Potential antitussives: Synthesis and pharmacology of a series of 1-[2-amino-2-(4-fluorophenyl)ethyl]-4-(2-benzoylpropyl)piperazines

1983 ◽  
Vol 48 (10) ◽  
pp. 2977-2988 ◽  
Author(s):  
Zdeněk Vejdělek ◽  
Miroslav Protiva
Keyword(s):  
Sodium Borohydride ◽  
Thionyl Chloride ◽  
Amino Alcohol ◽  
Guinea Pigs ◽  
Potassium Hydroxide ◽  
Substitution Reactions ◽  
Mannich Reactions ◽  
Central Depression ◽  
Higher Doses

Compound V, obtained by a reaction of 2-chloro-4'-fluoroacetophenone with 1-(ethoxycarbonyl)piperazine, was reduced with sodium borohydride to the amino alcohol VIf. The hydrochloride of VIf was treated with thionyl chloride to give the hydrochloride of 1-[2-chloro-2-(4-fluorophenyl)ethyl]-4-(ethoxycarbonyl)piperazine (VIg). The crude VIg was subjected to substitution reactions with diethylamine, pyrrolidine, piperidine, morpholine and 1-methylpiperazine in benzene at 60 °C. The obtained aminocarbamates VIa-VIe were hydrolyzed with concentrated ethanolic potassium hydroxide and gave the amines VIIa-VIIe. Mannich reactions of the hydrochlorides of these compounds with paraformaldehyde and propiophenone (and 4-hydroxypropiophenone, respectively) resulted in the title compounds IIIa-IIIe, IVa,b and IVd,e. Only substances IIIa and IIId were found to have an antitussic activity in rats and guinea-pigs comparable to that of eprazinone (I). In higher doses they brought about central depression, ataxia and ptosis in mice and some of them adrenolytic and hypotensive effects in rats.

4-Substituted 1-(1-(2-(arylthio)-5-halogenophenyl)ethyl)piperazines; Synthesis and biological screening

1987 ◽  
Vol 52 (4) ◽  
pp. 1062-1072 ◽  
Author(s):  
Vladimír Valenta ◽  
Jiří Holubek ◽  
Miroslav Protiva
Keyword(s):  
Sodium Borohydride ◽  
Thionyl Chloride ◽  
Helminth Species ◽  
Secondary Alcohols ◽  
Substitution Reactions ◽  
Biological Screening ◽  
Substituted 1

Reactions of 2,5-dichloroacetophenone and 2,5-dibromoacetophenone with a series of thiophenols gave the 2-(arylthio)-5-halogenoacetophenones VII and VIII which were reduced with sodium borohydride in ethanol to the secondary alcohols IX and X. Treatment with thionyl chloride afforded the chloro compounds XI and XII which were transformed by substitution reactions with correspondingly monosubstituted piperazines by two methods to the title compounds I-V. Their salts (maleates and hydrochlorides) showed in addition to antitussic activity some anthelmintic effects towards a series of the helminth species.

Involvement of 5-Hydroxytryptamine in Platelet Aggregation In Vivo in Rats and Guinea Pigs

1989 ◽  
Vol 61 (03) ◽  
pp. 463-467 ◽  
Author(s):  
G M Smith
Keyword(s):  
Platelet Count ◽  
Guinea Pigs ◽  
Platelet Adhesion ◽  
Adenosine Diphosphate ◽  
Rate Of Return ◽  
Low Doses ◽  
Dose Dependent ◽  
Higher Doses ◽  
Rat Platelets

SummaryIn this study, 5-hydroxytryptamine (5-HT) caused a dose- dependent fall in the circulating platelet count suggesting that 5-HT receptors are activated in rat platelets to cause platelet adhesion and aggregation. When low doses of adenosine diphosphate (ADP) were simultaneously injected with 5-HT, there was a significant potentiation of the responses to ADR Ketanserin significantly reduced the potentiated responses. When higher doses of ADP were infused with bolus injections of 5-HT there was no potentiation and ketanserin did not reduce these responses. Ketanserin did not inhibit the collagen-induced fall in circulating platelet count, but did significantly increase the rate of return to the basal platelet count compared with control. 5-HT did not cause a fall in platelet count in guinea-pigs

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.

