Fexofenadine

Basic Info

Common NameFexofenadine(F04773)
2D Structure
Description

Fexofenadine is an antihistamine drug used in the treatment of hayfever and similar allergy symptoms. It was developed as a successor of and alternative to terfenadine, an antihistamine with potentially fatal contraindications. Fexofenadine, like other second-generation antihistamines, does not readily enter the brain from the blood, and so causes less drowsiness than first generation histamine receptor antagonists; Fexofenadine hydrochloride (brand names include Allegra and Telfast) is an antihistamine drug used in the treatment of hayfever and similar allergy symptoms. It was developed as a successor of and alternative to terfenadine, an antihistamine with potentially fatal contraindications. Fexofenadine, like other second generation antihistamines, does not readily enter the brain from the blood, and so causes less drowsiness than first-generation histamine-receptor antagonists.

FRCD IDF04773
CAS Number83799-24-0
PubChem CID3348
FormulaC32H39NO4
IUPAC Name

2-[4-[1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoic acid

InChI Key

RWTNPBWLLIMQHL-UHFFFAOYSA-N

InChI

InChI=1S/C32H39NO4/c1-31(2,30(35)36)25-17-15-24(16-18-25)29(34)14-9-21-33-22-19-28(20-23-33)32(37,26-10-5-3-6-11-26)27-12-7-4-8-13-27/h3-8,10-13,15-18,28-29,34,37H,9,14,19-23H2,1-2H3,(H,35,36)

Canonical SMILES

CC(C)(C1=CC=C(C=C1)C(CCCN2CCC(CC2)C(C3=CC=CC=C3)(C4=CC=CC=C4)O)O)C(=O)O

Isomeric SMILES

CC(C)(C1=CC=C(C=C1)C(CCCN2CCC(CC2)C(C3=CC=CC=C3)(C4=CC=CC=C4)O)O)C(=O)O

WikipediaFexofenadine
Synonyms
        
            Carboxyterfenadine
        
            Fexofenadine [INN:BAN]
        
            fexofenadine
        
            83799-24-0
        
            Terfenadine carboxylate
        
            Terfenadine-COOH
        
            Terfenadine acid metabolite
        
            Allegra
        
            Fexofendine
        
            MDL 16455
Classifies
                

                  
                    Predicted: Pesticide
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassBenzenoids
ClassBenzene and substituted derivatives
SubclassDiphenylmethanes
Intermediate Tree NodesNot available
Direct ParentDiphenylmethanes
Alternative Parents
Molecular FrameworkAromatic heteromonocyclic compounds
SubstituentsDiphenylmethane - Phenylbutylamine - Phenylpropane - Aralkylamine - Piperidine - Tertiary alcohol - Amino acid or derivatives - Secondary alcohol - Amino acid - Tertiary amine - Tertiary aliphatic amine - Azacycle - Organoheterocyclic compound - Carboxylic acid derivative - Carboxylic acid - Monocarboxylic acid or derivatives - Hydrocarbon derivative - Organic oxygen compound - Organooxygen compound - Organonitrogen compound - Organopnictogen compound - Organic nitrogen compound - Organic oxide - Amine - Carbonyl group - Aromatic alcohol - Alcohol - Aromatic heteromonocyclic compound
DescriptionThis compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.

Properties

Property NameProperty Value
Molecular Weight501.667
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count5
Rotatable Bond Count10
Complexity678
Monoisotopic Mass501.288
Exact Mass501.288
XLogP3
Formal Charge0
Heavy Atom Count37
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-0.8574
Human Intestinal AbsorptionHIA+0.7881
Caco-2 PermeabilityCaco2+0.5000
P-glycoprotein SubstrateSubstrate0.8641
P-glycoprotein InhibitorNon-inhibitor0.6791
Non-inhibitor0.8779
Renal Organic Cation TransporterNon-inhibitor0.5166
Distribution
Subcellular localizationMitochondria0.8430
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8360
CYP450 2D6 SubstrateNon-substrate0.9116
CYP450 3A4 SubstrateSubstrate0.6458
CYP450 1A2 InhibitorNon-inhibitor0.9046
CYP450 2C9 InhibitorNon-inhibitor0.9162
CYP450 2D6 InhibitorNon-inhibitor0.9231
CYP450 2C19 InhibitorNon-inhibitor0.9026
CYP450 3A4 InhibitorNon-inhibitor0.8421
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9756
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.8469
Inhibitor0.6258
AMES ToxicityNon AMES toxic0.9122
CarcinogensNon-carcinogens0.9163
Fish ToxicityHigh FHMT0.5628
Tetrahymena Pyriformis ToxicityHigh TPT0.9205
Honey Bee ToxicityLow HBT0.7170
BiodegradationNot ready biodegradable0.8428
Acute Oral ToxicityIII0.6841
Carcinogenicity (Three-class)Non-required0.6577
Model Value Unit
Absorption
Aqueous solubility-2.1011LogS
Caco-2 Permeability0.7444LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.3481LD50, mol/kg
Fish Toxicity2.0396pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.1526pIGC50, ug/L

References

TitleJournalDatePubmed ID
Selected Food/Herb-Drug Interactions: Mechanisms and Clinical Relevance.Am J Ther2018 Jul/Aug29232282

Targets

Target Details

Potassium voltage-gated channel subfamily H member 2

General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
References
  1. Rajamani R, Tounge BA, Li J, Reynolds CH: A two-state homology model of the hERG K+ channel: application to ligand binding. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1737-41. [15745831 ]
Target Details

Histamine H4 receptor

General Function:
Histamine receptor activity
Specific Function:
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).
Gene Name:
HRH4
Uniprot ID:
Q9H3N8
Molecular Weight:
44495.375 Da
References
  1. Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R: Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther. 2005 Sep;314(3):1310-21. Epub 2005 Jun 9. [15947036 ]
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
Mechanism of Action:
Like other H1-blockers, Fexofenadine competes with free histamine for binding at H1-receptors in the GI tract, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Fexofenadine exhibits no anticholinergic, alpha1-adrenergic or beta-adrenergic-receptor blocking effects.
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]