Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: Synthesis of 11-(dimethylaminoalkyl) derivatives of 11H-dibenzo[b,e]-1,4-dioxepin and 11H-dibenzo[b,e]-1,4-dithiepin

1982 ◽  
Vol 47 (1) ◽  
pp. 72-87 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Holubek ◽  
Miroslav Ryska ◽  
Emil Svátek ◽  
Antonín Dlabač ◽  
...  
Keyword(s):  
Liquid Ammonia ◽  
Sodium Hydride ◽  
Central Ring ◽  
Simultaneous Formation ◽  
Alternative Synthesis ◽  
Psychotropic Agents ◽  
Reserpine Hypothermia ◽  
The One ◽  
High Degree ◽  
Derivatives Of

1-[2-(2-Fluorophenoxy)phenyl]-4-dimethylaminobutanol (XI) was synthesized from 2-(2-fluorophenoxy)benzoic acid (VIII) in three steps and cyclized with sodium hydride in dimethylformamide to the title compound V. Reaction of 5-chloro-2-(methylthio)thiophenol (XIV) with sodium and liquid ammonia afforded benzene-1,2-dithiol (XIII) which was treated with 2-bromobenzyl bromide and gave 11H-dibenzo[b,e]-1,4-dithiepin (II). An alternative synthesis of compound II consisted in the cyclization of 2-(2-bromophenylthiomethyl)thiophenol (XVIII) and was accompanied by the simultaneous formation of 6H, 12H-dibenzo[b,f]-1,5-dithiocin (XIX) and thianthrene (XX). Reaction of compound II with n-butyllithium and the following treatment with dimethylaminoalkyl chlorides or with carbon dioxide resulted on the one hand in two further title compounds VI and VII, and in the carboxylic acid XXI on the other. 2-Chloro-11H-dibenzo[b,e]-1,4-dithiepin (XXII) was obtained by a further synthesis alternative using in the first step the cyclization of 2-(4-chloro-2-chloromethylphenylthio)thiophenol (XXV). Compound VI and VII showed a high degree of activity in the test of antagonization of reserpine hypothermia in mice.

Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: 8-Substituted 6-(4-piperidyl)-6H-dibenz[b,e]-1,4-oxathiepins

1982 ◽  
Vol 47 (11) ◽  
pp. 3077-3093 ◽  
Author(s):  
Karel Šindelář ◽  
Jiřina Metyšová ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Jiří Protiva ◽  
...  
Keyword(s):  
Secondary Amine ◽  
Amino Alcohol ◽  
Sodium Hydride ◽  
Amino Alcohols ◽  
Central Ring ◽  
Psychotropic Agents ◽  
High Degree ◽  
By Products ◽  
Antiapomorphine Effect ◽  
Central Depressant

2-(2-Fluorophenylthio)benzaldehydes IXa-c and 5-chloro-2-(2-fluorophenylthio)acetophenone were treated with 1-methyl-4-piperidylmagnesium chloride and 3-dimethylaminopropylmagnesium chloride, respectively, and the resulting amino alcohols VIa-c, XVII and XVIII were cyclized with sodium hydride in dimethylformamide. In addition to the title compounds Ia-c, XIX and XX, several types of by-products were obtained. Demethylation of compound Ib by the chloroformate method afforded the secondary amine IIb which was transformed to the amino alcohols IIIb and Vb. Compounds Ia-c are very potent neuroleptics with a high degree of central depressant and cataleptic activity. The amino alcohol Vb exhibits a very strong antiapomorphine effect in rats.

Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: Derivatives of 11H-dibenz[b,f]-1,4-oxathiepin

1982 ◽  
Vol 47 (3) ◽  
pp. 967-983 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Holubek ◽  
Miroslav Ryska ◽  
Antonín Dlabač ◽  
Jiřina Metyšová ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Sodium Hydride ◽  
Sulfuryl Chloride ◽  
Side Chains ◽  
Central Ring ◽  
Lithium Compounds ◽  
Psychotropic Agents ◽  
Trifluoromethyl Derivative ◽  
Derivatives Of

Reactions of 2-bromobenzyl bromide and its analogues XVII and XXV with 2-hydroxythiophenol resulted in 11H-dibenz[b,f]-1,4-oxathiepin (Ia) and its 2-chloro (Ib) and 2-trifluoromethyl derivative (IC). Treatment of the lithium compounds derived from Ia and Ib with carbon dioxide and dimethylaminoalkyl chlorides gave compounds IIa, Va and VIab; modification of side chains led to amines IVa, VIIa and VIIIa. 11-(1-Methyl-4-piperidyl) derivatives Xbc were obtained by chlorination of compounds Ibc with sulfuryl chloride or N-chlorosuccinimide and the following treatment with 1-methyl-4-piperidylmagnesium chloride. Compound Ib was transformed by oxidation to the sulfone XX affording by treatment with sodium hydride and tert-aminoalkylchlorides the basic sulfones XXI and XXII. While the nuclearly unsubstituted amines with the aliphatic side chains (IVa and VIIa) have intensive antireserpine activity and are potential antidepressants, the 11-(1-methyl-4-piperidyl) derivatives with a substituent in position 2 of the skeleton (Xbc) are potential neuroleptics; the trifluoromethyl derivative Xc especially has outstanding cataleptic and antiapomorphine efficacy.

Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: 2-Fluoro-8-substituted 6-(4-piperidyl)-6H-dibenz[b,e]-1,4-oxathiepins

1982 ◽  
Vol 47 (11) ◽  
pp. 3114-3133 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Miroslav Ryska ◽  
Antonín Dlabač ◽  
...  
Keyword(s):  
Sodium Hydroxide ◽  
Sodium Hydride ◽  
Central Ring ◽  
Highly Active ◽  
Psychotropic Agents ◽  
Triethylbenzylammonium Chloride ◽  
Depot Neuroleptic ◽  
Boron Tribromide ◽  
Long Acting ◽  
By Products

The aldehydes VIa and VIb were transformed by treatment with chloroform and sodium hydroxide in the presence of triethylbenzylammonium chloride to the α-chloro acids VIIa and VIIb which were demethylated with boron tribromide and the products were cyclized with sodium hydroxide in dimethyl sulfoxide to 2-fluoro-6H-dibenz[b,e]-1,4-oxathiepin-6-carboxylic acids Ia and Ib. Syntheses of the aldehydes XVIIbcd were carried out and the products treated with 1-methyl-4-piperidylmagnesium chloride to give the amino alcohols XVIbcd. Cyclizations with sodium hydride in dimethylformamide afforded the title compounds XIIbcd; compounds XVIIIbc and XIX were isolated as by-products and characterized. Compound XIIb was transformed via the secondary amine XIIIb to the amino alcohol XIVb which was esterified to the decanoate XVb. Substances XIIbcd are highly active neuroleptic agents with an important prolongation of the central depressant effect. The decanoate XVb revealed the properties of a medium long acting depot neuroleptic.

Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: Synthesis of 6-(aminoalkyl) derivatives of 6H-dibenz[b,e]-1,4-oxathiepin

1982 ◽  
Vol 47 (5) ◽  
pp. 1367-1381 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Miroslav Ryska ◽  
Antonín Dlabač ◽  
...  
Keyword(s):  
Dimethyl Sulfoxide ◽  
Sodium Hydroxide ◽  
Benzyl Bromide ◽  
Sodium Hydride ◽  
Aqueous Sodium Hydroxide ◽  
Aqueous Sodium ◽  
Psychotropic Agents ◽  
Triethylbenzylammonium Chloride ◽  
Boron Tribromide ◽  
Derivatives Of

Heating of 2-(2-hydroxyphenylthio)benzoic acid (XX) with acetic anhydride gave dibenz[b,e]-1,4-oxathiepin-6-one (XXII). Demethylation of 2-(2-methoxyphenylthio)benzyl bromide (XI) with boron tribromide and the following treatment with aqueous sodium hydroxide in dimethyl sulfoxide afforded 6H-dibenz[b,e]-1,4-oxathiepin (I) which was halogenated with chlorine or N-bromosuccinimide only to the undesirable 2-halogeno derivatives II and III. A reaction of 2-(2-methoxyphenylthio)benzaldehyde (XII) with chloroform and 50% aqueous sodium hydroxide in the presence of triethylbenzylammonium chloride led to the α-chloro acid XIX whose demethylation with boron tribromide and the following cyclization with sodium hydroxide in dimethyl sulfoxide gave a mixture with prevailing 6H-dibenz[b,e]-1,4-oxathiepin-6-carboxylic acid (IV). Amino alcohols XXV-XXVIII were obtained by reactions of 2-(2-fluorophenylthio)benzaldehyde (XXIV) with the corresponding Grignard reagents and the products were cyclized with sodium hydride in dimethylformamide to the title compounds V-VIII. While compounds V and VI showed antireserpine effects and can be considered as potential antidepresants, compound VIII has a strong central depressant activity, brings about ataxia, hypothermia and potentiates the cataleptic action of neuroleptics (properties of a tranquillizer).

El Prestige: comparativa de los regímenes internacionales de responsabilidad civil

2019 ◽  
Vol 37 (3) ◽  
pp. 31
Author(s):  
Raquel Fernández González ◽  
Marcos Íñigo Pérez Pérez
Keyword(s):  
Institutional Economics ◽  
Geographical Area ◽  
New Institutional Economics ◽  
Rigorous Analysis ◽  
Judicial Process ◽  
Main Research ◽  
Civil Responsibility ◽  
The One ◽  
High Degree ◽  
The Prestige

The return of institutions to the main research agenda has highlighted the importance of rules in economic analysis. The New Institutional Economics has allowed a better understanding of the case studies that concern different areas of knowledge, also the one concerning the management of natural resources. In this article, the institutional analysis focuses on the maritime domain, where two large civil liability regimes for pollution coexist (OPA 90-IMO), each in a different geographical area (United States - Europe). Therefore, a comparative analysis is made between the two large regimes of civil responsibility assignment applying them to the Prestige catastrophe. In this way, the allocation and distribution of responsibilities in the investigation and subsequent judicial process of the Prestige is compared with an alternative scenario in which the applicable compensation instruments are governed by the provisions of the Oil Polution Act of 1990 (OPA 90), in order to establish a rigorous analysis on the effects that the different norms can have in the same scenario. In the comparative established in the case of the Prestige, where the responsibilities were solved very slowly in a judicial process with high transaction costs, the application of rules governed by the OPA 90 would not count with such a high degree of imperfection. This is so, since by applying the preponderance of the evidence existing in OPA 90 there would be no mitigation for the presumed culprits. On the other hand, the agents involved in the sinking would not be limited only to the owner, but also that operators or shipowners would be responsible as well. In addition, the amount of compensation would increase when counting in the damage count the personal damages, the taxes without perceiving and the ecological damage caused in a broad sense, damages not computable in the IMO.

New Psychotropic Agents.1II. Derivatives of 5,6-Dihydrodibenz[b,e]azepine (5,6-Dihydromorphanthridine)

1962 ◽  
Vol 5 (6) ◽  
pp. 1199-1206 ◽  
Author(s):  
Stanley O. Winthrop ◽  
M. A. Davis ◽  
F. Herr ◽  
J. Stewart ◽  
Roger. Gaudry
Keyword(s):  
Psychotropic Agents ◽  
Derivatives Of
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