Substituted N,N-Dimethyl-3-(phenylthio)- and -4-(phenylthio)benzylamines

1992 ◽  
Vol 57 (1) ◽  
pp. 194-203 ◽  
Author(s):  
Karel Šindelář ◽  
Vojtěch Kmoníček ◽  
Marta Hrubantová ◽  
Zdeněk Polívka
Keyword(s):  
Serotonin Receptors ◽  
Hydrobromic Acid ◽  
Antidepressant Activity ◽  
Benzoic Acids ◽  
Lithium Aluminium Hydride ◽  
Acid Chlorides ◽  
Activity Inhibition ◽  
Lithium Aluminium ◽  
The Brain

(Arylthio)benzoic acids IIa - IIe and VIb - VId were transformed via the acid chlorides to the N,N-dimethylamides which were reduced either with diborane "in situ" or with lithium aluminium hydride to N,N-dimethyl-(arylthio)benzylamines Ia - Ie and Vb - Vd. Leuckart reaction of the aldehydes IX and X with dimethylformamide and formic acid afforded directly the amines Va and Ve. Demethylation of the methoxy compounds Ia and Ve with hydrobromic acid resulted in the phenolic amines If and Vf. The most interesting N,N-dimethyl-4-(phenylthio)benzylamine (Va) hydrochloride showed affinity to cholinergic and 5-HT2 serotonin receptors in the rat brain and some properties considered indicative of antidepressant activity (inhibition of serotonin re-uptake in the brain and potentiation of yohimbine toxicity in mice).

Synthesis of 1-acyl- and 1-(thioacyl)-4-benzylpiperazines as potential antidepressants

1990 ◽  
Vol 55 (7) ◽  
pp. 1817-1827 ◽  
Author(s):  
Vojtěch Kmoníček ◽  
Emil Svátek ◽  
Jiří Holubek ◽  
Miroslav Ryska ◽  
Martin Valchář ◽  
...  
Keyword(s):  
Benzoic Acid ◽  
Thionyl Chloride ◽  
Antidepressant Activity ◽  
Acid Chlorides ◽  
Phosphorus Pentasulfide ◽  
Antidepressant Agent ◽  
Dimethylaminobenzoic Acid ◽  
Amino Amides

2-Nitro, 3-nitro- and 4-nitrobenzoyl chloride were reacted with 1-benzylpiperazine in benzene in the presence of triethylamine and gave the amides IV-VI, the first of which is considered a bioisostere of the antidepressant agent piberaline (I). 2-Dimethylamino-, 3-dimethylamino- and 4-dimethylaminobenzoic acid were treated with thionyl chloride in benzene in the presence of triethylamine or pyridine, and the acid chlorides formed were reacted in situ with 1-benzylpiperazine affording the amides VII-IX. The amides I and IV-VI were transformed by treatment with phosphorus pentasulfide in pyridine to the thioamides X-XIII. 4-(Dimethylaminomethyl)benzoic acid was reacted with 1-benzylpiperazine in dimethylformamide in the presence of N,N'-carbonyldiimidazole and afforded the amide XIV. Heating of ethyl 5-methylimidazole-4-carboxylate with 1-benzylpiperazine to 200-210 °C gave the amide XV together with the unexpected 1-benzyl-4-ethylpiperazine (XVI). The oily or crystalline bases of the amino amides or thioamides were mostly transformed to crystalline salts and characterized by spectra. Out of the compounds prepared only X (V⁄FB-17 070) and XIV (V⁄FB-17 114) showed indications of efficacy in tests which are considered indicative of antidepressant activity. Compounds VII, VIII, and X appeared to be mildly antidopaminergic - similarly like piberaline (I), and compounds IV, V, XI, XIV, and XV on the contrary showed signs of dopaminominetic activity.

