34580-13-7 Usage
Originator
Zaditen,Wander,Switz.,1978
Uses
Different sources of media describe the Uses of 34580-13-7 differently. You can refer to the following data:
1. Anti-asthmatic.
2. Ketotifen is an intermediate in the synthesis of Ketotifen N-Oxide Hydrochloride (K315410), which is a metabolite of Ketotifen (K315100) in humans; formed by human liver microsome. For the free base, see K315115.
Manufacturing Process
3.07 g of iodine-activated magnesium shavings are covered with a layer of 25
cc of tetrahydrofuran, and approximately 1/10 of a solution of 17.7 g of 4-
chloro-1-methylpiperidine base in 70 cc of absolute tetrahydrofuran is added.
The Grignard reaction is initiated by the addition of a few drops of 1,2-
dibromoethane. The remaining 4-chloro-1-methylpiperidine solution is then
added dropwise to the magnesium at such a rate that the reaction mixture
boils continuously at reflux without external heating. Boiling at reflux is then
continued for 1 hour. 15.3 g of 10-methoxy-4H-benzo[4,5]cyclohepta[1,2-
b]thiophen-4-one are subsequently added portionwise at 20°C, within 40
minutes, with slight cooling. After stirring at 20°C for 1,5 hours, the reaction
solution is poured on a mixture of 180 g of ice and 20 g of ammonium
chloride. The free base is extracted with chloroform.The chloroform solution is concentrated and the residue recrystallized from
270 cc of absolute ethanol. The pure 10-methoxy-4-(1-methyl-4-piperidyl)-
4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ol base, having a melting point of
194°C to 196°C, is obtained in this manner. Microanalysis corresponds with
the formula C20H23NO2S.A mixture of 3.4 g of 10-methoxy-4-(1-methyl-4-piperidyl)-4H-benzo[4,5]
cyclohepta [1,2-b]thiophen-4-ol base and 40 cc of 3N hydrochloric acid is kept
in a boiling water bath at 95°C to 100°C for 1 hour. The mixture is
subsequently made alkaline with concentrated caustic soda solution at 20°C
while cooling, and the free base is extracted with chloroform. The chloroform
solution is concentrated, and the residue is recrystallized from ethanol/water
1:1. The pure 4-(1-methyl-4-piperidylidene)-4H-benzo[4,5]cyclohepta [1,2-b]
thiophen-10(9H)-one base, having a melting point of 152°C to 153°C, is
obtained in this manner.
Therapeutic Function
Anti-asthmatic, Antihistaminic
General Description
Crystals (from ethyl acetate).
Fire Hazard
Flash point data for KETOTIFEN are not available. KETOTIFEN is probably combustible.
Clinical Use
Ketotifen is a potent, selective H1 antihistamine that also prevents release of transmitters
from mast cells. It is approved in the United States for topical use to prevent itching of the
eye because of allergic conjunctivitis, It is used as a systemic antiallergy agent in several
countries outside the United States for the treatment of seasonal allergic rhinitis, hay fever,
and asthma. Being structurally analogous to the cyproheptadine-like antihistamines,
differences in activity of the two enantiomers (atropisomers) has been noted, being
approximately six- to seven-fold in ligand displacement and rodent-based assays.
Ketotifen has been shown to stabilize mast cells and to inhibit degranulation of eosinophils.
Like olopatadine, it has been shown to interact with model membranes, stabilizing them by
interaction with phospholipids monolayers.
Metabolism
Undergoes hepatic first-pass metabolism to form inactive
metabolites which are mainly excreted in the urine
Check Digit Verification of cas no
The CAS Registry Mumber 34580-13-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,4,5,8 and 0 respectively; the second part has 2 digits, 1 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 34580-13:
(7*3)+(6*4)+(5*5)+(4*8)+(3*0)+(2*1)+(1*3)=107
107 % 10 = 7
So 34580-13-7 is a valid CAS Registry Number.
InChI:InChI=1S/C19H19NOS/c1-20-9-6-13(7-10-20)18-15-5-3-2-4-14(15)12-17(21)19-16(18)8-11-22-19/h2-5,8,11H,6-7,9-10,12H2,1H3
34580-13-7Relevant articles and documents
4H-BENZOCYLOHEPTATHIOPHENES AND 9,10-DIHYDRO DERIVATIVES-SULFONIUM ANALOGUES OF PIZOTIFEN AND KETOTIFEN; CHIRALITY OF KETOTIFEN: SYNTHESIS OF THE 2-BROMO DERIVATIVE OF KETOTIFEN
Polivka, Zdenek,Budesinsky, Milos,Holubek, Jiri,Schneider, Bohdan,Sediva, Zdenek,et al.
, p. 2443 - 2469 (2007/10/02)
Reaction of ketone IX with 4-tetrahydrothiopyranylmagnesium bromide and the following dehydration with thionyl chloride afforded the sulfide III which was transformed to the methiodide II (sulfonium analogue of pizotifen).Similar sequence starting from ketone XXIV and concluded by dehydration of the alcohol XX, cleavage of the enol ether, and by treatment with methyl iodide resulted in the formation of the sulfonium analogue of ketotifen (V).Three modified routes leading to ketotifen (IV) are being described.The chirality of ketotifen was proven by (1)H NMR spectrscopy with the help of,optically active NMR shift reagent.The resolution of racemic ketotifen (IV) was achieved by crystallization of salts with optically active O,O'-diacyltartaric acids and homogenous anantiomers were obtained.The X-ray crystallographic analysis of (+)-IV-O,O'-di(p-toluoyl)-(R)-tartrate led to the three- dimensional structure of the molecule of (+)-ketotifen which enabled to determine its absolute configuration to be (R).One of the products of bromination of the ketone IX, the following methanolysis and dehydrobromonation, identified as XXVII, was transformed by reaction with 1-methyl-4-piperidylmagnesium chloride, by the following acid-catalyzed dehydration, and cleavage of the enol ether to the 2-bromo derivative of ketotifen XXXIV. (R)(+)-Ketotifen (IV) was found to be the more active ketotifen enantiomer but the stereoselectivity of its action is only a partial one.The 2-bromo derivative of ketotifen (XXXIV) is much less active than ketotifen in the line antihistamine activity.
