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.

(6,11-Dihydrodibenzo[b,e]thiepin-11-yl)methylamine, (4-methoxy-6,11-dihydrodibenzo[b,e]thiepin-11-yl)-methylamine and derivatives; Synthesis and pharmacological screening

1982 ◽  
Vol 47 (3) ◽  
pp. 984-993 ◽  
Author(s):  
Vladimír Valenta ◽  
Jan Metyš ◽  
Miroslav Protiva
Keyword(s):  
Formic Acid ◽  
Alkaline Hydrolysis ◽  
Antiinflammatory Activity ◽  
Primary Amines ◽  
Lithium Aluminium Hydride ◽  
Lithium Aluminium ◽  
Methyl Derivatives ◽  
Curtius Reaction ◽  
Pharmacological Screening

Using the Curtius reaction, the acids VIa and VIv were transformed to the carbamates IVa and IVb which afforded by alkaline hydrolysis the primary amines Ia and Ib. The N-methyl derivatives IIab were obtained by reduction of the carbamates IVa with lithium aluminium hydride. The N,N-dimethyl derivatives IIIab resulted by methylation of the primary amines Iab with formaldehyde and formic acid. The synthesis of the acid VIb was carried out from phthalide and 2-methoxythiophenol in seven steps. The amines Iab-IIIab showed clear thymoleptic properties in the test of reserpine ptosis in mice and by inhibition of the perphenazine catalepsy in rats. The acid VIb has antiinflammatory activity.

Potential antidepressants: 1-(2-(Methoxy- and hydroxyphenylthio)phenyl)-2-propylamines

1990 ◽  
Vol 55 (4) ◽  
pp. 1077-1098 ◽  
Author(s):  
Jiří Urban ◽  
Zdeněk Šedivý ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Miroslav Ryska ◽  
...  
Keyword(s):  
Ethyl Formate ◽  
Secondary Amines ◽  
Primary Amines ◽  
Alternative Route ◽  
Lithium Aluminium Hydride ◽  
Tertiary Amines ◽  
Lithium Aluminium ◽  
Boron Tribromide ◽  
Pharmacological Testing ◽  
By Products

2-(Methoxyphenylthio)benzaldehydes Xa-Xd were reacted with nitroethane in boiling acetic acid to give the corresponding 1-aryl-2-nitropropenes XIIa-XIId; benzonitriles XIIIa and XIIIc and benzaldoximes XXIc and XXId were isolated as by-products. Chromatographed compounds XIIa-XIId were reduced with lithium aluminium hydride to the primary amines VIIa-VIId, and formylated by heating with ethyl formate to the formamides XIVa, XIVc, and XIVd. Reduction of the formamides with lithium aluminium hydride afforded the secondary amines VIIIa, VIIIc, and VIIId, and methylation of the primary amines with formic acid and formaldehyde gave the tertiary amines IXa, IXc, and IXd. Compound VIIIa was prepared also by an alternative route starting from the nitrile XIIIa and proceeding via XIXa and XIVa. Some of the methoxylated amines were demethylated either by heating with pyridine hydrochloride or by treatment with boron tribromide to the title compounds IVa, IVc, Vc, Vd, VIa, and VIc. The amines prepared were transformed to salts for characterization and for pharmacological testing. Compound VIIIa (hydrogen oxalate V⁄FB-15 475) showed clearly the character of a potential antidepressant.

Reactivity of triformylmethane. I. Reactions of triformylmethane with selected types of amino compounds

1991 ◽  
Vol 56 (5) ◽  
pp. 1019-1031 ◽  
Author(s):  
Zdeněk Arnold ◽  
Miloš Buděšínský ◽  
Magdalena Pánková
Keyword(s):  
Lewis Acids ◽  
Secondary Amines ◽  
Primary Amines ◽  
Carbamic Acid ◽  
Sulfonic Acids ◽  
Primary Products ◽  
Amino Compounds ◽  
Related Compounds

Reactions of triformylmethane with various types of amino compounds were investigated. Besides with ammonia, triformylmethane reacts spontaneously with primary amines, aminoacids and their esters, urea and related compounds including carbamic acid derivatives. Reactions with amides of carboxylic and sulfonic acids require catalysis with Lewis acids. Primary products are aminomethylenemalonaldehyde derivatives IIIa-IIIv. Reactions of triformylmethane with excess of selected primary amines and two secondary amines (dimethylamine and morpholine) were also studied.