Potential antidepressants: 3-Aryl-3-(arylthio)propylamines as selective inhibitors of 5-hydroxytryptamine re-uptake in the brain

1991 ◽  
Vol 56 (7) ◽  
pp. 1525-1533 ◽  
Author(s):  
Vladimír Valenta ◽  
Marie Vlková ◽  
Martin Valchář ◽  
Karel Dobrovský ◽  
Zdeněk Polívka
Keyword(s):  
Rat Brain ◽  
Antidepressant Activity ◽  
Secondary Amines ◽  
Ethyl Chloroformate ◽  
Selective Inhibitors ◽  
Rat Brain Synaptosomes ◽  
Brain Synaptosomes ◽  
The Brain

4-(Trifluoromethyl)thiophenol, 2-methylthiophenol, 2-methoxythiophenol, and 1-naphthalenethiol were transformed by reactions with N,N-dimethyl-3-chloro-3-phenylpropylamine to N,N-dimethyl-3-aryl-3-(arylthio)propylamines IVa-VIIa. These afforded the secondary amines IVb-VIIb by treatment with ethyl chloroformate and by the following hydrolysis and decarboxylation of the primarily formed N-(methyl)-N-(ethoxycarbonyl) analogues. Reaction of 1-naphthalenethiol with the 4-toluenesulfonic ester X in situ gave the thiophene analogue VIIIa which was similarly demethylated to VIIIb. Some of the prepared compounds (IVa, IVb, Va, VIIIa)were found to be selective inhibitors of 5-hydroxytryptamine re-uptake in the rat brain synaptosomes which indicates their potential antidepressant activity.

Potential antidepressants: 2-(Methoxy- and hydroxyphenylthio)benzylamines as selective inhibitors of 5-hydroxytryptamine re-uptake in the brain

1989 ◽  
Vol 54 (12) ◽  
pp. 3294-3338 ◽  
Author(s):  
Jiří Jílek ◽  
Karel Šindelář ◽  
Josef Pomykáček ◽  
Vojtěch Kmoníček ◽  
Zdeněk Šedivý ◽  
...  
Keyword(s):  
Brain Structures ◽  
Preclinical Studies ◽  
Lithium Aluminium Hydride ◽  
Selective Inhibitors ◽  
Highly Active ◽  
Lithium Aluminium ◽  
Boron Tribromide ◽  
Interesting Compound ◽  
Benzoyl Chlorides ◽  
The Brain

2-, 3- and 4Methoxythiophenol, and 2,4-, 2,5- and 3,4-dimethoxythiophenol were transformed in two steps to the corresponding 2-(methoxyphenylthio)benzoyl chlorides XIII which were reacted with ammonia, methylamine, diethylamine, dipropylamine, and di(2-propyl)amine to give the amides XIV-XIX. These were reduced mostly with lithium aluminium hydride to the amines II-VII. These methoxylated amines were demethylated mostly either by heating with pyridine hydrochloride or by treatment with boron tribromide. Some of the 2-(methoxy- and hydroxy-phenylthio)benzylamines prepared, especially compounds II, III, XXI, and XXII, indicated properties of potential antidepressants being highly active and selective inhibitors of 5-hydroxytryptamine re-uptake in the brain structures and having the typical antireserpine activity. The most interesting compound of the series is XXIb (hydrogen maleate VUFB-15 468) which is undergoing preclinical studies. On the basis of its structure, some further compounds (XXVII–XXIX, XXXIX-XLI) were prepared by various methods.

Potential antidepressants and selective inhibitors of 5-hydroxytryptamine re-uptake in the brain: Synthesis of several potential metabolites of moxifetin and of two A-ring fluorinated analogues

1991 ◽  
Vol 56 (2) ◽  
pp. 459-477 ◽  
Author(s):  
Karel Šindelář ◽  
Josef Pomykáček ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Martin Valchář ◽  
...  
Keyword(s):  
Hydrobromic Acid ◽  
Methanesulfonic Acid ◽  
Brain Structures ◽  
Hydroxyl Group ◽  
Acid Chlorides ◽  
Selective Inhibitors ◽  
Mixed Anhydrides ◽  
The Brain ◽  
Short Heating ◽  
Acid Compound

