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Record Information
Version2.0
Creation Date2009-06-17 23:53:05 UTC
Update Date2014-12-24 20:23:01 UTC
Accession NumberT3D0994
Identification
Common NamePhenmedipham
ClassSmall Molecule
DescriptionPhenmedipham is a selective herbicide of the carbanilate and biscarbamate classes. Carbamate pesticides are derived from carbamic acid and kill insects in a similar fashion as organophosphate insecticides. They are widely used in homes, gardens and agriculture. The first carbamate, carbaryl, was introduced in 1956 and more of it has been used throughout the world than all other carbamates combined. Because of carbaryl's relatively low mammalian oral and dermal toxicity and broad control spectrum, it has had wide use in lawn and garden settings. Most of the carbamates are extremely toxic to Hymenoptera, and precautions must be taken to avoid exposure to foraging bees or parasitic wasps. Some of the carbamates are translocated within plants, making them an effective systemic treatment. Phenmedipham was developed by Schering AG and approved for use in the United States in 1970. Today, about 100 tons of Phenmedipham are used each year. It is commonly used in beet, spinach, and strawberry crops to protect against weeds, often in comination with Desmedipham under the trade names Betanal or Betamax. (3)
Compound Type
  • Amine
  • Carbamate
  • Ester
  • Ether
  • Herbicide
  • Organic Compound
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
3-((Methoxycarbonyl)amino)phenyl (3-methylphenyl)carbamate
3-(Carbomethoxyamino)phenyl 3-methylcarbanilate
3-Methoxycarbonyl-N-(3'-methylphenyl)-carbamat
3-Methoxycarbonylaminophenyl 3'-methylcarbanilate
3-Methoxycarbonylaminophenyl N-3'-methylphenylcarbamate
3-[(Methoxycarbonyl)amino]phenyl (3-methylphenyl)carbamate
Alegro
Beetomax
Beetup
BETA
Betaflow
Betalion
Betamix
Betanal
Betanal e
Betanal tandem
Betosip
Caswell No. 648B
Ethofumesate-phenmedipham
Fender
Fenmedifam
Goliath
Gusto
Headland dephend
Kemifam
m-Hydroxycarbanilic acid methyl ester m-methylcarbanilate
Medipham
Methyl 3-(3-methylcarbaniloyloxy)carbanilate
Methyl 3-(m-tolylcarbamoyloxy)phenylcarbamate
Methyl m-hydroxycarbanilate m-methylcarbanilate
Methyl m-hydroxycarbanilate m-methylcarbanilate (ester)
Methyl m-hydroxycarbanilate, m-methylcarbanilate
Methyl-3-(3-methylcarbaniloyloxy) carbanilate
Methyl-3-hydroxycarbanilate-3-methylcarbanilate
Methyl-3-m-tolycarbamoloxyphenyl carbamate
Morton EP 452
Phendipham
Phenmediphame
Pistol
Pistol 400
Protrum k
Schering 4072
Spin-aid
Suplex
Synbetan p
Tripart beta
Tripart beta 2
Vangard
Vanguard
Chemical FormulaC16H16N2O4
Average Molecular Mass300.309 g/mol
Monoisotopic Mass300.111 g/mol
CAS Registry Number13684-63-4
IUPAC Name1-3-{[hydroxy(methoxy)methylidene]amino}phenoxy-N-(3-methylphenyl)methanimidic acid
Traditional Name1-3-{[hydroxy(methoxy)methylidene]amino}phenoxy-N-(3-methylphenyl)methanimidic acid
SMILESCOC(O)=NC1=CC(OC(O)=NC2=CC=CC(C)=C2)=CC=C1
InChI IdentifierInChI=1S/C16H16N2O4/c1-11-5-3-6-12(9-11)18-16(20)22-14-8-4-7-13(10-14)17-15(19)21-2/h3-10H,1-2H3,(H,17,19)(H,18,20)
InChI KeyInChIKey=IDOWTHOLJBTAFI-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylcarbamic acid esters. These are ester derivatives of phenylcarbamic acids.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylcarbamic acid esters
Direct ParentPhenylcarbamic acid esters
Alternative Parents
Substituents
  • Phenylcarbamic acid ester
  • Phenoxy compound
  • Toluene
  • Carbamic acid ester
  • Carbonic acid derivative
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Metabolic PathwaysNot AvailableNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceColorless and odorless powder.
