The effect of aromatic substitution on neuroleptic activity in 1-piperazino-3-phenylindans. A comparison based on a new D-2 receptor model with corresponding 10-piperazino-10,11-dihydrodibenzo[b,f]thiepins

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Title:The effect of aromatic substitution on neuroleptic activity in 1-piperazino-3-phenylindans. A comparison based on a new D-2 receptor model with corresponding 10-piperazino-10,11-dihydrodibenzo[b,f]thiepins
Creators:
Bøgesø, Klaus P.
Sommer, Michael Bech
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 56, 11, pp. 2456-2467

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.

Title:The effect of aromatic substitution on neuroleptic activity in 1-piperazino-3-phenylindans. A comparison based on a new D-2 receptor model with corresponding 10-piperazino-10,11-dihydrodibenzo[b,f]thiepins
Creators:
Bøgesø, Klaus P.
Sommer, Michael Bech
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:56
Number:11
Page Range:pp. 2456-2467
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19912456UNSPECIFIED
ID Code:5177
Item Type:Article
Deposited On:22 Feb 2010 11:32
Last Modified:22 Feb 2010 10:32

Citation

Bøgesø, Klaus P.; Sommer, Michael Bech (1991) The effect of aromatic substitution on neuroleptic activity in 1-piperazino-3-phenylindans. A comparison based on a new D-2 receptor model with corresponding 10-piperazino-10,11-dihydrodibenzo[b,f]thiepins. Collection of Czechoslovak Chemical Communications, 56 (11). pp. 2456-2467. ISSN 0010-0765

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