gavage. Over 60% of the low or high dose was excreted within 24 hr in urine or feces. Negligible amounts were eliminated in expired air. Low tissue residues 6 days after treatment indicated no appreciable bioaccumulation. Female rats eliminated the majority of the dose (55-65%) in urine, & males eliminated most (60-70%) in feces. Although metabolites were not identified, the chromatographic pattern was similar for both sexes & doses. Metabolism / Metabolites A recent comprehensive study evaluated metalaxyl pharmacokinetics with male & female Sprague-Dawley rats following a single iv dose (1 mg/kg), single oral low dose (1 mg/kg), single oral high dose (200 mg/kg), or repeated oral low doses (1 mg/kg/day for 14 days). The absorption distribution, & elimination patterns were consistent with previous findings. No major dose or sex differences were observed except that urine was th predominant elimination route for females whereas feces was the major route for males. Metalaxyl was readily absorbed (similar iv & oral elimination profiles), extensively metabolized (<1% parent compound in excreta), & rapidly eliminated (70-80% in 24 hr). Ten metabolites were identified. The majority of urinary metabolites were conjugated (glucuronide or sulfate) whereas fecal metabolites were mostly unconjugated. The major metabolite in urine & feces was N-(2,6-dimethylphenyl)-N-(hydroxyacetyl) alanine. Three major & one minor metabolic pathways were proposed. One pathway involved hydrolysis of the ether, followed by oxidation of the resulting alcohol, ester hydrolysis, or N-dealkylation of the ester chain. A second pathway involved oxidation of an aromatic methyl to the benzylic acid or ester hydrolysis. The third major pathway was ester hydrolysis, sometimes followed by benzylic acid formation. The minor pathway involved hydroxylation at the meta position of the phenyl ring. Two major metabolited in urine were not identified. ... |
| Toxicity/Toxicokinetics |
Interactions Because metalaxyl is used on tobacco, a 90 day smoke inhalation study was conducted. Male & female Fischer 344 rats were exposed to smoke form cigarettes containing 0, 130, 3,900, or 13,000 ppm of metalaxyl for 4 hr/day, 5 days/wk. The max air concn of metalaxyl was 5 ug/L. The concns in test cigarettes were 100-1,000 times avg residue levels & 30-100 times greater than the expected max residue levels. Although the study was limited in its ability to simulate human exposure, the results were adequate to demonstrate toxicological effects from exposures are unlikely beyond that from exposures associated with heavy smoking. The profile of residues in inhalable smoke indicated 30% was metalaxyl, 4% was 2,6-dimethylaniline, & 65% was unidentified material. Non-Human Toxicity Values LD50 Rat oral 669 mg/kg LD50 Mouse oral 788 mg/kg LD50 Hamster oral 7120 mg/kg LD50 Rabbit dermal >6000 mg/kg |
| References | [1]. Yinjun Zhang, et al. Bio-preparation of (R)-DMPM using whole cells of Pseudochrobactrum asaccharolyticum WZZ003 and its application on kilogram-scale synthesis of fungicide (R)-metalaxyl. Biotechnol Prog |
| Additional Infomation |
Metalaxyl-M is a methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alaninate that is the more active R-enantiomer of metalaxyl. A systemic fungicide, it is active against phytopathogens of the order Peronosporales and is used to conrtrol Pythium in a number of vegetable crops. It has a role as an agrochemical. It is a methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alaninate, a D-alanine derivative, an acylamino acid fungicide and an anilide fungicide. It is functionally related to a D-alanine. It is an enantiomer of a (S)-metalaxyl. Mechanism of Action Intraperitoneal injection of metalaxyl (250 mg/kg) produced a decrease in heart rate lasting for more than 60 min in anesthetized rats. Pretreatment of rats with phentolamine (a nonselective alpha-adrenoreceptor antagonist, ip at 20 mg/kg) and prazosin (an alpha 1-adrenoreceptor antagonist, ip at 5 mg/kg) significantly reduced the bradycardia induced by metalaxyl. Yohimbine (an alpha 2-adrenoreceptor antagonist, ip at 10 mg/kg) did not change the effect of metalaxyl on heart rate. The results suggest that alpha 2-adrenoreceptors mediate the bradycardic effect of metalaxyl. The ability of metalaxyl ... to affect specific biomarkers related to non-genotoxic cocarcinogenesis was investigated. Several CYP-dependent reactions /were/ ... studied in liver, kidney and lung microsomes derived from male and female Swiss Albino CD1 mice treated i.p. with single (200 or 400 mg/kg b.w.) or repeated (200 mg/kg b.w., 3 days) administrations of fungicide. No significant changes in absolute or relative liver, kidney and lung weights were observed after metalaxyl treatment. Although a single dose did not significantly affect the ... monooxygenases, ... selective CYP3A induction was recorded in different tissues after repeated treatment. An approximately 3-fold increase in CYP3A isozymes ... was observed in the liver (both sexes)... and an approximately 5-fold increase (averaged between male and female) in this oxidase activity was present in the kidney. No significant change of the selected biomarkers was observed in the lung. A weak, but significant reduction of CYP2B1... in liver (male) was also recorded. Liver and kidney CYP3A overexpression was corroborated by means of Western immunoblotting analysis... Northern blotting analysis with CYP3A cDNA biotinylated probe showed that, in the liver, the expression of this isozyme is regulated at the mRNA level. On the whole, these data seem to indicate the cotoxic and cocarcinogenic potential of this fungicide. ... the action of ... /metalaxyl/ on nucleic acid and protein synthesis in liquid cultures of Phytophthora nicotianae /was investigated/. The uptake of 32P, 3H-uridine, 3H-thymidine and 14C-leucine as precursors of nuclei acid and protein synthesis by the mycelium was not inhibited by metalaxyl. RNA synthesis as indicated by 3H-uridine incorporation was strongly inhibited (about 80%) by 0.5 ug/ml of metalaxyl. The inhibition was visible already a few minutes after addition of the toxicant. Since the inhibition of incorporation of 3H-thymidine into DNA and of 14C-leucine into protein became significant 2-3 hours later, ... metalaxyl primarily interferes with RNA synthesis. Synthesis of ribosomal RNA is more affected (more than 90%) than that of tRNA (about 55%) and poly(A)-containing RNA. ...it is also evident that mRNA synthesis is less strongly inhibited, at least during the early period of metalaxyl action. The molecular mechanism of metalaxyl inhibition of the transcription process remains open. The fungicide did not inhibit the activity of a partially purified RNA polymerase isolated from the fungus. On the other hand, the RNA synthesis (14C-UTP-incorporation) by a cell homogenate and by isolated nuclear fractions was inhibited significantly. Possibilities of the molecular action of metalaxyl are discussed. The RNA synthesis of some plant systems (cell cultures of Lycopersicon peruvianum, isolated nuclei from the same cell cultures, purified RNA polymerase from Spinacia oleracea chloroplasts) was not inhibited by metalaxyl, not even at high concentrations. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~250 mg/mL (~895.00 mM) |
| 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 | 3.5800 mL | 17.9000 mL | 35.7999 mL | |
| 5 mM | 0.7160 mL | 3.5800 mL | 7.1600 mL | |
| 10 mM | 0.3580 mL | 1.7900 mL | 3.5800 mL |