Doxylamine

Basic Info

Common NameDoxylamine(F05453)
2D Structure
Description

Histamine H1 antagonist with pronounced sedative properties. It is used in allergies and as an antitussive, antiemetic, and hypnotic. Doxylamine has also been administered in veterinary applications and was formerly used in parkinsonism. [PubChem]

FRCD IDF05453
CAS Number469-21-6
PubChem CID3162
FormulaC17H22N2O
IUPAC Name

N,N-dimethyl-2-(1-phenyl-1-pyridin-2-ylethoxy)ethanamine

InChI Key

HCFDWZZGGLSKEP-UHFFFAOYSA-N

InChI

InChI=1S/C17H22N2O/c1-17(20-14-13-19(2)3,15-9-5-4-6-10-15)16-11-7-8-12-18-16/h4-12H,13-14H2,1-3H3

Canonical SMILES

CC(C1=CC=CC=C1)(C2=CC=CC=N2)OCCN(C)C

Isomeric SMILES

CC(C1=CC=CC=C1)(C2=CC=CC=N2)OCCN(C)C

WikipediaDoxylamine
Synonyms
        
            doxylamine
        
            469-21-6
        
            Doxylaminum
        
            Dossilamina
        
            Doxilminio
        
            Dossilamina [DCIT]
        
            Doxylaminum [INN-Latin]
        
            Doxilminio [INN-Spanish]
        
            Doxylamine [INN:BAN]
        
            Unisom
Classifies
                

                  
                    Predicted: Pesticide
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassBenzenoids
ClassBenzene and substituted derivatives
SubclassBenzylethers
Intermediate Tree NodesNot available
Direct ParentBenzylethers
Alternative Parents
Molecular FrameworkAromatic heteromonocyclic compounds
SubstituentsBenzylether - Pyridine - Heteroaromatic compound - Tertiary amine - Tertiary aliphatic amine - Azacycle - Organoheterocyclic compound - Ether - Dialkyl ether - Amine - Organic oxygen compound - Organooxygen compound - Organonitrogen compound - Organic nitrogen compound - Organopnictogen compound - Hydrocarbon derivative - Aromatic heteromonocyclic compound
DescriptionThis compound belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).

Properties

Property NameProperty Value
Molecular Weight270.376
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count3
Rotatable Bond Count6
Complexity276
Monoisotopic Mass270.173
Exact Mass270.173
XLogP2.5
Formal Charge0
Heavy Atom Count20
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9491
Human Intestinal AbsorptionHIA+0.9505
Caco-2 PermeabilityCaco2+0.7460
P-glycoprotein SubstrateSubstrate0.7449
P-glycoprotein InhibitorNon-inhibitor0.5123
Non-inhibitor0.8383
Renal Organic Cation TransporterInhibitor0.7507
Distribution
Subcellular localizationMitochondria0.6133
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8153
CYP450 2D6 SubstrateNon-substrate0.5432
CYP450 3A4 SubstrateSubstrate0.6801
CYP450 1A2 InhibitorNon-inhibitor0.9092
CYP450 2C9 InhibitorNon-inhibitor0.8957
CYP450 2D6 InhibitorInhibitor0.8361
CYP450 2C19 InhibitorNon-inhibitor0.8764
CYP450 3A4 InhibitorNon-inhibitor0.6894
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.7360
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.8765
Inhibitor0.5398
AMES ToxicityNon AMES toxic0.9133
CarcinogensNon-carcinogens0.9183
Fish ToxicityLow FHMT0.9306
Tetrahymena Pyriformis ToxicityLow TPT0.5473
Honey Bee ToxicityLow HBT0.7557
BiodegradationNot ready biodegradable1.0000
Acute Oral ToxicityIII0.5613
Carcinogenicity (Three-class)Warning0.5274
Model Value Unit
Absorption
Aqueous solubility-2.1409LogS
Caco-2 Permeability1.4493LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.9218LD50, mol/kg
Fish Toxicity1.5608pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.3649pIGC50, ug/L

Targets

Target Details

Histamine H1 receptor

General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
Target Details

Muscarinic acetylcholine receptor M1

General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
Target Details

Nuclear receptor subfamily 1 group I member 3

General Function:
Zinc ion binding
Specific Function:
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element.
Gene Name:
NR1I3
Uniprot ID:
Q14994
Molecular Weight:
39942.145 Da
References
  1. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [20869355 ]