Synthesis and histamine H2-antagonist activity of 4-quinazolinone derivatives.
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Ogawa,Yoshida,Aratani,Koshinaka,Kato,Ito
p. 2955 - 2967
(2007/10/02)
FLUORINATED TRICYCLIC NEUROLEPTICS WITH PROLONGED ACTION: 7-FLUORO-11--2-ISOPROPYL-10,11-DIHYDRODIBENZOTHIEPIN
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).