70931-18-9Relevant academic research and scientific papers
TRICYCLIC NEUROLEPTICS: SYNTHESIS OF METABOLITES OF ISOFLOXYTHEPIN AND SOME RELATED COMPOUNDS
Sindelar, Karel,Jilek, Jiri,Pomykacek, Josef,Valenta, Vladimir,Hrubantova, Marta,et al.
, p. 2282 - 2303 (2007/10/02)
The isofloxythepin(I) metabolite IV was synthesized via the acids IX and XI and the esters X and XII.The enamine VIII was prepared from 3-fluoro-8-(2-propyl)dibenzothiepin-10(11H)-one by two methods and was reduced to I.Cloflumide (II) was obtained by reaction of 2,10-dichloro-7-fluoro-10,11-dihydrodibenzothiepin with 3-(1-piperazinyl)propionamide and was oxidized to the sulfoxide XVI.The unsaturated analogue XVII of clopithepin (III) was prepared from 2-chlorodibenzothiepin-10(11H)-one by reaction with 2-bromoethanol in the presence of 4-toluenesulfonic acid in boiling benzene and by the following substitution reaction with 2-(1-piperazinyl)ethanol.An improved synthesis of 6-methyldibenzothiepin-10(11H)-one (XIX) was elaborated.The acid XXVII was synthesized and cyclized with polyphosphate ester.A mixture of compounds was formed from which the ketone XXXVI was isolated and processed by reaction with formamide and formic acid at 200 deg C.One of the products was characterized as the formamide XXXIII and was reduced with lithium aluminium hydride to a basic product supposed to be XXXIV.A series of by-products was isolated and characterized.The enamine VIII (VUFB-17156) was found to be a strong neuroleptic agent, similar to isofloxythepin (I).The enol ether XVII (VUFB-17733) was characterized as a mild, practically noncataleptic neuroleptic agent.
FLUORINATED TRICYCLIC NEUROLEPTICS WITH PROLONGED ACTION: 7-FLUORO-11--2-ISOPROPYL-10,11-DIHYDRODIBENZOTHIEPIN
Protiva, Miroslav,Jilek, Jiri,Rajsner, Miroslav,Pomykacek, Josef,Ryska, Miroslav,et al.
, p. 698 - 722 (2007/10/02)
Substitution reaction of 11-chloro-7-fluoro-2-isopropyl-10,11-dihydrodibenzothiepin with 1-(2-hydroxyethyl)piperazine gave the title compound I which proved a very potent and long acting oral neuroleptic agent ("isofloxythepin").Its resolution by means of dibenzoyl-(+)- and (-)-tartaric acid led to (-)- and (+)-enantiomer out of which the former represents the neuroleptically active component.In the synthetic sequence leading to I, preparation of two key intermediates was re-elaborated using new partial sequences: 4-fluoro-2-iodobenzoic acid (XIII) from 4-fluoro-2-nitroaniline (V) via the nitrile VI and the acids VIII and XII, and acetic acid (XVIII) from XIII via XIV and the compounds XV-XVII.The sulfoxides and N-oxides XIX-XXII were prepared as potential metabolites of isofloxithepin (I).
3 Fluoro-10-piperazino-8-substituted 10,11-dihydrodibenzo-(bf) thiepins and method for the preparation thereof
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, (2008/06/13)
Techniques for the preparation of 3-fluoro-10-piperazino-8-substituted 10,11-dihydrodibenzo-(b,f) thiepins and their addition salts with organic and inorganic acids are disclosed. The described compositions evidence psychotropic activity and low toxicity and are characterized as neuroliptics with a high degree of cataleptic, anti-apomorphine and central depressant action.
