Potential hypnotics and anxiolytics: Synthesis of 2-bromo-4-(2-chlorophenyl)-9-[4-(2-methoxyethyl)piperazino]-6H-thieno[3,2,4-triazolo[4,3-a]-1,4-diazepine and of some related compounds

1984 ◽  
Vol 49 (3) ◽  
pp. 621-636 ◽  
Author(s):  
Zdeněk Polívka ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Jan Metyš ◽  
Miroslav Protiva
Keyword(s):  
Title Compound ◽  
Point Of View ◽  
Triethyl Orthoformate ◽  
Substitution Reactions ◽  
Bromo Derivative ◽  
Anticonvulsant Activities ◽  
Related Compounds

The synthesis of 2,9-dibromo-4-(2-chlorophenyl)-6H-thieno[3,2-f]-1,2,4-triazolo[4,3-a]-1,4,diazepine (XX) has been carried out. The substitution reactions of XX with 1-(2-methoxyethyl) piperazine, 1-(3-methoxypropyl)piperazine, 1-(2-ethoxyethyl)piperazine and 1-(2-methylthiothyl)-piperazine afforded the title compound XXIV and its analogues XXV-XXVII. N-Alkylations of 2-bromo-4-(2-chlorophenyl)-9-piperazino-6H-thieno[3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine (XXIII) with 2-phenoxyethyl bromide and 2-phenylthioethyl bromide gave compounds XXVIII and XXIX. Cyclization of 5-(2-chlorophenyl)-2-hydrazino-3H-thieno[2,3-e]-1,4-diazepine(XVIIIa) by treatment with triethyl orthoformate resulted in 4-(2-chlorophenyl)-6H-thieno[3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine (XIX) which could be brominated only to the 9-bromo derivative XXI; attempts at further bromination to position 2 were unsuccessful. Some contribution to the syntheses of etizolam (I) and its dechloro analogue V in the stage of intermediates are being described. Compounds XXIV-XXIX were pharmacologically tested from the point of view of discoordinating and anticonvulsant activities; they proved less active than the analogous 8-chloro-6-(2-chlorophenyl)-1-piperazino-4H-striazolo[4,3-a]-1,4-benzodiazepines.

Potential hypnotics and anxiolytics in the 4H-s-triazolo[4,3-a]-1,4-benzodiazepine series: 8-Chloro-6-(2-chlorophenyl)-1-[4-(2-methoxyethyl)piperazino]-4H-s-triazolo[4,3-a]-1,4-benzodiazepine and some related compounds

1983 ◽  
Vol 48 (8) ◽  
pp. 2395-2410 ◽  
Author(s):  
Zdeněk Polívka ◽  
Miroslav Ryska ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Jan Metyš ◽  
...  
Keyword(s):  
Title Compound ◽  
Substitution Reaction ◽  
Gradual Decrease ◽  
Substitution Reactions ◽  
Bromo Derivative ◽  
Related Compounds ◽  
Very High

1-Bromo derivatives XIIa and XIIb were prepared by bromination of 8-chloro-6-phenyl-4H-s-triazolo[4,3-a]-1,4-benzodiazepine (XIa) and its 6-(2-chlorophenyl) analogue XIb with bromine in chloroform in the presence of pyridine. Substitution reactions with 1-(2-methoxyethyl)piperazine (XIVb), 1-(3-methoxypropyl)piperazine (XVb), 1-(2-ethoxyethyl)piperazine (XVIb) and 1-(2-methylthioethyl)piperazine (XVIIb) afforded the title compound IIb and analogues IIa and IIIb-Vb. A substitution reaction of the bromo derivative XIIb with piperazine gave the 1-piperazino derivative VIIIb which was alkylated with 2-phenoxyethyl bromide and 2-phenylthioethyl bromide to give compounds VIb and VIIb. The title compound IIb has very high anticonvulsant and discoordinating activities in mice. The enlargement of the substituent R1 (compounds IIIb-VIIb) results in a gradual decrease of the effects mentioned.

Neuroleptic agents derived from perathiepin: 6,7-Dichloro derivative of 10-(4-methylpiperazino)-10,11-dihydrodibenzo[b,f]thiepin and related compounds

1981 ◽  
Vol 46 (7) ◽  
pp. 1607-1613 ◽  
Author(s):  
Jiří Jílek ◽  
Josef Pomykáček ◽  
Jiřina Metyšová ◽  
Miroslav Protiva
Keyword(s):  
Benzoic Acid ◽  
Title Compound ◽  
Titanium Tetrachloride ◽  
Substitution Reactions ◽  
Related Compounds ◽  
Hydroxyethyl Piperazine ◽  
Central Depressant ◽  
Dichloro Derivative ◽  
Iodobenzoic Acid

The reaction of 2,3-dichlorothiophenol with 2-iodobenzoic acid gave 2-(2,3-dichlorophenylthio)benzoic acid (V) which was transformed in four steps to the homological acid IX. Cyclization resulted in 6,7-dichlorodibenzo[b,f]thiepin-10(11H)-one (X) which was converted via the alcohol XI to the trichloro compound XII. Substitution reactions of XII with 1-methylpiperazine and 1-(2-hydroxyethyl)piperazine afforded the title compound I and its hydroxyethyl analogue II. Reaction of the ketone X with 1-methylpiperazine and titanium tetrachloride gave the enamine III. Compounds I-III exhibit mild central depressant and relatively strong cataleptic activity.

