Terfenadine Property

Melting point:

145-152 °C

Boiling point:

572.76°C (rough estimate)

Density 

1.0488 (rough estimate)

refractive index 

1.6310 (estimate)

storage temp. 

2-8°C

solubility 

chloroform: soluble250 mg plus 5 ml of solvent, clear to very slightly hazy, colorless to faintly yellow

form 

Solid

pka

pKa 9.21(H2O t = 25 I = 0.025) (Uncertain)

color 

White to Off-White

Water Solubility 

0.001 g/100 mL (30 ºC)

CAS DataBase Reference

50679-08-8(CAS DataBase Reference)

NIST Chemistry Reference

Seldane(50679-08-8)

Safety

Safety Statements 

24/25

WGK Germany 

2

RTECS 

TM4969000

HS Code 

29333999

Hazardous Substances Data

50679-08-8(Hazardous Substances Data)

Toxicity

LD50 orally in mice: >2000 mg/kg (Carr, Meyer)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H413May cause long lasting harmful effects to aquatic life

Precautionary statements

P273Avoid release to the environment.

P501Dispose of contents/container to..…

Terfenadine Chemical Properties,Usage,Production

Chemical Properties

White Solid

Originator

Histafen,Berk

Uses

Nonsedating-type histamine H1-receptor antagonist. Antihistaminic

Uses

H1 antihistamine

Uses

It is used for relieving symptoms associated with seasonal allergic rhinitis and conjunctivitis, for angioneurotic edema and allergic skin reaction, and also as an ingredient of complex therapy for bronchial asthma. Synonyms of this drug are seldane, hystadin, trexil, and others.

Uses

Terfenadine has been used to study the role of histamine in itch related to proteinase-activated receptors (PARs) in mice. Terfenadine has also been used to block histamine receptor type 1 to study the pathogenesis of 2,4-dinitrobenzene sulfonic acid (DNBS)-induced ulcerative colitis in rats.

Definition

ChEBI: Terfenadine is a diarylmethane.

Manufacturing Process

A mixture of 107 g (0.4 mole) of α,α-diphenyl-4-piperidinemethanol, 105 g (0.44 mole) of 4'-tert-butyl-4-chlorobutyrophenone, 70 g (0.7 mole) of potassium bicarbonate, and a small amount of potassium iodide in 600 ml of toluene was refluxed and stirred for 2.5 days then filtered. The filtrate was treated with charcoal, filtered through celite then treated with ethereal HCl. The resulting solid was recrystallized from methanol and isopropyl alcohol to give the 4'-tert-butyl-4-[4-(α-hydroxy-α-phenylbenzyl)piperidino]- butyrophenone hydrochloride, melting point 234°-235°C.
To a mixture of 4.2 g (0.0083 mole) of 4'-tert-butyl-4-[4-(α-hydroxy-α- phenylbenzyl)piperidino]-butyrophenone hydrochloride and 0.54 g (0.01 mole) of sodium methoxide in 25 ml of methanol is added 2.16 g (0.04 mole) of potassium borohydride. The reaction mixture is stirred overnight, diluted with water and the methanol removed under reduced pressure. The remaining material is extracted with chloroform, washed with water, dried over magnesium sulfate and filtered. The filtrate is concentrated, and the residue is recrystallized from acetone-water to give 4-[α-(p-tert-butylphenyl)-α- hydroxybenzyl]-α-phenyl-1-piperidinebutanol, melting point 161°-163°C.

brand name

Antifen;Fenadin.

Therapeutic Function

Antihistaminic, Bronchodilator

World Health Organization (WHO)

The first clinically interesting histamine H-receptor1 antagonists were introduced in the late 1940s and early 1950s. Several H-antihistaminics have a similar cardiac effect to that seen with astemizole1 and terfenadine. Serious cardiovascular adverse reactions have been reported when used concomitantly with imidazole antifungals and macrolide antibiotics. See also under astemizole.

Biological Activity

Histamine H 1 receptor antagonist. Also blocks hERG and K ATP channels (IC 50 values are 204 nM and 1.2 μ M respectively). Inhibits the delayed rectifier K + current (I Kr ) in guinea pig ventricular myocytes (IC 50 = 50 nM). Activity prolongs QT and induces Torsades de pointes (TdP); cardiotoxic in vivo .

Biochem/physiol Actions

Non-sedating second generation H1 histamine receptor antagonist. Mainly metabolized by Cyp3A4, 5, 7. Inhibits CYP2C8.

Pharmacology

Terfenadine not only differs from the other antihistamine drugs in its chemical structure, but also in that its action begins within 1–2 h and last approximately 12 h, reaching its peak of action in 3–4 h.

Synthesis

Terfenadine, |á-(4-tert-butylphenyl) -4-hydroxydiphenylmethyl)- 1-piperidinebutanol (16.1.24), is synthesized in two ways. According to the first, benzyl-4- magnesiumchloropiperidine is reacted with benzophenone, giving (1-benzyl-4-piperidyl) diphenylcarbinol (16.2.22), which undergoes further debenzylation by reduction with hydrogen using a palladium over carbon catalyst, giving (4-piperidyl)diphenylcarbinol (16.2.22). This product is alkylated by either 1-(4-tert-butylphenyl)-4-chlorobutanol, which forms terfenadine (16.1.24), or by alkylating with (4-tert-butylphenyl-3-chloropropiophenone, which forms the product (16.1.25), the carbonyl group of which is reduced to an alcohol group, thus giving the desired terfenadine (16.1.24).

storage

Store at +4°C