An Efficient, Large-Scale Synthesis of Cytenamide

2018 ◽  
Vol 42 (3) ◽  
pp. 153-155
Author(s):  
Colin T. Bedford
Keyword(s):  
Sodium Borohydride ◽  
Thionyl Chloride ◽  
Large Scale ◽  
Large Scale Synthesis ◽  
Nitrile Hydrolysis

Dibenzosuberenone (5 H-dibenzo[a,d]cyclohepten-5-one) was reduced to the corresponding alcohol by sodium borohydride/MeOH and converted to the corresponding 5-chloro compound by thionyl chloride/benzene, treatment of which with CuCN/toluene gave the corresponding nitrile. Hydrolysis by ethanolic KOH yielded the corresponding amide, cytenamide (5 H-dibenzo[a,d]cycloheptene-5-carboxamide).

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.

Reactions of N-substituted 2-aminopyridines with chloroacetyl chloride; Formation of a new series of heterocyclic betaines: 1-Substituted 4-chloromethyl-2-oxopyrido[1,2-a]pyrimidin-5-ium-3-olates

1989 ◽  
Vol 54 (5) ◽  
pp. 1376-1387 ◽  
Author(s):  
Hana Hulinská ◽  
Miloš Buděšínský ◽  
Jiří Holubek ◽  
Oluše Matoušová ◽  
Hana Frycová ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Sodium Borohydride ◽  
Nmr Spectra ◽  
Aqueous Ethanol ◽  
Hydrogen Bromide ◽  
Chloroacetyl Chloride ◽  
Gastric Lesions ◽  
Substitution Reactions ◽  
Reaction Compound ◽  
C Nmr

N-(2-Pyridyl)-2-chloroacetamide reacted with 1-methylpiperazine and gave the expected compound III. Attempts at preparing the N-substituted N-(2-pyridyl)-2-chloroacetamides by reactions of N-substituted 2-aminopyridines with chloroacetyl chloride in benzene in the presence of N,N-dimethylacetamide were negative and took an unexpected course. 2-Anilinopyridine and 2-(cyclohexylamino)pyridine afforded compounds which were identified by 1H and 13C NMR spectra as the heterocyclic betaines IVa and IVb. 2-(1-Butylamino)pyridine, 2-(benzylamino)pyridine and 2-(2-phenylethylamino)pyridine gave similarly compounds IVc-IVe. The chloromethyl compounds IVa-IVe underwent normal substitution reactions with 1-methylpiperazine and gave the methylpiperazino compounds Va-Ve. Attempts to reduce the betaines with sodium borohydride in aqueous ethanol proceeded in one case as the hydrogenolytic displacement of the chlorine atom with hydrogen (product VIa), in another case as ethanolysis (product VIIb). Formation of VIb by treatment of IVb with hydrogen bromide in boiling acetic acid is probably the result of a disproportionation reaction. Compound III (dimaleate VÚFB-17 103) was practically equipotent with pirenzepine (I) as an anti-ulcer agent in the test of indomethacine-induced gastric lesions in rats but was much weaker in tests for antocholinergic and antisecretory activity.

Potential noncataleptic neuroleptic agents: Synthesis and pharmacology of 7-chloro-4-[4-(2-hydroxyethyl)piperazino]-4,5-dihydrothieno[2,3-b]-1-benzothiepin

1983 ◽  
Vol 48 (10) ◽  
pp. 2970-2976 ◽  
Author(s):  
Zdeněk Polívka ◽  
Martin Valchář ◽  
Miroslav Protiva
Keyword(s):  
Sodium Borohydride ◽  
Potassium Carbonate ◽  
Title Compound ◽  
Potassium Hydroxide ◽  
Dopamine Metabolism ◽  
High Dose ◽  
Chloro Derivative ◽  
Hydroxyethyl Piperazine ◽  
Central Depressant ◽  
Boiling Toluene