Synthesis and pharmacological screening of 1-[2-tert-aminoethyl]-8-fluoro-5-[4-fluorophenyl]-2,3,4,5-tetrahydro-1H-1-benzazepines, their 1-[aminoacetyl] analogues and 1-substituted 9-fluoro-6-[4-fluorophenyl]-5,6-dihydro-4H-s-triazolo[4,3-a]-1-benzazepines

1981 ◽  
Vol 46 (1) ◽  
pp. 148-160 ◽  
Author(s):  
Zdeněk Vejdělek ◽  
Emil Svátek ◽  
Jiří Holubek ◽  
Jan Metyš ◽  
Marie Bartošová ◽  
...  
Keyword(s):  
Secondary Amines ◽  
Lithium Aluminium Hydride ◽  
Phosphorus Pentasulfide ◽  
Lithium Aluminium ◽  
High Doses ◽  
Pharmacological Screening ◽  
Central Depressant

7-Fluoro-4-(4-flurophenyl)-1-naphthylamine (III) was identified as a by-product in the transformation of 7-fluoro-4-(4-fluorophenyl)-1-tetralone oxime to the lactam I. Reaction of 8-fluoro-5-(4-flurophenyl)-2,3,4,5-tetrahydro-1H-1-benzazepine (V) with chloracetyl chloride gave the chloramide VI which was treated with secondary amines to give the aminoacetamides VII, VIII, XI and XII. reduction with lithium aluminium hydride afforded the amines IX, X, XIV and XV. Acylation of the piperazinoethanols XII and XV led to the esters XIII, XVI and XVII. Reaction of the lactam I with phosphorus pentasulfide gave the thiolactam II which was treated with a series of acid hydrazides and gave the title compounds XVIII-XXIV. Some of the compounds exhibited only in relatively high doses anticonvulsant and central depressant effects in various tests.

scholarly journals FLUORESCENCE OF CATECHOL AMINES AND RELATED COMPOUNDS CONDENSED WITH FORMALDEHYDE

1962 ◽  
Vol 10 (3) ◽  
pp. 348-354 ◽  
Author(s):  
B. FALCK ◽  
N.-Å. HILLARP ◽  
G. THIEME ◽  
A. TORP
Keyword(s):  
Heterocyclic Ring ◽  
Secondary Reaction ◽  
Secondary Amines ◽  
Primary Amines ◽  
Hydroxyl Groups ◽  
Protein Film ◽  
Mild Conditions ◽  
Catechol Amines ◽  
Formaldehyde Vapour ◽  
Related Compounds

The reaction under mild conditions between formaldehyde and phenylalanine and phenylethylamine derivatives has been studied. When the amines included in a dried protein film were exposed to formaldehyde vapour a very intense green to yellow fluorescence was give only by those that as well as being primary amines also have hydroxyl groups at the 3 and 4 positions (3,4-dihydroxyphenylalanine, dopamine, noradrenaline). The 3-OH group seems to be esssential for the reaction. The catechol amines, which are secondary amines (adrenaline, epinine), gave a much weaker fluorescence that developed more slowly. The results obtained on further examination of the reaction favour the view that the amines primarily condense with formaldehyde to 1,2,3,4-tetrahydroisoquinolines which are involved in a secondary reaction to become highly fluorescent and at the same time insoluble. This secondary reaction may be a binding to protein, and oxidation with the formation of double bonds in the heterocyclic ring, or both.

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.

Acceptorless amine dehydrogenation and transamination using Pd-doped layered double hydroxides

2018 ◽  
Author(s):  
Diana Ainembabazi ◽  
Nan An ◽  
Jinesh Manayil ◽  
Kare Wilson ◽  
Adam Lee ◽  
...  
Keyword(s):  
Layered Double Hydroxides ◽  
Oxidation States ◽  
Secondary Amines ◽  
Primary Amines ◽  
Acid Dissolution ◽  
Oxidative Amination ◽  
Strong Function ◽  
Excellent Activity ◽  
High Yields ◽  
Double Hydroxides

<div> <p>The synthesis, characterization, and activity of Pd-doped layered double hydroxides (Pd-LDHs) for for acceptorless amine dehydrogenation is reported. These multifunctional catalysts comprise Brønsted basic and Lewis acidic surface sites that stabilize Pd species in 0, 2+, and 4+ oxidation states. Pd speciation and corresponding cataytic performance is a strong function of metal loading. Excellent activity is observed for the oxidative transamination of primary amines and acceptorless dehydrogenation of secondary amines to secondary imines using a low Pd loading (0.5 mol%), without the need for oxidants. N-heterocycles, such as indoline, 1,2,3,4-tetrahydroquinoline, and piperidine, are dehydrogenated to the corresponding aromatics with high yields. The relative yields of secondary imines are proportional to the calculated free energy of reaction, while yields for oxidative amination correlate with the electrophilicity of primary imine intermediates. Reversible amine dehydrogenation and imine hydrogenation determine the relative imine:amine selectivity. Poisoning tests evidence that Pd-LDHs operate heterogeneously, with negligible metal leaching; catalysts can be regenerated by acid dissolution and re-precipitation.</p> </div> <br>

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.

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