50679-08-8 Usage
Description
Terfenadine is a non-sedating, first-generation H1 antihistamine medication. It functions as a histamine H1-receptor antagonist, effectively blocking the action of histamine in the body. Terfenadine is known for its antihistaminic properties and is commonly used to alleviate various allergic symptoms. It is a white solid and is marketed under brand names such as Antifen and Fenadin.
Uses
Used in Pharmaceutical Industry:
Terfenadine is used as an antihistaminic agent for treating symptoms associated with seasonal allergic rhinitis and conjunctivitis. It helps in providing relief from angioneurotic edema and allergic skin reactions, as well as being a component of complex therapy for bronchial asthma.
Used in Research and Development:
In the field of research, Terfenadine has been utilized to study the role of histamine in itch related to proteinase-activated receptors (PARs) in mice. Additionally, it has been employed to block histamine receptor type 1, aiding in the investigation of the pathogenesis of 2,4-dinitrobenzene sulfonic acid (DNBS)-induced ulcerative colitis in rats.
Originator
Histafen,Berk
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.
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, α-(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).
Check Digit Verification of cas no
The CAS Registry Mumber 50679-08-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,0,6,7 and 9 respectively; the second part has 2 digits, 0 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 50679-08:
(7*5)+(6*0)+(5*6)+(4*7)+(3*9)+(2*0)+(1*8)=128
128 % 10 = 8
So 50679-08-8 is a valid CAS Registry Number.
InChI:InChI=1/C32H41NO2/c1-31(2,3)26-18-16-25(17-19-26)30(34)15-10-22-33-23-20-29(21-24-33)32(35,27-11-6-4-7-12-27)28-13-8-5-9-14-28/h4-9,11-14,16-19,29-30,34-35H,10,15,20-24H2,1-3H3/p+1/t30-/m1/s1
50679-08-8Relevant articles and documents
METHODS AND COMPOSITIONS FOR TREATING INFECTION
-
Paragraph 0210; 0223, (2015/09/28)
Provided herein are compositions and methods for treating or preventing infection.
Identification of terfenadine as an inhibitor of human CD81-receptor HCV-E2 interaction: Synthesis and structure optimization
Holzer, Marcel,Ziegler, Sigrid,Albrecht, Beatrice,Kronenberger, Bernd,Kaul, Artur,Bartenschlager, Ralf,Kattner, Lars,Klein, Christian D.,Hartmann, Rolf W.
, p. 1081 - 1110 (2008/09/21)
Terfenadine (4-[4-(hydroxydiphenylmethyl)-1-piperidyl]-1-(4-tert- butylphenyl)-butan-1-ol) was identified in a biological screening to be a moderate inhibitor (27 % inhibition) of the CD81-LEL-HCV-E2 interaction. To increase the observed biological activity, 63 terfenadine derivates were synthesized via microwave assisted nucleophilic substitution. The prepared compounds were tested for their inhibitory potency by means of a fluorescence labeled antibody assay using HUH7.5 cells. Distinct structure-activity relationships could be derived. Optimization was successful, leading to 3g, identfied as the most potent compound (69 % inhibition). Experiments with viral particles revealed that there might be additional HCV infection reducing mechanisms.
Process and diastereomeric salts useful for the optical resolution of racemic a-[4- (1,1-dimethylethy) phenyl) -4- (hydroxydipenylmethyl) -1-piperidinebutanol and derivative compounds
-
, (2008/06/13)
A process and diastereomeric salts useful for the optical resolution of racemic alpha-[4-(1,1-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol, 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic acid and lower alkyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetates. The process comprises placing into solution a chiral resolving agent, either (+)/(-)-di-paratoluoyltartaric acid or (-)/(+)-mandelic acid, in an amount equimolar to a compound corresponding to the desired enantiomer of the above compound, precipitating the resulting diastereomeric salt between the chiral resolving agent and the target enantiomer and separating the enantiomer.
