Basic amides of 2,4,5-trichlorophenoxyacetic, 2,4,6-trimethylphenoxyacetic and 4-bromo-3,5-dimethylphenoxyacetic acid and some related compounds; Synthesis and pharmacological screening

1983 ◽  
Vol 48 (4) ◽  
pp. 1089-1096 ◽  
Author(s):  
Vladimír Valenta ◽  
Jiří Němec ◽  
Miroslav Protiva
Keyword(s):  
Local Anaesthetic ◽  
Methyl Esters ◽  
Acid Chlorides ◽  
Basic Amides ◽  
Pharmacological Screening ◽  
Cns Effects ◽  
Related Compounds ◽  
Hydroxyethyl Piperazine

Reactions of methyl esters II of 2,4,5-trichlorophenoxyacetic (Ia), 2,4,6-trimethylphenoxyacetic (Ib) and 4-bromo-3,5-dimethylphenoxyacetic acid (Ic) with 2-diethylaminoethylamine, 2-morpholinoethylamine, 3-morpholinopropylamine, 1-methylpiperazine, 3-(4-methylpiperazino)propylamine, 3-[4-(2-tolyl)piperazino]propylamine and 1,4-bis(3-aminopropyl)piperazine in boiling ethanol gave the basic amides Va-XIc which were isolated as hydrochlorides. Reactions of the acid chlorides IVa and IVb with 1,4-bis(2-hydroxyethyl)piperazine and 1,4-bis(3-hydroxypropyl)piperazine in dimethylformamide resulted directly in dihydrochlorides of diesters XIIab and XIIIab. The compounds prepared have only weak CNS effects (mostly of the depressant type); they have local anaesthetic, mild hypotensive (some of them adrenolytic), antiarrhythmic and peripheral vasodilating activities.

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.

4-(Aminoacylamido)-s-hydrindacenes and related compounds: Synthesis and pharmacological screening

1982 ◽  
Vol 47 (12) ◽  
pp. 3297-3305 ◽  
Author(s):  
Zdeněk Vejdělek ◽  
Jiří Holubek ◽  
Marie Bartošová ◽  
Miroslav Protiva
Keyword(s):  
Methyl Iodide ◽  
Alkaline Hydrolysis ◽  
Local Anaesthetic ◽  
Antiarrhythmic Activity ◽  
Chloroacetyl Chloride ◽  
Benzoyl Isothiocyanate ◽  
Pharmacological Screening ◽  
High Degree ◽  
Related Compounds ◽  
Imidazoline Derivative

Chloracylamido derivatives IIIa-Va were obtained by acylation of 4-amino-s-hydrindacene with chloroacetyl chloride, 2-chloropropionyl chloride and 3-chloropropionyl chloride; their reactions with excessive diethylamine, pyrrolidine, piperidine and morpholine afforded the title compounds IIIbcde-Vbcde. A reaction of 4-amino-s-hydrindacene with benzoyl isothiocyanate gave 1-benzoyl-3-(s-hydrindacen-4-yl)thiourea (VI) whose mild alkaline hydrolysis resulted in N-(s-hydrindacen-4-yl)thiourea (VII). The following treatment with methyl iodide and then with ethylenediamine afforded the imidazoline derivative VIII in a low yield. N-(s-Hydrindacen-4-yl)-2-piperidinoacetamide (IIId) in the form of the hydrochloride revealed a high degree of local anaesthetic and antiarrhythmic activity.

N-(piperazinoacyl) and N-(piperazinoalkyl) derivatives of 4-cyclopentylaniline and related compounds: Synthesis and pharmacological screening

1986 ◽  
Vol 51 (7) ◽  
pp. 1494-1502
Author(s):  
Zdeněk Vejdělek ◽  
Miroslav Protiva
Keyword(s):  
Similar Reaction ◽  
Lithium Aluminium Hydride ◽  
Antispasmodic Activity ◽  
Analgesic Effects ◽  
Basic Amides ◽  
Lithium Aluminium ◽  
Propionyl Chloride ◽  
Pharmacological Screening ◽  
Derivatives Of ◽  
Related Compounds

Five N-(4-cyclopentylphenyl)haloalkanecarboxamides were reacted with 1-methylpiperazine and 1-(2-hydroxyethyl)piperazine to give the corresponding N-(4-cyclopentylphenyl)piperazinoalkanecarboxamides Iab -Vab. Their reduction with lithium aluminium hydride afforded the triamines VIIab - XIab. Acylation of the N-(4-methylpiperazino)alkyl-4-cyclopentylanilines Xa and XIa with propionyl chloride resulted in the propionanilides XIVa and XVa, whereas a similar reaction of the N-(4-(2-hydroxyethyl)piperazino)alkyl-4-cyclopentylanilines VIIb and IXb - XIb produced the propionoxypropionanilides XIIc - XVc. Ethanolysis of these compounds afforded corresponding hydroxypropionanilides XIIb - XVb. Many of the basic amides showed local anaesthetic and papaverine-like antispasmodic activity. The propionanilides XIIb, XIVc, and XVa proved interesting analgesic effects in the peritoneal test in mice.