Noncataleptic neuroleptic agents: 2-(4-(2-(2-Chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yloxy)ethyl)piperazine-1-yl)ethanol and some related compounds

1988 ◽  
Vol 53 (11) ◽  
pp. 2731-2741 ◽  
Author(s):  
Jiří Jílek ◽  
Martin Valchář ◽  
Jiří Holubek ◽  
Nataša Dlohožková ◽  
Josef Pomykáček ◽  
...  
Keyword(s):  
Preclinical Studies ◽  
Acid Chlorides ◽  
Substitution Reactions ◽  
Related Compounds

10-(2-Bromoethoxy)-2-chloro-10,11-dihydrodibenzo[b,f]thiepin (X), prepared by two methods, was subjected to substitution reactions with 2-(1-piperazinyl)ethanol, 3-(1-piperazinyl)propanol, 1-methylpiperazine, 3-(1-piperazinyl)propionamide, piperazine, and 1-(ethoxycarbonyl)piperazine and gave the title compounds II-VII. The alcohol II was esterified by treatment with acid chlorides to compounds VIII and IX. Compounds II, V, and VIII proved to be noncataleptic neuroleptic agents and II (clopithepin, VÚFB-17 076) was selected for preclinical studies.

Antiaminic agents derived from thieno[2,3-c]-2-benzothiepin: 4-(1-Methyl-4-piperidylidene)-4,9-dihydrothieno[2,3-c]-2-benzothiepin and some related compounds

1983 ◽  
Vol 48 (2) ◽  
pp. 623-641 ◽  
Author(s):  
Zdeněk Polívka ◽  
Miroslav Rajšner ◽  
Jan Metyš ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Sulfuric Acid ◽  
Title Compound ◽  
Amino Alcohol ◽  
Hydrogen Sulfate ◽  
Geometric Isomers ◽  
Pure Alcohol ◽  
Acid Catalyzed ◽  
Anticataleptic Activity ◽  
Related Compounds

In the reaction of thieno[2,3c]-2-benzothiepin-4(9H)-one (VI) with 1-methyl-4-piperidylmagnesium chloride 7-(1-methyl-4-piperidyl)thieno[2,3-c]-2-benzothiepin-4(9H)-one (VIII) is formed in addition to the expected amino alcohol VII. The title compound I was obtained by the acid catalyzed dehydration of the pure alcohol VII. Compound I (pipethiadene) has outstanding antihistamine, antiserotonin, antireserpine and anticataleptic activity and was recommended to clinical trials as a potential antimigraine agent. For pharmacokinetic and metabolic studies there were prepared the NC2H3 analogue of pipethiadene IV and further, as potential metabolites, the demethyl analogue III, S-oxide X, demethyl S-oxide XI, N-oxide XIII and N,S-dioxide XIV. The Witting reaction of the ketone VI with 3-dimethylaminopropylidenetriphenylphosphorane resulted in a mixture of geometric isomers of 4-(3-dimethylamino-propylidene)-4,9-dihydrothieno[2,3-c]-2-benzothiepin with the strongly predominating Z-isomer XVI which was isolated from the mixture by crystallization of the hydrogen maleate. The mixture with the predominating Z-isomer XVI was converted by the treatment with 80% sulfuric acid and dilution with water to a mixture with the predominating E-isomer XV (dithiadene) which was isolated by crystallization of the hydrogen sulfate. Some further new thieno[2,3-c]-2-benzothiepin derivatives were synthesized as potential intermediates.

Experimental evidence for the amino-group non-planarity in nitroanilines: neutron diffraction study of 2-methyl-5-nitroaniline at 100 K

1999 ◽  
Vol 55 (2) ◽  
pp. 209-215 ◽  
Author(s):  
Javier Ellena ◽  
Andrés E. Goeta ◽  
Judith A. K. Howard ◽  
Chick C. Wilson ◽  
Juan C. Autino ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Neutron Diffraction ◽  
Experimental Evidence ◽  
Diffraction Study ◽  
Title Compound ◽  
Neutron Diffraction Study ◽  
Amino Group ◽  
X Ray ◽  
Related Compounds ◽  
Centrosymmetric Dimers

An appreciable degree of pyramidalization of the amine N atom is observed in the title compound. The existence of polar chains, induced by N—H...O synthons, is confirmed. C—H...O interactions, not noted in a previous X-ray study, were found to stabilize further the known head-to-tail assembling of the chains. The structure can be described as non-polar (101) layers, embodying chains interlinked by centrosymmetric dimers, connected by C(aryl)—H...π interactions. The latter are not present in m-nitroaniline, 2-methyl-4-nitroaniline and other related compounds with chains built from similar N—H...O synthons and assembled head-to-head. This finding implies that an obvious relationship between molecular recognition patterns and crystal structures should not be assumed.

