87848-99-5 Usage
Description
Different sources of media describe the Description of 87848-99-5 differently. You can refer to the following data:
1. Acrivastine is an orally-active HI .receptor antagonist reportedly useful in the treatment of
allergic rhinitis. The main advantages of acrivastine in comparison to older antihistamines
are its low sedative potential and the absence of anticholinergic side-effects.
2. Acrivastine is a histamine H1 receptor antagonist with a Ki value of 10 nM in COS-7 cells expressing the human receptor. In vivo, acrivastine (1 mg/kg) completely inhibits response to histamine in guinea pigs. Formulations containing acrivastine have been used for the treatment of seasonal allergies and hay fever.
Originator
Burroughs Wellcome (USA)
Uses
Different sources of media describe the Uses of 87848-99-5 differently. You can refer to the following data:
1. Antihistaminic.
2. Acrivastine has been used as an antihistamine to investigate the relation between the increased residence time of antihistamine at the histamine H1 receptor (H1R) and the duration of effective target-inhibition by this antagonist.
Definition
ChEBI: A member of the class of pyridines that is (pyridin-2-yl)acrylic acid substituted at position 6 by a [(1E)-1-(4-methylphenyl)-3-(pyrrolidin-1-yl)prop-1-en-1-yl group. It is a non-sedating antihistamine used for treatment of hayfever, urtic
ria, and rhinitis.
Manufacturing Process
Butyl lithium (50 ml, 1.65 mol in hexane) was added under nitrogen to a
stirred suspension of 2,6-dibromopyridine (19.5 g) in dry ether (200 ml) at -
50°C. After 0.75 h a solution of 4-tolunitrile (10.0 g) in ether (50 ml) was
added; stirring was continued at -50°C for 3 h. The mixture was allowed to
warm to -30°C and treated with hydrochloric acid (200 ml, 2 mol). The
precipitated solid was collected, washed with water to give the 2-bromo-6-(4-
toluoyl)pyridine as colourless needles (12.2 g), melting point 97°-98°C
(recrystallized from aqueous ethanol).
A mixture of 2-bromo-6-(4-toluoyl)pyridine (200.0 g), ethylene glycol (85 ml),
p-toluenesulphonic acid (32.0 g) and benzene (11 ml) was boiled under a
Dean/Stark trap until water collection had become very slow (about 20 ml
collected in 16 h).
The cooled solution was poured into ice/water containing sodium carbonate
(100.0 g) with stirring. The benzene layer was separated, washed with water,
dried with sodium sulfate and evaporated to about 500 ml. Cooling gave a first crop of 2-(6-bromo-2-pyridyl)-2-(4-tolyl)-1,3-dioxolan, melting point
113°-114°C (170.0 g). Dilution with petroleum ether gave a second crop,
melting point 109°-112°C (34.0 g). The residue after evaporation (31.0 g)
was recycled.
A solution of 2-(6-bromo-2-pyridyl)-2-(4-tolyl)-1,3-dioxolan, vide supra, (70.0
g) in dry toluene (800 ml) was added dropwise during 5 h to a stirred solution
of butyl lithium (1.6 mol in hexane, 200 ml) and toluene (200 ml) at -65° to -
72°C under nitrogen. After a further 30 min at -70°C, dry dimethylformamide
(40 ml) was added during 35 min. Stirring continued overnight at -70° to -
60°C. Hydrochloric acid (2 N, 400 ml) was added, allowing the temperature to
rise to about -10°C. After 30 min, 2 N ammonia (ca. 90 ml) was added to pH
7-8. The toluene layer was separated and the aqueous phase was extracted
with ether. The combined organic liquids were washed with ice/water, dried
(MgSO4) and evaporated in vacuum below 50°C. The aldehyde, 2-(6-formyl-2-
pyridyl)-2-(4-tolyl)-1,3-dioxolan, (63.9 g) crystallized on keeping at 3°C,
melting point 52-63°C.
