1-(4-Cyclopentylphenyl)ethylamine and derivatives: Synthesis and pharmacological screening

Reduction of 4-cyclopentylacetophenone oxime gave the title compound II which was transformed by a combination of acylation, alkylation, reduction and substitution reactions to compounds III-XI. 2-Benzylcyclopentanone oxime was reduced to 2-benzylcyclopentylamine (XVI) and converted by a reaction with methylmagnesium iodide and by the following Ritter reaction to the formamide derivative XVIII which was used as the starting material for preparing amines XIX-XXI. The local anaesthetic and spasmolytic activity were the most typical neurotropic effects of derivatives of compound II. 2-Benzyl-1-methylcyclopentylamine and derivatives XIX-XXI have some hypotensive activity.

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

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19880860 ◽

1988 ◽

Vol 53 (4) ◽

pp. 860-869 ◽

Cited By ~ 3

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.

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6,11-Dihydrodibenzo[b,e]thiepin-11-thiol and 11-acetic acid derivatives; Some 2-methyl-6,11-dihydrodibenzo[b,e]thiepins; Synthesis and pharmacological screening

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19792689 ◽

1979 ◽

Vol 44 (9) ◽

pp. 2689-2701 ◽

Cited By ~ 1

Author(s):

Vladimír Valenta ◽

František Kvis ◽

Jiří Němec ◽

Miroslav Protiva

Keyword(s):

Acetic Acid ◽

Zinc Chloride ◽

Local Anaesthetic ◽

Diethyl Malonate ◽

Acetyl Derivative ◽

Cardiovascular Activity ◽

Starting Compound ◽

Pharmacological Screening ◽

Neurotropic Effects ◽

Sodium Amide

11-Chloro-6,11-dihydrodibenzo[b,e]thiepin was transformed via the isothiourea V to the thiol IV which was used for the synthesis of aminoalkyl sulfides VII and VIII and of the methylpiperazide X. The same starting compound was used for alkylating diethyl malonate and via the intermediates XIV and XV, 6,11-dihydrodibenzo[b,e]thiepin-11-acetic acid (XVI) was obtained, which was converted to the methylpiperazide XVIII. Oxime XIX and 2-diethylaminoethylimine XX were prepared from 2-methyldibenzo[b,e]thiepin-11(6H)-one (II). Reduction of the ketone II afforded 2-methyl-6,11-dihydrodibenzo[b,e]thiepin (XII) giving by treatment with sodium amide and 3-dimethylaminopropyl chloride the amine XXIII. In the reaction of 6,11-dihydrodibenzo[b,e]thiepin-11-ol with sodium amide and 3-dimethylaminopropyl chloride, C-alkylation took place in addition to the expected etherification resulting in the diamine XXII. Reaction of phthalide with 4-aminothiophenol gave the acid XXIV which was transformed to the 3-dimethylaminopropyl ester XXV and N-acetyl derivative XXVI. Compound XXVI was cyclized with zinc chloride to the ketone III. Some of the compounds prepared exhibit structurally less specific peripheral and vegetative neurotropic effects (local anaesthetic, spasmolytic) and cardiovascular activity (antiarrhytmic).

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

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19812729 ◽

1981 ◽

Vol 46 (11) ◽

pp. 2729-2733 ◽

Cited By ~ 1

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.

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N-(Aminoacyl) and N-(aminoalkyl) derivatives of 4-cyclopentylaniline and N-ethyl-4-cyclopentylaniline; Synthesis and pharmacological screening

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19830156 ◽

1983 ◽

Vol 48 (1) ◽

pp. 156-162 ◽

Cited By ~ 2

Author(s):

Zdeněk Vejdělek ◽

Marie Bartošová ◽

Miroslav Protiva

Keyword(s):

Lithium Aluminium Hydride ◽

Substitution Reactions ◽

Rotarod Test ◽

Lithium Aluminium ◽

Local Anaesthetic Effect ◽

Anorectic Effect ◽

Pharmacological Screening ◽

Derivatives Of ◽

Higher Doses ◽

Anaesthetic Effect

Acylation of 4-cyclopentylaniline (I) with chloracetyl chloride, 3-chloropropionyl chloride, 4-chlorobutyryl chloride and 2-bromo-4-methylvaleryl bromide gave the halogenoacyl derivatives IV - VII out of which the first two were subjected to substitution reactions with diethylamine and piperidine. The N-(aminoacyl) derivatives VIII - XI obtained were reduced with lithium aluminium hydride to the N-(aminoalkyl) derivatives XII and XV. N-Ethyl-4-cyclopentylaniline (XVI), prepared by reduction of N-(4-cyclopentylphenyl)acetamide (II), was similarly transformed via the chloroacetyl derivative XVII to the amide XVIII and the diamine XIX. Salts of the compounds prepared (amino amides and diamines) bring about in higher doses central excitation which is apparently in close connection with the found discoordinating effect of a part of products (VIII - XI, XIII) in the rotarod test, further with the antireserpine effects in the tests of antagonization of reserpine ptosis and hypothermia (VIII, X, XII, XIII) and finally with the anorectic effect of compound X. All substances showed a mild spasmolytic effect of the anticholinergic type. On the other hand, the expected local anaesthetic effect was found only with compounds VIII, XVIII, XIX.