11-(3-[4-(2-Hydroxyethyl)piperazino]propylidene)-6,11-dihydrodibenzo[b,e]thiepin, its 2-chloro derivative and some related compounds as potential antipsychotic agents; Synthesis and pharmacology

1984 ◽  
Vol 49 (8) ◽  
pp. 1816-1826 ◽  
Author(s):  
Václav Bártl ◽  
Emil Svátek ◽  
Antonín Dlabač ◽  
Stanislav Wildt ◽  
Miroslav Protiva
Keyword(s):  
Acetic Anhydride ◽  
Amino Alcohol ◽  
Substitution Reaction ◽  
Antipsychotic Agents ◽  
Substitution Reactions ◽  
Chloro Derivative ◽  
Cns Effects ◽  
Related Compounds ◽  
Depot Antipsychotics ◽  
Hydroxyethyl Piperazine

Substitution reactions of (E)-11-(3-bromopropylidene)-6,11-dihydrodibenzo[b,e]thiepin (VIIIa) and its 2-chloro derivative VIIIb with 1-(2-hydroxyethyl)piperazine gave the title compounds IIIa and IIIb which afforded by treatment with acetic anhydride, decanoyl chloride and 3,4,5-trimethoxybenzoyl chloride the esters IVab-VIab. Reduction of the olefinic compounds IIIa and IIIb with hydrolytic acid resulted in the saturated amines IXa and IXb. The piperazine derivativeX was obtained by a substitution reaction of 2,11-dichloro-6,11-dihydrobenzo[b,e]thiepin with 1-(2-hydroxyethyl)piperazine. The amino alcohols IIIa and IIIb, as well as their acetates and 3,4,5-trimethoxybenzoates, are almost devoid of the CNS effects. The decanates Va and Vb have not the properties of the depot antipsychotics (neither antidepressants, nor neuroleptics). The saturated amino alcohol IXa showed some antihistamine, spasmolytic and adrenolytic effects.

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.

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

1981 ◽  
Vol 46 (8) ◽  
pp. 1800-1807 ◽  
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.

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.

Cyclic amidines derived from benz[c,d]indole and 4,5-dihydro-3H-1-benzazepine including some related compounds: Synthesis and pharmacological screening

1985 ◽  
Vol 50 (8) ◽  
pp. 1888-1898 ◽  
Author(s):  
Miroslav Protiva ◽  
Zdeněk Šedivý ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Jiří Němec
Keyword(s):  
Titanium Tetrachloride ◽  
Aqueous Sodium Hydroxide ◽  
Secondary Amines ◽  
Primary Amines ◽  
Open Chain ◽  
Lithium Aluminium ◽  
Pharmacological Screening ◽  
Antiinflammatory Effects ◽  
Related Compounds ◽  
Sodium Amide

Reactions of naphthostyril (I) with primary and secondary amines and titanium tetrachloride afforded cyclic amidines III-IX. Hydrogenation of I on Pd-C resulted in the 6,7,8,8a-tetrahydro derivative X which gave by treatment with sodium amide and 3-dimethylaminopropyl chloride the N-(aminoalkyl) compound XI. Reduction of I and its N-methyl derivative II with sodium amalgam in aqueous sodium hydroxide gave the 2a,3,4,5-tetrahydro derivatives XII and XIII. Reaction of XIII with sodium amide and 3-dimethylaminopropyl chloride afforded the 2a-(aminoalkyl) compound XIV. 1,3,4,5-Tetrahydro-1-benzazepin-2-one (XV) treated with primary amines and titanium tetrachloride gave the amidines XVI-XVIII. 3-Methyl-7,8,9,9a-tetrahydro-1H-benz[d,e]isoquinoline (XIX) was reduced with sodium borohydride to compound XX which was alkylated with propargyl bromide to 1-methyl-2-propargyl-2,3,3a,4,5,6-hexahydro-1H-benz[d,e]isoquinoline (XXI). An attempt to prepare the 2-(2-phenylethyl) analogue by treatment of compound XX with phenylacetyl chloride and by the following reduction with lithium aluminium hydride resulted in the open-chain amine XXII. The lactams I, II, X, and XIII showed some discoordinating, hypothermic, peripheral vasodilating, hyperglycaemic, diuretic and antiinflammatory effects. The amidines III-IX and XVI-XVIII had local anaesthetic, slight hypotensive, antiarrhythmic, peripheral myorelaxant, papaverine-like spasmolytic and thiopental potentiating effects.

N-substituted aminomethyl 4-cyclopentylphenyl ketones and 2-amino-1-(4-cyclopentylphenyl)ethanol: Synthesis and pharmacological screening

1983 ◽  
Vol 48 (2) ◽  
pp. 642-648 ◽  
Author(s):  
Zdeněk Vejdělek ◽  
Miroslav Protiva
Keyword(s):  
Secondary Amines ◽  
Lithium Aluminium Hydride ◽  
Substitution Reactions ◽  
Rotarod Test ◽  
Lithium Aluminium ◽  
Spontaneous Motility ◽  
Pharmacological Screening ◽  
Higher Doses ◽  
Hydroxyethyl Piperazine ◽  
Ethanol Synthesis

The non-characterized bromo derivative Ia, obtained by bromination of 4-cyclopentylacetophenone, afforded by substitution reactions with diethylamine, benzylmethylamine, benzylisopropylamine, piperidine, morpholine, 1-methylpiperazine and 1-(2-hydroxyethyl)piperazine the amino ketones IIa-VIIIa which were reduced with lithium aluminium hydride to the aminoalcohols IIb-VIIIb. Compounds IIIb and IVb were debenzylated by catalytic hydrogenation on palladium to the secondary amines IXb and Xb. The compounds prepared have central stimulant effects in higher doses which appears also in the rotarod test and in the evaluation of spontaneous motility. They have mostly a mild spasmolytic effect of the anticholinergic type, some of them bring about local anesthetic and diuretic effects. The adrenolytic and hypotensive effects were found only with single compounds.

Sign in / Sign up

Export Citation Format

Share Document