A series of potential metabolites of the potent inhibitor of 5-hydroxytryptamine re-uptake in the brain structures – moxifetin (I) – i.e. the O-methylated and hydroxylated, further methoxylated, and N-monodemethylated analogues (III – VII, IX, and X) was synthesized from the acids XV, XIX, XXIIIa, XXIIIb, XXVIIa, and XXVIIb. The synthesis of III and V proceeded with protection of one hydroxyl group by benzyl and by the final debenzylation by short heating with hydrobromic acid. Compound IV was obtained by partial demethylation of N,N-dimethyl-(3-,4-dimethoxyphenylthio)benzylamine with sodium 4-toluenethiolate. Synthesis of VI, VII, IX, and X proceeded without protection of the hydroxyl group via the mixed anhydrides of the mentioned acids and methanesulfonic acid which were coupled with dimethylamine and the dimethylamides obtained were directly reduced to the final products. Two A-ring fluorinated analogues of I, i.e. VIII and XI were prepared from the acids XXIIIc and XXVIIc via acid chlorides, dimethylamides, and amines XXVIc and XXXc. The final step was demethylation by heating with hydrobromic acid. The N-oxide XII was obtained by oxidation of I with hydrogen peroxide in ethanol. Compounds III (VUFB-18285) and especially XI (VUFB-17724) were found to be selective inhibitors of the 5-hydroxytryptamine re-uptake in the brain. Some compounds (IV, VI, VII, X) indicate a similar type of activity. In addition to II (described previously), compounds IV and V were found to be moxifetin metabolites in the animals.

Convenient Synthesis of (Z)-7- and (E)-9-dodecene-1-yl Acetate, Components of Some Lepidoptera Insect Sex Pheromone

2017 ◽  
Vol 68 (1) ◽  
pp. 180-185
Author(s):  
Adriana Maria Andreica ◽  
Lucia Gansca ◽  
Irina Ciotlaus ◽  
Ioan Oprean
Keyword(s):  
Sex Pheromone ◽  
Coupling Reaction ◽  
Coupling Scheme ◽  
Lithium Aluminium Hydride ◽  
Terminal Alkyne ◽  
Mercury Derivative ◽  
Lithium Aluminium ◽  
Convenient Synthesis ◽  
Practical Synthesis ◽  
Insect Sex

Were developed new and practical synthesis of (Z)-7-dodecene-1-yl acetate and (E)-9-dodecene-1-yl acetate. The routes involve, as the key step, the use of the mercury derivative of the terminal-alkyne w-functionalised as intermediate. The synthesis of (Z)-7-dodecene-1-yl acetate was based on a C6+C2=C8 and C8+C4=C12 coupling scheme, starting from 1,6-hexane-diol. The first coupling reaction took place between 1-tert-butoxy-6-bromo-hexane and lithium acetylide-ethylendiamine complex obtaining 1-tert-butoxy-oct-7-yne, which is transformed in di[tert-butoxy-oct-7-yne]mercury. The mercury derivative was directly lithiated and then alkylated with 1-bromobutane obtaining 1-tert-butoxy-dodec-7-yne. After acetylation and reduction with lithium aluminium hydride of 7-dodecyne-1-yl acetate gave (Z)-7-dodecene-1-yl acetate with 96 % purity. The synthesis of (E)-9-dodecene-1-yl acetate was based on a C8+C2=C10 and C10+C2=C12 coupling scheme, starting from 1,8-octane-diol. The first coupling reaction took place between 1-tert-butoxy-8-bromo-octane and lithium acetylide-ethylendiamine complex obtaining 1-tert-butoxy-dec-9-yne, which is transformed in di[tert-butoxy-dec-9-yne]mercury. The mercury derivative was directly lithiated and then alkylated with 1-bromoethane obtaining 1-tert-butoxy-dodec-9-yne. After reduction with lithium aluminium hydride of 1-tert-butoxy-(E)-9-dodecene and acetylation was obtained (E)-9-dodecene-1-yl acetate with 97 % purity.

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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