diphenylpyraline

Diafen,Riker,US,1955

Diphenylpyraline is an H1 receptor antagonist (an antihistamine), and is commonly prescribed to treat allergic and vasomotor rhinitis. There is also some research being conducted on diphenylpyraline derivatives to determine their antimycobacterial and antifungal activity.

ChEBI: Diphenylpyraline is a member of the class of piperidines that is the benzhydryl ether derivative of 1-methyl-4-hydroxypiperidine. A sedating antihistamine, it is used as the hydrochloride for the symptomatic relief of allergic conditions including rhinitis and hay fever, and in pruritic skin disorders. It is also used as the teoclate salt (piprinhydrinate) as an ingredient in compound preparations for the symptomatic relief of coughs and the common cold. It has a role as a H1-receptor antagonist and a cholinergic antagonist. It is a member of piperidines and a tertiary amine.

Diphenylpyraline synthesis via coupling of 4-hydroxy-1-methylpiperidine with benzhydrylbromide.

A mixture of 46 grams of 1-methyl-4-piperidinol (0.4 mol), 49.4 grams of benzhydryl
omide (0.2 mol) and 100 ml of xylene was refluxed for approximately 24 hours. The reaction mixture separated into two phases with the upper phase containing the desired ether compound dissolved in xylene. The lower phase consisted of the hydro
omide salt of the excess 1-methyl-4- piperidinol. The upper phase was separated from the lower phase and the desired benzhydryl ether recovered in the crude state by distilling off the xylene under reduced pressure.
The crude benzhydryl ether was a clear reddish oil. It was dissolved in 75 ml of 20% hydrochloric acid and the aqueous acid solution then washed three times with 50 ml portions each of ethyl ether. The aqueous acid solution was then decolorized with activated carbon and thereafter slowly admixed with 75 ml of 28% aqueous ammonia. The benzhydryl ether separated as an oily material and was removed from the aqueous mixture by extraction with three 50 ml portions of ethyl ether.
On evaporation of the ethyl ether from the ethyl ether solution, the benzhydryl ether was recovered as a pale yellow oil. The benzhydryl ether was dissolved in 60 ml of isopropanol and the isopropanol solution acidified to a pH of 3 with dry hydrogen chloride-methanol solution. The acidic propanol solution was then diluted with ethyl ether until a faint turbidity was observed. In a short time, the crystalline hydrochloride salt of the benzhydryl ether separated from the propanol solution. The crystallized salt was recrystallized once from 75 ml of isopropanol with the aid of ethyl ether in order to further purify the material. A yield of the pure hydrochloride salt of 1-methylpiperidyl- 4-benzhydryl ether of 24.5 grams was obtained. This was 39% of the theoretical yield. The pure material had a melting point of 206°C.

Antihistaminic

Antihistamines such as diphenylpyraline used in the treatment of allergy act by competing with histamine for H1-receptor sites on effector cells. This reduces the effects of histamine, leading to a temporary reduction of allergy symptoms.

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[2] P. RAMAPPA K. G S. Synthesis and Characterization of Copper(II) Complexes with Diphenylpyraline Hydrochloride[J]. Synthesis and Reactivity in Inorganic and Metal-organic Chemistry, 1998, 21 1: 263-274. DOI:10.1080/00945719809351902.
[3] ROBERT WEIS Werner S Andreas J Kungl. Synthesis of new analogues of diphenylpyraline[J]. Tetrahedron, 2003, 59 9: Pages 1403-1411. DOI:10.1016/S0040-4020(03)00072-3.