1-bromo-3-chloro-5,5-dimethylhydantoin

General Information

Mainterm	1-bromo-3-chloro-5,5-dimethylhydantoin
CAS Reg.No.(or other ID)	16079-88-2
Regnum

From www.fda.gov

Computed Descriptors

Download SDF

2D Structure
CID	61828
IUPAC Name	1-bromo-3-chloro-5,5-dimethylimidazolidine-2,4-dione
InChI	InChI=1S/C5H6BrClN2O2/c1-5(2)3(10)8(7)4(11)9(5)6/h1-2H3
InChI Key	PIEXCQIOSMOEOU-UHFFFAOYSA-N
Canonical SMILES	CC1(C(=O)N(C(=O)N1Br)Cl)C
Molecular Formula	C5H6BrClN2O2
Wikipedia	1-bromo-3-chloro-5,5-dimethyl-2,4-imidazolidinedione

From Pubchem

Computed Properties

Property Name	Property Value
Molecular Weight	241.469
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	0
Complexity	231.0
CACTVS Substructure Key Fingerprint	A A A D c Y B j M A A E E A A A A A A A A A A A A A A A A W A A A A A A A A A A A A A A A A A A A A A A H g A A M A A A D I i B g A A D A A I A A A A I A A E Q E A A A A A A A A A A A A A G A A A C A Q A A A A C A U A A A I B S I A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area	40.6
Monoisotopic Mass	239.93
Exact Mass	239.93
XLogP3	None
XLogP3-AA	1.3
Compound Is Canonicalized	True
Formal Charge	0
Heavy Atom Count	11
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

From Pubchem

ADMET Predicted Profile --- Classification

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.9782
Human Intestinal Absorption	HIA+	0.9967
Caco-2 Permeability	Caco2-	0.5088
P-glycoprotein Substrate	Non-substrate	0.7631
P-glycoprotein Inhibitor	Non-inhibitor	0.7552
P-glycoprotein Inhibitor	Non-inhibitor	0.9883
Renal Organic Cation Transporter	Non-inhibitor	0.9278
Distribution
Subcellular localization	Mitochondria	0.7954
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.7261
CYP450 2D6 Substrate	Non-substrate	0.8305
CYP450 3A4 Substrate	Non-substrate	0.5359
CYP450 1A2 Inhibitor	Non-inhibitor	0.7948
CYP450 2C9 Inhibitor	Non-inhibitor	0.7342
CYP450 2D6 Inhibitor	Non-inhibitor	0.9111
CYP450 2C19 Inhibitor	Non-inhibitor	0.5238
CYP450 3A4 Inhibitor	Non-inhibitor	0.8451
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.9108
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9401
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9187
AMES Toxicity	Non AMES toxic	0.8864
Carcinogens	Non-carcinogens	0.7438
Fish Toxicity	High FHMT	0.6475
Tetrahymena Pyriformis Toxicity	High TPT	0.9684
Honey Bee Toxicity	Low HBT	0.7810
Biodegradation	Not ready biodegradable	0.9616
Acute Oral Toxicity	III	0.5182
Carcinogenicity (Three-class)	Non-required	0.4870

From admetSAR

ADMET Predicted Profile --- Regression

Model	Value	Unit
Absorption
Aqueous solubility	-2.8507	LogS
Caco-2 Permeability	1.3674	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.6658	LD50, mol/kg
Fish Toxicity	2.1797	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.7044	pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of Exposure	Oral ; inhalation ; dermal
Mechanism of Toxicity	BCDMH likely causes tissue irritation through its breakdown products (hypochlorous acid and hypobromous acid) which, on their own, can cause local irritation. 5,5-dimethylhydantoin is also produced spontaneously from BCDMH decomposition and hydantoins are also known to be allergens.
Metabolism	Spontaneously reacts with water releasing hypochlorous acid and hypobromous acid along with 5,5-dimethylhydantion.
Toxicity Values	LD50: 1390 mg/kg (Oral, Rat) LD50: >2000 mg/kg (Dermal, Rabbit)
Lethal Dose
Carcinogenicity (IARC Classification)	No indication of carcinogenicity (not listed by IARC).
Minimum Risk Level
Health Effects	Corrosive. Acute exposure causes irreversible eye damage and skin burns. Eye contact may cause loss of vision. Irritating to nose and throat and may be fatal if large quantities are inhaled. Harmful if absorbed through skin or swallowed. Can cause contact dermatitis through exposure in swimming pools. It is not carcinogenic or mutagenic.
Treatment	EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.
Reference	Penny PT: Contact dermatitis due to BCDMH in a hydrotherapy pool. Occup Med (Lond). 1999 May;49(4):265-7.[10474922 ] Li W, Wei J, Jin H, Huang M, Zhang J, Li C, Chen C, Liu C, Wang A: Study of the toxicity of 1-Bromo-3-chloro-5,5-dimethylhydantoin to zebrafish. Biomed Environ Sci. 2011 Aug;24(4):383-90. doi: 10.3967/0895-3988.2011.04.009.[22108327 ] Dalmau G, Martinez-Escala ME, Gazquez V, Pujol-Montcusi JA, Canadell L, Espona Quer M, Pujol RM, Vilaplana J, Gaig P, Gimenez-Arnau A: Swimming pool contact dermatitis caused by 1-bromo-3-chloro-5,5-dimethyl hydantoin. Contact Dermatitis. 2012 Jun;66(6):335-9. doi: 10.1111/j.1600-0536.2012.02030.x.[22568840 ]

From T3DB

Taxonomic Classification

Kingdom	Organic compounds
Superclass	Organoheterocyclic compounds
Class	Azolidines
Subclass	Imidazolidines
Intermediate Tree Nodes	Imidazolidinones - Imidazolidinediones
Direct Parent	Hydantoins
Alternative Parents	Organopnictogen compounds Alpha amino acids and derivatives Organic oxides Dicarboximides Hydrocarbon derivatives Organic carbonic acids and derivatives Organonitrogen compounds Carbonyl compounds Azacyclic compounds
Molecular Framework	Aliphatic heteromonocyclic compounds
Substituents	Hydantoin - Alpha-amino acid or derivatives - Dicarboximide - Carbonic acid derivative - Azacycle - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Carbonyl group - Aliphatic heteromonocyclic compound
Description	This compound belongs to the class of organic compounds known as hydantoins. These are heterocyclic compounds containing an imidazolidine substituted by ketone group at positions 2 and 4.

From ClassyFire

Targets

Target Details

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

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. [23611293 ]

Target Details

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

Wikipedia. BCDMH. Last Updated 20 May 2009. : http://en.wikipedia.org/wiki/BCDMH [22568840 ]

Target Details

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

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. [16531984 ]

From T3DB