α-Benzyldopamine and some related compounds: Synthesis and pharmacological screening

1984 ◽  
Vol 49 (4) ◽  
pp. 1002-1008
Author(s):  
Vladimír Valenta ◽  
Antonín Dlabač ◽  
Martin Valchář ◽  
Miroslav Protiva
Keyword(s):  
Thionyl Chloride ◽  
Hydrobromic Acid ◽  
The Other ◽  
Methyl Derivative ◽  
Claisen Reaction ◽  
Pharmacological Screening ◽  
The One ◽  
Related Compounds ◽  
Ethyl Phenylacetate ◽  
Antiarrhythmic Effects

Claisen reaction of 3,4-dimethoxyphenylacetonitrile with ethyl phenylacetate, the following stepwise hydrolysis and decarboxylation afforded the amide V 1-(3,4-dimethoxyphenyl)-3-phenylpropan-2-one (VI). Leuckart reaction resulted in the crude formamide derivative IIIb which was subjected to alkaline hydrolysis to the primary amine Ib on the one hand, and to reduction to the secondary amine IIb on the other. Demethylation with hydrobromic acid gave hydrobromides of 1-(3,4-dihydroxyphenyl)-3-phenyl-2-propylamine (title compound Ia) and its N-methyl derivative IIa. The alcohol VII, obtained by reduction of the ketone VI, was transformed by treatment with thionyl chloride to the chloro compound VIII which afforded by substitution reaction with 1-methylpiperazine the piperazine derivative IX. While the methoxylated amines Ib and IIb have mild stimulating and some antiarrhythmic effects, N-methyl-α-benzyldopamine (IIa) displayed a clear dopaminomimetic character.

1-(3-Dimethylamino-1-phenylpropyl)piperazines and related compounds: Synthesis and pharmacological screening

1981 ◽  
Vol 46 (11) ◽  
pp. 2729-2733 ◽  
Author(s):  
Jiří Jílek ◽  
Josef Pomykáček ◽  
Jiří Němec ◽  
Miroslav Protiva
Keyword(s):  
Short Duration ◽  
Secondary Amine ◽  
Thionyl Chloride ◽  
Local Anaesthetic ◽  
Antiarrhythmic Action ◽  
Substitution Reactions ◽  
Pharmacological Screening ◽  
Hydrolysis Of ◽  
Related Compounds ◽  
Antiarrhythmic Effects

Substitution reactions of N,N-dimethyl-3-chloro-3-phenylpropylamine with 1-methylpiperazine and a series of analogues afforded 1-(3-dimethylamino-1-phenylpropyl)piperazines I-V. A similar substitution with piperidine resulted in the diamine VIII. Hydrolysis of the carbamate V gave the secondary amine VI which was transformed by alkylation with cyclopropylmethyl bromide to compound VII. 3-Dimethylamino-3-phenylpropanol was treated with thionyl chloride to give N,N-dimethyl-3-chloro-3-phenylpropylamine (IX) which reacted with 1-methylpiperazine and afforded the triamine X. The maleates of the amines prepared exhibited hypotensive effects of short duration (III, IV, VI, VII, X) and moderate antiarrhythmic effects (V-VIII). The phenylpiperazine derivative III showed a significant antiarrhythmic action and a high local anaesthetic activity.

N-substituted derivatives of 6,11-dihydrodibenzo[b,e]thiepin-11-amine and related compounds; Synthesis and pharmacological screening

1988 ◽  
Vol 53 (4) ◽  
pp. 860-869 ◽  
Author(s):  
Vladimír Valenta ◽  
Hana Hulinská ◽  
Jiří Holubek ◽  
Antonín Dlabač ◽  
Jan Metyš ◽  
...  
Keyword(s):  
Local Anaesthetic ◽  
Antiarrhythmic Activity ◽  
The Other ◽  
Gastric Ulcers ◽  
Substitution Reactions ◽  
Amino Esters ◽  
Pharmacological Screening ◽  
The One ◽  
Derivatives Of ◽  
Related Compounds