The 2-(6-formyl-2-pyridyl)-2-(4-tolyl)-1,3-dioxolan (2.5 g) was dissolved in
1,2-dimethoxyethane (10 ml) and added to a solution of the phosphonate
carbanion produced from triethyl phosphonoacetate (2.0 g) and sodium
hydride (0.22 g) in the same solvent. The mixture was stirred for 2 h, diluted
with ether (25 ml) and treated with hydrochloric acid (5 ml, 2 mol). The
organic phase was separated, washed with water, dried, and evaporated. The
resulting oil was dissolved in ethanol (20 ml) containing concentrated
hydrochloric acid (3 ml) and water (3 ml). After heating on the steam bath for
10 min, the solution was diluted with ice water, rendered alkaline with sodium
bicarbonate solution, and extracted with ether. Evaporation gave 1.0 g ((E)-3-
(6-(4-toluoyl)-2-pyridyl)acrylate as colourless platelets, melting point 108°-
111°C (crystallized from cyclohexane).
Butyl lithium (10 ml, 1.64 mol in hexane) was added under nitrogen to a
stirred suspension of triphenyl-2-pyrrolidinoethylphosphonium bromide (7.2 g)
in dry toluene (75 ml). After 0.5 h, ((E)-3-(6-(4-toluoyl)-2-pyridyl)acrylate,
vide supra, (4.8 g) in toluene (50 ml) was added. The suspension, initially
orange, became deep purple, then slowly faded to yellow during 2 h heating
at 75°C. The cooled solution was diluted with ether (150 ml) and treated with
hydrochloric acid (50 ml, 2 mol). The aqueous phase was separated, washed
with ether, and basified with potassium carbonate (ice) and extracted with
ether. The mixture of isomeric esters obtained by evaporation was dissolved in
ethanol (100 ml) containing sodium hydroxide solution (20 ml, 1 mol) and
partially evaporated on the steam bath under reduced pressure for 5 min. The
residual aqueous solution was neutralized with sulfuric acid (20 ml, 0.5 mol)
and evaporated to dryness. The solid residue was extracted with hot
isopropanol (3x50 ml) and the extracts were concentrated until crystallization
commenced. The (E)-3-(6-(3-pyrrolidino-1-(4-tolyl)prop-1-(E)-enyl)-2-
pyridyl)acrylic acid, melting point 222°C (dec. recrystallization from
isopropanol) was obtained.
Brand name
Semprex
Therapeutic Function
Antihistaminic
General Description
Acrivastine, (E, E)-3-[6-[1-(4-methylphenyl)-3-(1-pyrrolidinyl)-1-propenyl-2-pyridinyl]-2-propenoic acid(Semprex), is a fixed-combination product of the antihistamineacrivastine (8 mg) with the decongestant pseudoephedrine(60 mg). Acrivastine is an odorless, white to pale cream crystallinepowder that is soluble in chloroform and alcohol andslightly soluble in water.Acrivastine is an analog of triprolidine containing acarboxyethenyl moiety at the 6-position of the pyridylring. Acrivastine shows antihistaminic potency and durationof action comparable to those of triprolidine (Table23.2). Unlike triprolidine, acrivastine does not display significantanticholinergic activity at therapeutic concentrations.Also, the enhanced polarity of this compound resultingfrom carboxyethenyl substitution limits BBBaccumulation, and thus, this compound produces less sedationthan triprolidine.Limited pharmacokinetic data are available for this compound.Orally administered drug has a half-life of about 1.7hours and a total body clearance of 4.4 mL/min per kilogram.The mean peak plasma concentrations are reported tovary widely, and the drug appears to penetrate the CNSpoorly. The metabolic fate of acrivastine has not beenreported.
Biochem/physiol Actions
Acrivastine is a second-generation antihistamine, an H1-receptor antagonist.
Clinical Use
Acrivastine, an acidic congener of triprolidine in which a carboxylic acid–substituted chain
has been attached, also is a second-generation, nonsedating antihistamine. Penetration of
the blood-brain barrier is limited, and it is less sedating than triprolidine. It is used principally
in a combination with a decongestant.
Metabolism
Acrivastine undergoes metabolism in the liver, and along
with an active metabolite, is excreted principally in the
urine.
Check Digit Verification of cas no
The CAS Registry Mumber 87848-99-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,7,8,4 and 8 respectively; the second part has 2 digits, 9 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 87848-99:
(7*8)+(6*7)+(5*8)+(4*4)+(3*8)+(2*9)+(1*9)=205
205 % 10 = 5
So 87848-99-5 is a valid CAS Registry Number.
