Showing papers by "Klaus Peter Bogeso published in 1991"
TL;DR: In this paper, the validity of a new dopamine D2 receptor interaction model based on conformational analysis and least squares superimposition studies of the indan derivative tefludazine and the thiepin derivative octoclothepin was further tested by comparison of the effect of aromatic substitution on D-2 antagonistic activity.
Abstract: The validity of a new dopamine D-2 receptor interaction model based on conformational analysis and least-squares superimposition studies of the indan derivative tefludazine and the thiepin derivative octoclothepin was further tested by comparison of the effect of aromatic substitution on D-2 antagonistic activity in two series of indan and thiepin derivatives. The indan series include new derivatives substituted in the 4-, 7-, 2’- and 3’-position. The substitution effects were largely parallel with one important exception: Only 6-substituted indans have significant neuroleptic activity while both 8- and 7-substituted thiepin derivatives have neuroleptic activity. In indans additional fluorination in the 2’- or 4’-position is demanded to give potent neuroleptic activity, while a 3’-fluoro-substituted derivative was inactive. Fluorination is not necessary in thiepins although 3-fluoro derivatives have a significant prolonged duration of action. Considering the differences in physico-chemical properties, metabolism and pharmacokinetics between the two series, the largely parallel substitution effects support the new D-2 receptor model.
3 citations
Patent•
[...]
28 Nov 1991
TL;DR: In this article, trans-1-piperazino-indane substitution in position 5 is defined as a substitution in the formule generale, where the trans- 1iperazinine is replaced by a trans-2-phenylene eventuellement.
Abstract: Derives de trans-1-piperazino-indane a substitution en position 5 ayant la formule generale (I) ou X est halogene, trifluoromethyle, alkyle, alkylthio, alkyloxy, hydroxy, alkylsulphonyle, alkyl- ou dialkylamino, trifluoromethylthio ou cyano; R est hydrogene, ou alkyle, alcenyle, cycloalkyle, ou alkyle cycloalkyle inferieur, eventuellement substitue par hydroxy, ou R est un substituant (a) ou n est un nombre entier compris entre 1 et 6; U est CH ou N; Y est CH2, O, S, ou N-R1, R1 etant hydrogene ou cycloalkyle, cycloalkylmethyle, alkyle ou alcenyle eventuellement substitue par hydroxy ou un groupe phenyle eventuellement substitue; W est O ou S; Z est -(CH?2?)4-, (b), (c) ou R?2 et R3? sont hydrogene ou un alkyle inferieur, -CH=CH-, -CH=CH-CH?2?-, 1,2-phenylene eventuellement substitue, 1,2-C6H4CH2- (pour former un compose cyclique quinazolidinone ou -thione) ou 1,2-C6H4CO- (pour former un compose cyclique quinazolidindione ou thioxoquinazolidinone); et Ar est un compose cyclique phenyle, thiophene ou furane eventuellement substitue. Ces derives sont des antagonistes selectifs de 5-HT2 agissant principalement sur le systeme nerveux central, utiles dans le traitement de l'anxiete, de la depression, des troubles du sommeil et des symptomes negatifs de la schizophrenie ou de la migraine.