Reactions of N-(6,11-dihydrodibenzo[b,e]thiepin-11-yl)chloroacetamide (II) with dimethylamine, morpholine, and 2-(1-piperazinyl)ethanol afforded the amino amides III-V. Substitution reactions of 11-chloro-6,11-dihydrodibenzo[b,e]thiepin with ethylenediamine and N,N-dimethylethylenediamine gave the diamines VI and VII. 6,11-Dihydrodibenzo[b,e]thiepin-11-amine (I) was treated with ethyl chloroacetate and ethyl 2-bromopropionate to give the amino esters X and XI which were transformed on the one hand to the acids VIII and IX, and to the amides XII and XIII on the other. (6,11-Dihydrodibenzo[b,e]thiepin -11-yl)methylamine (XVIa) and (10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-yl)methylamine (XVIb) were transformed via the chloroacetamides XVIIa and XVIIb to the (4-methyl-1-piperazinyl)acetamides XVa and XVb. Compound V showed local anaesthetic and antiarrhythmic activity, the diamine VII had antihistamine and antireserpine effects, the amide XII was found to be an anticonvulsant, and the piperazines XVa and XVb inhibited effectively the formation of the indomethacin-induced gastric ulcers in rats.

1-[2-(2-Hydroxymethylphenylthio)benzyl]-4-methylpiperzine and related compounds as potential antidepressants: Synthesis and pharmacological acreening

1984 ◽  
Vol 49 (4) ◽  
pp. 1009-1020 ◽  
Author(s):  
Irena Červená ◽  
Miroslav Protiva
Keyword(s):  
Potassium Carbonate ◽  
Secondary Alcohol ◽  
The Other ◽  
Lithium Aluminium Hydride ◽  
Keto Acid ◽  
Open Model ◽  
Lithium Aluminium ◽  
Neuroleptic Agent ◽  
The One ◽  
Related Compounds

Heating of 1-(2-iodobenzoyl)-4-methylpiperazine (II) with thiophenol and its 2-methyl, 4-methyl, 4-chloro and 2-hydroxymethyl derivatives in dimethylformamide in the presence of potassium carbonate, copper and cuprous iodide gave the piperazides IV-VIII; compound VIII was transformed by reduction with lithium aluminium hydride to the title compound I. The acid IX, obtained by a reaction of 5-chloro-2-iodobenzoic acid with 2-methylthiophenol, was reduced to the alcohol X, which was transformed via the chloride XI to 1-[5-chloro-2-(2-methylphenylthio)-benzyl]-4-methylpiperazine (XII), an open model of the neuroleptic agent clorothepin. Heating of 2,5-dichloroacetophenone with thiosalicylic acid afforded the keto acid XIII whose reaction with 1-methylpiperazine was carried out with the help of N,N"-carbonyldiimidazole. The piperazide XIV obtained was reduced on the one hand with sodium borohydride to the secondary alcohol XV, and with lithium aluminium hydride to 1-(2-[4-chloro-2-(1-hydroxyethyl)phenylthio]benzyl)-4-methylpiperazine (XVI) on the other. None of the dibasic piperazines (I, XII, XVI) did show antireserpine activity. In the general screening, some of the piperazides displayed a mild hypotensive (II, VIII, XIV, XV), adrenolytic (VIII), mild stimulating and antitussic (V), and spasmolytic, antiinflammatory and negatively ino- and chronotropic (XIV) activities.

α-(4-Tolyl)dopamine, derivatives and analogues; Synthesis and pharmacological screening

1983 ◽  
Vol 48 (5) ◽  
pp. 1447-1464 ◽  
Author(s):  
Vladimír Valenta ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Antonín Dlabač ◽  
Marie Bartošová ◽  
...  
Keyword(s):  
Acetic Anhydride ◽  
Hydrobromic Acid ◽  
Benzoyl Chloride ◽  
Substitution Reactions ◽  
Low Degree ◽  
Anticataleptic Activity ◽  
Pharmacological Screening ◽  
Higher Doses ◽  
Hydroxyethyl Piperazine ◽  
Antiarrhythmic Effects

