Taziprinone (T3D2378)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (4)XML
Targets (4)
Record Information
Version2.0
Creation Date2009-06-24 20:58:50 UTC
Update Date2014-12-24 20:25:26 UTC
Accession NumberT3D2378
Identification
Common NameTaziprinone
ClassSmall Molecule
DescriptionChlorinated dibenzofurans (CDFs) are a family of chemical that contain one to eight chlorine atoms attached to the carbon atoms of the parent chemical, dibenzofuran. The CDF family contains 135 individual compounds (known as congeners) with varying harmful health and environmental effects. Of these 135 compounds, those that contain chlorine atoms at the 2,3,7,8-positions of the parent dibenzofuran molecule are especially harmful. Other than for laboratory use of small amounts of CDFs for research and development purposes, these chemicals are not deliberately produced by industry. Most CDFs are produced in very small amounts as unwanted impurities of certain products and processes utilizing chlorinated compounds. Only a few of the 135 CDF compounds have been produced in large enough quantities so that their properties, such as color, smell, taste, and toxicity could be studied. (4)
Compound Type
  • Amide
  • Amine
  • Aromatic Hydrocarbon
  • Dibenzofuran
  • Ether
  • Industrial By-product/Pollutant
  • Industrial/Workplace Toxin
  • Lachrymator
  • Organic Compound
  • Pesticide
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
N-[(4R,4aR,9bS)-8,9b-dimethyl-3-oxo-1,2,4,4a-tetrahydrodibenzofuran-4-yl]-3-(4-methylpiperazin-1-yl)propanamide
Chemical FormulaC22H31N3O3
Average Molecular Mass385.500 g/mol
Monoisotopic Mass385.237 g/mol
CAS Registry Number79253-92-2
IUPAC NameN-{2,12-dimethyl-5-oxo-8-oxatricyclo[7.4.0.0²,⁷]trideca-1(13),9,11-trien-6-yl}-3-(4-methylpiperazin-1-yl)propanamide
Traditional NameN-{2,12-dimethyl-5-oxo-8-oxatricyclo[7.4.0.0²,⁷]trideca-1(13),9,11-trien-6-yl}-3-(4-methylpiperazin-1-yl)propanamide
SMILESCN1CCN(CCC(=O)NC2C3OC4=CC=C(C)C=C4C3(C)CCC2=O)CC1
InChI IdentifierInChI=1S/C22H31N3O3/c1-15-4-5-18-16(14-15)22(2)8-6-17(26)20(21(22)28-18)23-19(27)7-9-25-12-10-24(3)11-13-25/h4-5,14,20-21H,6-13H2,1-3H3,(H,23,27)
InChI KeyInChIKey=IQRFTIWMGLZYTL-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as beta amino acids and derivatives. These are amino acids having a (-NH2) group attached to the beta carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentBeta amino acids and derivatives
Alternative Parents
Substituents
  • Beta amino acid or derivatives
  • Coumaran
  • Alkyl aryl ether
  • N-alkylpiperazine
  • N-methylpiperazine
  • 1,4-diazinane
  • Piperazine
  • Benzenoid
  • Carboxamide group
  • Ketone
  • Secondary carboxylic acid amide
  • Tertiary amine
  • Cyclic ketone
  • Tertiary aliphatic amine
  • Ether
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Organic oxide
  • Organopnictogen compound
  • Carbonyl group
  • Organooxygen compound
  • Amine
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceColorless crystals.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.36 g/LALOGPS
logP1.81ALOGPS
logP1.98ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)12.58ChemAxon
pKa (Strongest Basic)7.9ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area61.88 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity108.59 m³·mol⁻¹ChemAxon
Polarizability44.23 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001r-0197000000-2d62a2a0ad7008f1ec5c2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-1591000000-9ab05cc97dbe89c957672016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00e9-9640000000-8846f06649788743bf382016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0119000000-e56fc3e8f841144ca4652016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001j-7898000000-a1df58c2502a0d96a91e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-9610000000-832c6a4463ef65d533692016-08-03View Spectrum
Toxicity Profile
Route of ExposureInhalation (4) ; dermal (4) ; oral (4)
Mechanism of ToxicityDibenzofurans bind the aryl hydrocarbon receptor, which increases its ability to activate transcription in the XRE promoter region. This alters the expression of a number of genes. (1)
MetabolismNo information on the metabolism of dibenzofuran in mammalian organisms was found in the available literature. The bacteria Sphingomonas, Brevibacterium, Terrabacter, and Staphylococcus auricularis degrade dibenzofuran to 2,2',3-trihydroxybiphenyl via dibenzofuran 4,4a-dioxygenase. (4)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity (not listed by IARC). (3)
Uses/SourcesCDFs are created from production of coal tar and during incineration. They are used as insecticides, in the production of PVC, and in industrial bleaching. (4)
Minimum Risk LevelNot Available
Health EffectsCDFs cause vomiting and diarrhea, anemia, more frequent lung infections, numbness and other effects on the nervous system, and mild changes in the liver. However, there were no permanent liver changes or definite liver damage found in people who ingested CDFs. (4)
SymptomsSkin and eye irritations, especially severe acne, darkened skin color, and swollen eyelids with discharge are the most obvious health effects of the CDF poisoning. (4)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID173619
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDTaziprinone
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Ni J, Pang ST, Yeh S: Differential retention of alpha-vitamin E is correlated with its transporter gene expression and growth inhibition efficacy in prostate cancer cells. Prostate. 2007 Apr 1;67(5):463-71. [17252538 ]
  2. Long G, McKinney J, Pedersen L. Polychlorinated Dibenzofuran (PCDF) Binding to the Ah Receptor(s) and Associated Enzyme Induction. Theoretical Model Based on Molecular Parameters. Quantitative Structure-Activity Relationships. 2002;6(1):1-7.
  3. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  4. Wikipedia. Dibenzofuran. Last Updated 1 June 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Aryl hydrocarbon receptor
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
References
  1. Ni J, Pang ST, Yeh S: Differential retention of alpha-vitamin E is correlated with its transporter gene expression and growth inhibition efficacy in prostate cancer cells. Prostate. 2007 Apr 1;67(5):463-71. [17252538 ]
  2. Long G, McKinney J, Pedersen L. Polychlorinated Dibenzofuran (PCDF) Binding to the Ah Receptor(s) and Associated Enzyme Induction. Theoretical Model Based on Molecular Parameters. Quantitative Structure-Activity Relationships. 2002;6(1):1-7.
Target Details
2. Estrogen receptor
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
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
  2. Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
Target Details
3. Estrogen receptor beta
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
  2. Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
Target Details
4. Transient receptor potential cation channel subfamily A member 1
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]