Experimental Properties
PropertyValue
Melting Point143-144 °C
Boiling PointDecomposition at> 200 °C
SolubilityPractically insoluble in water (4.7 mg/L); soluble in polar organic solvents
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.017 g/LALOGPS
logP2.5ALOGPS
logP5.28ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)2.91ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area83.64 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity85.63 m³·mol⁻¹ChemAxon
Polarizability30.77 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-0910000000-f30d7fef5d59b6c5ce93JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_1) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-000i-0900000000-00031c14ca44e9139da9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-014r-0900000000-58c2bf322552cc023a2cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-000i-0900000000-48fd93926a23be06e22fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-000i-0900000000-e0ddaebfe93fd113eec8JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-000i-0900000000-ec1e788887825ffd4f0cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-014i-0900000000-f503ecc696af8c003a6eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-000i-0900000000-73e4c8828d11574f5451JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-014i-0900000000-285f09d3c2697ef6975aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-052r-3900000000-1c4f4f8b000368ac97deJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-06el-8900000000-89453a33a33ec2ad9279JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-000i-1900000000-6a34a96bdb4b2086cd06JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-000i-0900000000-0fbfef39b582949ab789JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-014i-0900000000-aba50b6e242108613201JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-000i-0900000000-6c56388e0bc4b72f9781JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-000i-0900000000-9f94251a5005a58d3751JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-000i-1900000000-308e1ba29a7937090320JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-014r-0900000000-1a043edb4709fa7aad1dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-052r-3900000000-dcc4c2258728e16c13a9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-06el-8900000000-1ec41aa995a5fb8c1e67JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0gb9-0915000000-63d6e03ed88c54642817JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-0910000000-29a9b44697d8a365aa4aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00m0-2900000000-9af527c638cac566c742JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00lr-0960000000-7f9c2c8524e4108413e5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00lr-0930000000-35b7fc9406bb7cece661JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-0900000000-b8bb1126db209fc546e1JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-00lr-5900000000-18214c4b9332b3821a3eJSpectraViewer | MoNA
Toxicity Profile
Route of ExposureInhalation (2) ; oral (2); dermal (2)
Mechanism of ToxicityPhenmedipham is a cholinesterase or acetylcholinesterase (AChE) inhibitor. Carbamates form unstable complexes with chlolinesterases by carbamoylation of the active sites of the enzymes. This inhibition is reversible. A cholinesterase inhibitor suppresses the action of acetylcholine esterase. Because of its essential function, chemicals that interfere with the action of acetylcholine esterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses. Headache, salivation, nausea, vomiting, abdominal pain and diarrhea are often prominent at higher levels of exposure. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop.
MetabolismThe carbamates are hydrolyzed enzymatically by the liver; degradation products are excreted by the kidneys and the liver. (2)
Toxicity ValuesLD50: >8000 mg/kg (Rat, oral)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesPhenmedipham is a selective herbicide commonly used in beet, spinach, and strawberry crops to protect against weeds, often in comination with Desmedipham.
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Chronically high (>10 years) exposure leads to neuropsychological consequences including disturbances in perception and visuo-motor processing. (1)
SymptomsAs with organophosphates, the signs and symptoms are based on excessive cholinergic stimulation. Unlike organophosphate poisoning, carbamate poisonings tend to be of shorter duration because the inhibition of nervous tissue acetylcholinesterase is reversible, and carbamates are more rapidly metabolized. Muscle weakness, dizziness, sweating and slight body discomfort are commonly reported early symptoms. Headache, salivation, nausea, vomiting, abdominal pain and diarrhea are often prominent at higher levels of exposure. Contraction of the pupils with blurred vision, incoordination, muscle twitching and slurred speech have been reported. (3)
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID24744
ChEMBL IDCHEMBL1079421
ChemSpider ID23134
KEGG IDC18420
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDCPD-6967
CTD IDC100128
Stitch IDPhenmedipham
PDB IDNot Available
ACToR ID6509
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Roldan-Tapia L, Nieto-Escamez FA, del Aguila EM, Laynez F, Parron T, Sanchez-Santed F: Neuropsychological sequelae from acute poisoning and long-term exposure to carbamate and organophosphate pesticides. Neurotoxicol Teratol. 2006 Nov-Dec;28(6):694-703. Epub 2006 Aug 30. [17029710 ]
  2. IPCS Intox Database (1987). Antimony pentoxide. [Link]
  3. Fishel F (2009). Pesticide Toxicity Profile: Carbamate Pesticides. University of Florida, IFAS Extension. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
References
  1. Fishel F (2009). Pesticide Toxicity Profile: Carbamate Pesticides. University of Florida, IFAS Extension. [Link]
General Function:
Identical protein binding
Specific Function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
BCHE
Uniprot ID:
P06276
Molecular Weight:
68417.575 Da
References
  1. Fishel F (2009). Pesticide Toxicity Profile: Carbamate Pesticides. University of Florida, IFAS Extension. [Link]
General Function:
Fatty acid amide hydrolase activity
Specific Function:
Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates.
Gene Name:
FAAH
Uniprot ID:
O00519
Molecular Weight:
63065.28 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.152 uMNot AvailableBindingDB 50311785
IC500.377 uMNot AvailableBindingDB 50311785
References
  1. Vincent F, Nguyen MT, Emerling DE, Kelly MG, Duncton MA: Mining biologically-active molecules for inhibitors of fatty acid amide hydrolase (FAAH): identification of phenmedipham and amperozide as FAAH inhibitors. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6793-6. doi: 10.1016/j.bmcl.2009.09.086. Epub 2009 Sep 30. [19850474 ]
General Function:
Transcription regulatory region dna binding
Specific Function:
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
Gene Name:
AHR
Uniprot ID:
P35869
Molecular Weight:
96146.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.43 uMTox21_AhRTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.26 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]