InChI:InChI=1/C22H24N2O2/c1-17-7-9-18(10-8-17)20(13-16-24-14-2-3-15-24)21-6-4-5-19(23-21)11-12-22(25)26/h4-13H,2-3,14-16H2,1H3,(H,25,26)/b12-11+,20-13+
87848-99-5Relevant articles and documents
Chromatographic separation and spectroscopic characterization of the E/Z isomers of acrivastine
Davadra, Prakash M.,Dabhi, Batuk,Singh, Manoj K.,Jain, Mukul R.,Joshi, Hitendra S.,Bapodra, Atul H.
, p. 955 - 960 (2011)
A reverse phase high performance liquid chromatography (HPLC) method has been developed for the separation of two geometric isomers of Acrivastine using crude reaction mixture. The resolution between two isomers was found more than 2.9. The geometric isomers have been isolated by preparative HPLC and characterized by spectroscopic techniques, such as NMR, infrared, and MS. The developed method has been validated for the determination of Z-isomer in Acrivastine. The limit of detection and limit of quantification of the Z-isomer were 0.05 and 0.2 μg/ml, respectively. The developed method is precise, linear, accurate, rugged and robust for its intended use.
Method for preparing acrivastine
-
Paragraph 0041-0041, (2017/05/18)
The invention belongs to the field of pharmaceutical synthesis, and relates to a method for preparing acrivastine. The method comprises the steps of adopting an acriva ethyl ester compound as a raw material, dissolving the acriva ethyl ester compound into an organic solvent medium, adding an inorganic base for alkaline hydrolysis, and completing alkaline reaction to obtain a hydrolysate of the acriva ethyl ester compound; decompressing concentrating the hydrolysate of the acriva ethyl ester compound until stopping flowing, and obtaining a concentrate; and adding water into the obtained concentrate, cooling to be ranged from 20 DEG C to 30 DEG C, acidizing to enable pH (Potential of Hydrogen) to be ranged from 5.0 to 7.0, crystallizing through a temperature differential method, filtering and drying to obtain an acrivastine crude product. The method is simple to operate, low in cost, free of using an organic solvent, environmentally friendly and easy for industrial production, and the obtained acrivastine is high in yield, high in purity and stable in quality.
Triprolidine radioimmunoassay: Disposition in animals and humans
Findlay,Butz,Coker,et al.
, p. 1339 - 1344 (2007/10/02)
A hapten derivative of triprolidine, bearing an acrylic acid side chain ortho to the pyridine ring nitrogen atom, was synthesized and coupled to bovine serum albumin. Immunization of New Zealand White rabbits with the resulting drug-protein conjugate resulted in the production of antisera capable of binding a radioiodinated tyramine conjugate of the triprolidine hapten derivative at high antiserum dilutions (1:70,000-1:150,000). These antisera were used to develop a radioimmunoassay (RIA) for triprolidine in human plasma with a sensitivity limit of 0.1 ng/mL (0.01 ng of actual mass). The known hydroxymethyl and carboxyl metabolites of triprolidine cross-reacted weakly (2 and 0.05%, respectively) with this antiserum. The RIA could be used for the direct analysis of triprolidine in human and rabbit plasma, but not for rat or dog plasma, presumably due to the presence of other interfering substances (possibly metabolites). The validity of the RIA procedure in human plasma was demonstrated by comparative analysis of a number of samples by quantitative TLC (r = 0.985, slope = 1.076). The assay was employed to describe the pharmacokinetics of triprolidine in the rabbit (t( 1/2 ,β) = 1.7 h). The assay had adequate sensitivity to detect low circulating drug concentrations in humans after therapeutic oral doses and also substantiated previous disposition experiments with triprolidine in humans (t( 1/2 ,β = 2.27 h). TLC analysis demonstrated that the absolute oral bioavailability of triprolidine (1-mg/kg dose) in the dog was low (4%). A comparison of triprolidine pharmacokinetic parameters in dogs, rabbits, rats, and human revealed considerable similarity in elimination characteristics in these species.