Heating of 2,5-dichloroacetophenone with 2-thiophenethiol, potassium carbonate and copper gave 5-chloro-2-(2-thienylthio)acetophenone (V) which was subjected to the Willgerodt reaction with sulphur and morpholine. The product was a mixture of the thiomorpholide VI and oxothiomorpholide VII. After a partial separation the predominanting product VI was hydrolyzed without characterization with ethanolic potassium hydroxide to give the acid VIII. Cyclization by treatment with phosphorus pentoxide in boiling toluene gave 7-chlorothieno[2,3-b]-1-benzothiepin-4(5H)-one (X) which was reduced with sodium borohydride to the alcohol XII. A reaction with hydrogen chloride in benzene led to the chloro derivative XIII whose substitution reaction with 1-(2-hydroxyethyl)piperazine afforded the title compound IV. The product has strong central depressant and discoordinating activity, a low cataleptic efficity but in a relatively high dose it does not influence the dopamine metabolism in the rat brain.

scholarly journals The effect of ouabain on metabolic rate in guinea-pigs: estimation of energy cost of sodium pump activity

1989 ◽  
Vol 61 (3) ◽  
pp. 467-473 ◽  
Author(s):  
R. Swaminathan ◽  
Ellen L. P. CHAN ◽  
Liu Yuet Sin ◽  
Ng Siu King ◽  
Ng Sui Fun ◽  
...  
Keyword(s):  
Body Weight ◽  
Metabolic Rate ◽  
Energy Cost ◽  
Guinea Pigs ◽  
Sodium Pump ◽  
Maximal Inhibition ◽  
Percentage Decrease ◽  
Pump Activity ◽  
Higher Doses ◽  
Different Doses

1. The effect of different doses of ouabain, an inhibitor of the sodium pump, or saline (9 g sodium chloride/1; the vehicle) on the metabolic rate of guinea-pigs weighing 500 g was measured by indirect calorimetry for 120 min.2. Ouabain (0·02–0·07 nmol/g body-weight) decreased the oxygen consumption in a dose-related manner. When higher doses of ouabain (0·10 nmol/g body-weight or greater) were injected the animals were observed to shiver. Ouabain (0.07 nmol/g body-weight) reduced Na+, K+-ATPase (EC3. 6. 1. 3) activity of liver, kidney and skeletal muscle by 18·0 (se 6·6), 21.5 (se 6·0) and 21·9 (se 6·8)% respectively. An Eadie-Hofstee plot of percentage decrease in O2consumptionv.percentage inhibition ÷ dose of ouabain showed that maximal inhibition of O2consumption was 39·4 %.3. It is concluded that Na pump activity contributed to about 40 % of the resting O2consumption.

scholarly journals Evaluation of an Alkaline Fuel Cell for Multifuel System

2005 ◽  
Vol 2 (4) ◽  
pp. 234-237 ◽  
Author(s):  
A. Verma ◽  
A. K. Jha ◽  
S. Basu
Keyword(s):  
Activated Carbon ◽  
Fuel Cell ◽  
Power Density ◽  
Current Density ◽  
Sodium Borohydride ◽  
Potassium Hydroxide ◽  
Maximum Power ◽  
Carbon Paper ◽  
Maximum Power Density ◽  
Alkaline Fuel Cell

The performance of an alkaline fuel cell (AFC) is investigated using three different fuels, e.g., methanol, ethanol, and sodium borohydride. Pt∕C∕Ni was used as anode, whereas MnO2∕C∕Ni was used as standard (Electro-Chem-Technic, UK) cathode for all the fuels. Fresh mixture of electrolyte, potassium hydroxide (5M), and fuel (2M) was fed to AFC and withdrawn at a rate of 1ml∕min. The anode was prepared by dispersing platinum and activated carbon in Nafion® (DuPont USA) dispersion and placing it onto a carbon paper (Lydall, USA). Finally prepared anode material was pressed onto Ni mesh and sintered to produce the required anode. The maximum power density of 16.5mW∕cm2 is obtained at 28mA∕cm2 of current density for sodium borohydride at 25°C, whereas methanol produces 31.5mW∕cm2 of maximum power density at 44mA∕cm2 of current density at 60°C. The results obtained showed that the AFC could accept multifuels.

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