The ketone XIII, obtained by Friedel-Crafts reaction of toluene with homoveratroyl chloride, was converted by the Leuckart reaction to the formamido derivative IXb which was used as the starting product for the synthesis of amines IIIb-Vb. Reduction of the ketone XIII gave the alcohol XVI which was treated with hydrogen chloride and afforded the chloro compound XVII. Its substitution reactions with 1-methylpiperazine, 1-(2-hydroxyethyl)piperazine and 1-phenylpiperazine resulted in the piperazines VIb-VIIIb. Acylations of the amine IIIb with acetic anhydride and homoveratroyl chloride gave the amides Xb and XIb which, together with the formamide IXb, were subjected to the Bischler-Napieralski reaction. 3,4-Dihydroisoquinolines XXII-XXIV were obtained and reduced to the 1,2,3,4-tetrahydroisoquinolines XXVb-XXVIIb. Treatment of XXVIIb with formaldehyde afforded the berbine derivative XXVIII. Demethylation of the amine IIIb with hydrobromic acid resulted in the title compound IIIa. Similar demethylations of the dimethoxyamines IVb-VIIIb, XXVb and XXVIb led to the dihydroxyamines IVa-VIIIa, XXVa and XXVIa which are dopamine derivatives. Reaction of Va with benzoyl chloride gave the dibenzoate XXX. The CNS activities of the compounds prepared are of a low degree. Several of them (IIIa-VIa, IIIb-Vb, XXVb) show in higher doses signs of central stimulant action but only for compound IVa an antireserpine effect was proven. The expected anticataleptic activity was found only in a low degree with compound VIIIa; on the contrary, compounds IIIa and XXVa are procataleptogenic. Some compounds (IIIa, IXb, XXVIa, XXVIII) potentiated thiopental. In single cases local anaesthetic, spasmolytic, hypotensive, hypertensive, hypoglycaemic, diuretic and antiarrhythmic effects were observed.

Potential nootropic agents: Synthesis of some (2-oxo-1-pyrrolidinyl)acetamides and some related compounds

1990 ◽  
Vol 55 (11) ◽  
pp. 2756-2764 ◽  
Author(s):  
Vladimír Valenta ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Martin Valchář ◽  
Ivan Krejčí ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Survival Time ◽  
Acetyl Chloride ◽  
The Other ◽  
Anticonvulsant Effect ◽  
Mixed Anhydride ◽  
Ester Exchange ◽  
Nootropic Agents ◽  
The One ◽  
Related Compounds

Ethyl (2-oxo-1-pyrrolidinyl)acetate was transformed by ester exchange to the 2-dimethylaminoethyl ester VI which was converted to the choline iodide ester VII. The mixed anhydride of (2-oxo-1-pyrrolidinyl)acetic acid and monoethyl carbonate was reacted with ethyl aminoacetate to give the ester VIII which was transformed on the one hand to the amide IX, and to the 2-dimethylaminoethyl ester X on the other. Reaction of the latter with methyl iodide afforded a further choline iodide ester XI. Reactions of (2-oxo-1-pyrrolidinyl)acetyl chloride with 4-chloroaniline and 3-aminopyridine gave the amides XII and XIV. The anilide XIII was obtained from 2-(2-oxo-1-pyrrolidinyl)butyric acid and 4-chloroaniline by means of dicyclohexylcarbodiimide. The benzo analogue (XV) of piracetam (I) was synthesized from oxindole via the ester XVI. The anilide XII (V⁄FB-16 536) was found to potentiate significantly the anticonvulsant effect of diazepam in mice, to prolong the survival time of mice under conditions of nitrogen anoxia, and to prolong significantly the duration of the "gasping reflex" in mice.

GUANIDINE: A SIMPLE MOLECULE WITH GREAT POTENTIAL: FROM CATALYSTS TO BIOCIDES AND MOLECULAR GLUES

INEOS OPEN ◽  
2021 ◽  
Author(s):  
F. V. Drozdov ◽  
◽  
V. M. Kotov ◽  
Keyword(s):  
Smart Materials ◽  
Crucial Role ◽  
Chemical Properties ◽  
Structural Features ◽  
The Other ◽  
Synthetic Drugs ◽  
Guanidine Derivatives ◽  
Living Organisms ◽  
The One ◽  
Related Compounds

This review is devoted to the general methods for obtaining guanidine derivatives and related compounds, their chemical properties, and structural features. On the one hand, guanidine and its derivatives play a crucial role in the metabolism of living organisms. On the other hand, owing to their unique properties and simple synthesis, the guanidine derivatives are used as synthetic drugs and biocidal agents, catalysts, ligands, and sweeteners. Furthermore, the guanidine derivatives serve as a basis for the creation of modern smart materials.