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The 3-Deaza and 7-Deaza Derivatives of 5'-Amino-5'-deoxy-5'-noraristeromycin

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20061122 ◽

2006 ◽

Vol 71 (7) ◽

pp. 1122-1129 ◽

Cited By ~ 1

Author(s):

Minmin Yang ◽

Tesfaye Serbessa ◽

Stewart W. Schneller

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Starting Material ◽

Allylic Substitution ◽

Weak Effect ◽

Substitution Reactions ◽

Standard Procedures ◽

B Virus ◽

The Common ◽

Derivatives Of

The 3-deaza and 7-deaza derivatives of 5'-amino-5'-deoxy-5'-noraristeromycin (6 and 7, respectively) have been prepared from the common starting material (+)-(1R,4S)-4-hydroxycyclopent-2-en-1-yl acetate (8). Two Pd(0)-catalyzed allylic substitution reactions afforded the desired azide intermediates, 12 and 16, which were transformed to target compounds by standard procedures. These compounds were evaluated against a large number of viruses and found to be inactive except for weak effect against hepatitis B virus: 6, EC50 4.7 μM (3TC EC50 0.056 μM); 7, EC50 4.8 μM (3TC EC50 0.063 μM).

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Potential anticonvulsants: Substituted N-benzylidene derivatives of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19831173 ◽

1983 ◽

Vol 48 (4) ◽

pp. 1173-1186 ◽

Cited By ~ 2

Author(s):

Václav Bártl ◽

Jiří Holubek ◽

Emil Svátek ◽

Marie Bartošová ◽

Miroslav Protiva

Keyword(s):

Acute Toxicity ◽

Water Soluble ◽

Hypotensive Activity ◽

Anticonvulsant Effect ◽

Maximal Electroshock ◽

Soluble Salts ◽

Sleeping Time ◽

Central Depression ◽

Derivatives Of ◽

Electroshock Seizures

Reactions of 10-(4-aminopiperazino)-10,11-dihydrodibenzo[b,f]thiepins XIVa-XIVd with benzaldehyde, 3,4-dimethoxybenzaldehyde, 4-dimethylaminobenzaldehyde, salicylaldehyde, 3-ethoxy-4-hydroxybenzaldehyde, 2-(2-dimethylaminoethoxy)benzaldehyde, 3-(2-dimethylaminoethoxy)benzaldehyde and 3-ethoxy-4-(2-dimethylaminoethoxy)benzaldehyde afforded a series of 19 hydrazones IIIa-Xc. Some of them showed the expected anticonvulsant effect but only towards pentetrazole; antagonism of maximal electroshock seizures was not observed. In general, the products have a character of tranquillizers: in higher does they produce central depression, potentiate the thiopental sleeping time, have hypothermic action; in single cases antiamphetamine, antireserpine, antihistamine and cataleptic effects were observed. The water-soluble salts of the basic hydrazones VIIIa, VIIIc, IXc and Xc, administered parenterally, showed a rather high acute toxicity and revealed also adrenolytic and hypotensive activity.

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Fluorinated tricyclic neuroleptics with prolonged action: 8-Methoxy, 8-ethoxy, 8-ethylthio and 8-hydroxy derivatives of 3-fluoro-10-(4-methylpiperazino)-10,11-dihydrodibenzo[b,f]thiepin

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19821382 ◽

1982 ◽

Vol 47 (5) ◽

pp. 1382-1391 ◽

Cited By ~ 2

Author(s):

Jiří Jílek ◽

Josef Pomykáček ◽

Jiřina Metyšová ◽

Miroslav Protiva

Keyword(s):

Acetic Acid ◽

Polyphosphoric Acid ◽

Prolonged Action ◽

Substitution Reactions ◽

Methoxy Derivative ◽

Chloro Derivatives ◽

Boron Tribromide ◽

Derivatives Of ◽

Central Depressant ◽

Boiling Toluene

Acids IIa-c were prepared by reactions of (4-fluoro-2-iodophenyl)acetic acid with 4-methoxythiophenol, 4-ethoxythiophenol and 4-(ethylthio)thiophenol and cyclized with polyphosphoric acid in boiling toluene to dibenzo[b,f]thiepin-10(11H)-ones IIIa-c. Reduction with sodium borohydride afforded the alcohols IVa-c which were treated with hydrogen chloride and gave the chloro derivatives Va-c. Substitution reactions with 1-methylpiperazine resulted in the title compounds Ia-c out of which the methoxy derivative Ia was transformed by demethylation with boron tribromide to the phenol Id. Compounds Ia-d are very potent neuroleptics exhibiting a clear prolongation of the central depressant and some prolongation of the cataleptic activity.

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3-(s-Hydrindacen-4-yl)propylamines and 4-(s-hydrindacen-4-yl)butylamines; Synthesis and pharmacological screening

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19811800 ◽

1981 ◽

Vol 46 (8) ◽

pp. 1800-1807 ◽

Cited By ~ 1

Author(s):

Zdeněk Vejdělek ◽

Marie Bartošová ◽

Miroslav Protiva

Keyword(s):

Malonic Acid ◽

Local Anaesthetics ◽

Lithium Aluminium Hydride ◽

Spasmolytic Activity ◽

Lithium Aluminium ◽

Malonic Acid Derivatives ◽

Pharmacological Screening ◽

Hydroxyethyl Piperazine

4-Chloromethyl-s-hydrindacene (VIIa) was transformed via the malonic acid derivatives VIIIa and IXa to the acid Xb which afforded in four steps the homological acid Xc. Reactions of chlorides of both acids (XIbc ) with dimethylamine, 1-methylpiperazine and 1-(2-hydroxyethyl)piperazine led to the amides XIIbc-XIVbc which were reduced with lithium aluminium hydride to the title compounds IVcd-VIcd. The amines obtained show central neuroleptic effects only in subtoxic doses; they are also potent local anaesthetics and have significant spasmolytic activity of the neurotropic as well as musculotropic type.

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