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The preparation of some aminosulphones and related compounds as potential pharmacological agents.

Sax, Philip. (1973) The preparation of some aminosulphones and related compounds as potential pharmacological agents. Doctoral thesis, University of Surrey (United Kingdom)..

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The grouping X-(CH[2])[n] -N< is frequently found in pharmacodynamic agents, where X is OR, OH or O=C-O. By replacing X with sulphone and other sulphur-containing groups it was hoped to obtain novel substances with potential biological activity. The four groups of compounds prepared are depicted below:[chemical equation] - Most of the benzhydryl piperazine derivatives (l) were prepared by reacting the respective N'-benzhydrylpiperazine with the halogen-containing side-chain in a high boiling-point alcohol and in the presence of sodium carbonate. The sulphone (1X=SO[2]) and ether (1,X=0) groups produced the most active antihistamines, with the sulphoxides (1,X=SO) and thioethers (1,X=S) approximately equiactive. Pharmacological tests indicated that a straight chain of a certain minimum length is necessary for protection against histamine induced bronchospasm. Most of the n-fluorobutyrophenones (2,n=3) were prepared from the corresponding N'-gamma-(p-fluorobenzoyl)propylpiperazine and the halogen-containing side-chain. Either the ketone function was protected as a ketal or alternatively a hydrocarbon solvent was used. None of the compounds was an effective muscle relaxant. The ethylsulphone (2,n=3, XR=SO[2]Et) appeared to be the most active. All the p-fluoropropiophenone piperazines (2,n=2) were prepared by the Mannich reaction from the monosubstituted piperazine and p-fluoracetophenone. These propiophenones (2,n=2) appeared to be less active than the butyrophenones (2,n=3). Comparison of the activity of the butyrophenones and propiophenones slows some parallelismexists between the sulphones and the ethers of both series. [chemical equation] The chromans (3,n=1) and coumarans (3,n=0) were all prepared by reacting an aminomethyl heterocycle (5) with the corresponding. halosulphone or haloether. The 2-aminomethylchroman was prepared by a novel route from the previously unreported 2-hydroxymethylchroman and 2-chloromethylchroman. The 3-aminomethylchroman was prepared in a novel manner by the LiAlH[4] reduction in ether of 2H-chromene- 3-carboxamide. The pharmacological results indicated that whether X was SO[2] or O there was a common decreasing order of muscle relaxant activity: benzodioxane, 2-chroman, 3-chroman and coumaran. No correlation was observed between the muscle-relaxant activity of the compounds and their UV absorption characteristics. The Leuckart reaction was used for preparing the phenyltaurines (4;n=0, m=1, R=OH). The key reaction in the preparation of phenyl-GABA sulphones (4;n,m=1, R=Me) was the Micheal addition of a -sulphonyl esters to nitrostyrenes. The novel a-nitrosulphones were hydrogenated to sulphopyrrolidones (6). [chemical equation] None of the taurines, the phenyl-GABA sulphones or the sulphopyrrolidones were biologically active.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
Sax, Philip.
Date : 1973
Contributors :
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1973.
Depositing User : EPrints Services
Date Deposited : 22 Jun 2018 14:26
Last Modified : 06 Nov 2018 16:53

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