Note on Selection of Coordinate Systems for Geodynamics

1975 ◽  
Vol 26 ◽  
pp. 395-407
Author(s):  
S. Henriksen
Keyword(s):  
Sea Level ◽  
The Other ◽  
Coordinate Systems ◽  
Mean Sea Level ◽  
The Earth ◽  
The One ◽  
Static Systems ◽  
Selection Of

The first question to be answered, in seeking coordinate systems for geodynamics, is: what is geodynamics? The answer is, of course, that geodynamics is that part of geophysics which is concerned with movements of the Earth, as opposed to geostatics which is the physics of the stationary Earth. But as far as we know, there is no stationary Earth – epur sic monere. So geodynamics is actually coextensive with geophysics, and coordinate systems suitable for the one should be suitable for the other. At the present time, there are not many coordinate systems, if any, that can be identified with a static Earth. Certainly the only coordinate of aeronomic (atmospheric) interest is the height, and this is usually either as geodynamic height or as pressure. In oceanology, the most important coordinate is depth, and this, like heights in the atmosphere, is expressed as metric depth from mean sea level, as geodynamic depth, or as pressure. Only for the earth do we find “static” systems in use, ana even here there is real question as to whether the systems are dynamic or static. So it would seem that our answer to the question, of what kind, of coordinate systems are we seeking, must be that we are looking for the same systems as are used in geophysics, and these systems are dynamic in nature already – that is, their definition involvestime.

Stories and the Self

2020 ◽  
Vol 32 (2) ◽  
pp. 47-58 ◽  
Author(s):  
Stefan Krause ◽  
Markus Appel
Keyword(s):  
Meta Analysis ◽  
The Self ◽  
The Other ◽  
Lower Degree ◽  
Contrast Effects ◽  
Self Perception ◽  
Self Perceptions ◽  
Other Hand ◽  
The One ◽  
Implicit And Explicit

Abstract. Two experiments examined the influence of stories on recipients’ self-perceptions. Extending prior theory and research, our focus was on assimilation effects (i.e., changes in self-perception in line with a protagonist’s traits) as well as on contrast effects (i.e., changes in self-perception in contrast to a protagonist’s traits). In Experiment 1 ( N = 113), implicit and explicit conscientiousness were assessed after participants read a story about either a diligent or a negligent student. Moderation analyses showed that highly transported participants and participants with lower counterarguing scores assimilate the depicted traits of a story protagonist, as indicated by explicit, self-reported conscientiousness ratings. Participants, who were more critical toward a story (i.e., higher counterarguing) and with a lower degree of transportation, showed contrast effects. In Experiment 2 ( N = 103), we manipulated transportation and counterarguing, but we could not identify an effect on participants’ self-ascribed level of conscientiousness. A mini meta-analysis across both experiments revealed significant positive overall associations between transportation and counterarguing on the one hand and story-consistent self-reported conscientiousness on the other hand.

Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome

2005 ◽  
Vol 44 (03) ◽  
pp. 107-117
Author(s):  
R. G. Meyer ◽  
W. Herr ◽  
A. Helisch ◽  
P. Bartenstein ◽  
I. Buchmann
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Primary Tumour ◽  
The Other ◽  
Haematopoietic Stem Cell ◽  
Other Hand ◽  
Primary Reduction ◽  
The One ◽  
Acute Myeloid

SummaryThe prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term diseasefree survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myeloablative conditioning before SCT.This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand.

Das Ende der Postdemokratie, den Pessimismus überwinden.

2017 ◽  
Vol 47 (188) ◽  
pp. 487-494
Author(s):  
Daniel Mullis
Keyword(s):  
Political Thought ◽  
Social Dynamics ◽  
Social Conditions ◽  
The Other ◽  
Economic Decline ◽  
Far Right ◽  
Windows Of Opportunity ◽  
Political Events ◽  
Political Struggles ◽  
The One

In recent years, political and social conditions have changed dramatically. Many analyses help to capture these dynamics. However, they produce political pessimism: on the one hand there is the image of regression and on the other, a direct link is made between socio-economic decline and the rise of the far-right. To counter these aspects, this article argues that current political events are to be understood less as ‘regression’ but rather as a moment of movement and the return of deep political struggles. Referring to Jacques Ranciere’s political thought, the current conditions can be captured as the ‘end of post-democracy’. This approach changes the perspective on current social dynamics in a productive way. It allows for an emphasis on movement and the recognition of the windows of opportunity for emancipatory struggles.

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