Synthesis of 14-hydroxy steroids. Total synthesis of methyl 14β-hydroxy-1,7,17-trioxo-5β,8-androstene-10β-oate and related compounds

1990 ◽  
Vol 68 (11) ◽  
pp. 1917-1922 ◽  
Author(s):  
Réjean Ruel ◽  
Pierre Deslongchamps
Keyword(s):  
Total Synthesis ◽  
Ammonium Salt ◽  
Michael Addition ◽  
Title Compound ◽  
Steroid Synthesis ◽  
Related Compounds ◽  
Acetylenic Ketone

The total synthesis of the title compound 22 and methyl 14α-hydroxy-5β,13α,8-androstene-1,7,17-trioxo-10β-oate 21 isomer is reported. We also describe the 1,6-Michael addition of 2-methyl-1,3-cyclopentanedione on dienone 14 and the protic ammonium salt catalyzed intramolecular Michael addition of cyclic β-ketoester on the conjugated acetylenic ketone 13. Keywords: cardenolides, steroid synthesis, aldol, Michael addition.

scholarly journals Crystal structure ofO-ethylN-(ethoxycarbonyl)thiocarbamate

2015 ◽  
Vol 71 (10) ◽  
pp. o782-o783 ◽  
Author(s):  
Matthew J. Henley ◽  
Alex M. Schrader ◽  
Victor G. Young ◽  
George Barany
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Least Squares ◽  
Title Compound ◽  
Compound C ◽  
The One ◽  
Related Compounds ◽  
Centrosymmetric Dimers

The title compound, C6H11NO3S, provides entries to novel carbamoyl disulfanes and related compounds of interest to our laboratory. The atoms of the central O(C=S)N(C=O)O fragment have an r.m.s. deviation of 0.1077 Å from the respective least-squares plane. While several conformational orientations are conceivable, the crystal structure shows only the one in which the carbonyl and the thiocarbonyl moieties areantito each other across the central conjugated C—N—C moiety. Pairs of 2.54 Å N—H...S=C hydrogen bonds between adjacent molecules form centrosymmetric dimers in the crystal.

Potential antidepressants. Synthesis of 6,11-dihydrodibenzo[b,e]thiepin-11-yl (dimethylaminomethyl)phenyl ethers, sulfides, amines and some related compounds

1990 ◽  
Vol 55 (1) ◽  
pp. 282-295 ◽  
Author(s):  
Karel Šindelář ◽  
Vladimír Valenta ◽  
Jiří Holubek ◽  
Oluše Matoušová ◽  
Miroslav Protiva
Keyword(s):  
Sodium Carbonate ◽  
Antidepressant Agents ◽  
Antimicrobial Effects ◽  
Bromo Derivative ◽  
Methyl Derivatives ◽  
Phenyl Ethers ◽  
Related Compounds

Reactions of 11-chloro-6,11-dihydrodibenzo[b,e]thiepin and its 2-bromo derivative with the isomeric (dimethylaminomethyl)phenols, (dimethylaminomethyl)thiophenols, and (dimethylaminomethyl)anilines in toluene afforded the title compounds IIIb,c, Va, VIIIa,b,c, and Xa,b,c. Reactions of 11-chloro-6,11-dihydrodibenzo[b,e]thiepin and its 2-chloro and 2-methyl derivatives with N,N-dimethyl-2-(4-aminophenoxy)ethylamine and N,N-dimethyl-3-(4-aminophenoxy)propylamine by heating in dimethylformamide in the presence of sodium carbonate gave the diamino ethers XI-XIV. The compounds showed only indications of the antidepressant agents profile and some antimicrobial effects in vitro.

Conformational analysis of the products of 1,4 addition of Tri(phenylthio)methyllithium to α,β-unsaturated ketones. The X-ray structuredetermination of 4-Phenyl-5,5,5-tri(phenylthio)pentan-2-one

1981 ◽  
Vol 34 (12) ◽  
pp. 2671
Author(s):  
AB Manas ◽  
RAJ Smith ◽  
J Simpson
Keyword(s):  
Conformational Analysis ◽  
Dihedral Angle ◽  
Spin System ◽  
Title Compound ◽  
Second Order ◽  
Coupling Constants ◽  
X Ray ◽  
Unsaturated Ketones ◽  
Iterative Analysis ◽  
Related Compounds

Iterative analysis of the second-order ABX spin system in the 1H n.m.r. of the title compound gave coupling constants which are consistent with a conformation involving a H-C-C-H dihedral angle of about 90�. The structure was confirmed by X-ray analysis. The 1H n.m.r. of the related compounds 2,2-dimethyl-5-pheny1-6,6,6-tri(phenylthio)hexan-3-one and 1,3-diphenyl-4,4,4-tri(pheny1-thio)butan-1-one were also analysed and found to have similar conformational characteristics.

6a-Thiathiophthens and related compounds. Part II. Substitution reactions

1971 ◽  
pp. 963 ◽  
Author(s):  
R. J. S. Beer ◽  
D. Cartwright ◽  
R. J. Gait ◽  
D. Harris
Keyword(s):  
Substitution Reactions ◽  
Related Compounds
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