Synthesis of N-(1-phenyl-2-propyl)-2,5-diphenylpentylamine and some related compounds as potential neurotropic and cardiovascular drugs

1986 ◽  
Vol 51 (7) ◽  
pp. 1487-1493 ◽  
Author(s):  
Zdeněk Vejdělek ◽  
Jiří Němec ◽  
Miroslav Protiva
Keyword(s):  
Butyric Acid ◽  
Cardiovascular Drugs ◽  
Lithium Aluminium Hydride ◽  
Dibutyl Ether ◽  
Lithium Aluminium ◽  
Related Compounds ◽  
Antiarrhythmic Effects

Heating of 2,5-diphenylvaleric acid with 2-phenylethylamine, 1-phenyl-2-propylamine, 1-phenyl-2-butylamine (IX), 1-(4-methoxyphenyl)-2-propylamine, 1-(4-methoxyphenyl)-2-butylamine (X) and 1-(4-dimethylaminophenyl)-2-propylamine to 200-210 °C resulted in the amides IIb-VIIb which were reduced with lithium aluminium hydride in boiling dibutyl ether to give the amines IIa, IIIa, and Va - VIIa. A similar two-step sequence starting from 4-phenyl-4-(phenylthio)-butyric acid and the amine IX gave compound VIIIa. The salts of the title amines revealed some central stimulating, antireserpine, thiopental potentiating, anticonvulsant, and antiarrhythmic effects. 1-(4-Dimethylaminophenyl)-2-butylamine (XI), prepared in this connection, proved anoretic activity.

1-[2-(2-Hydroxymethylphenylthio)benzyl]-4-methylpiperzine and related compounds as potential antidepressants: Synthesis and pharmacological acreening

1984 ◽  
Vol 49 (4) ◽  
pp. 1009-1020 ◽  
Author(s):  
Irena Červená ◽  
Miroslav Protiva
Keyword(s):  
Potassium Carbonate ◽  
Secondary Alcohol ◽  
The Other ◽  
Lithium Aluminium Hydride ◽  
Keto Acid ◽  
Open Model ◽  
Lithium Aluminium ◽  
Neuroleptic Agent ◽  
The One ◽  
Related Compounds

Heating of 1-(2-iodobenzoyl)-4-methylpiperazine (II) with thiophenol and its 2-methyl, 4-methyl, 4-chloro and 2-hydroxymethyl derivatives in dimethylformamide in the presence of potassium carbonate, copper and cuprous iodide gave the piperazides IV-VIII; compound VIII was transformed by reduction with lithium aluminium hydride to the title compound I. The acid IX, obtained by a reaction of 5-chloro-2-iodobenzoic acid with 2-methylthiophenol, was reduced to the alcohol X, which was transformed via the chloride XI to 1-[5-chloro-2-(2-methylphenylthio)-benzyl]-4-methylpiperazine (XII), an open model of the neuroleptic agent clorothepin. Heating of 2,5-dichloroacetophenone with thiosalicylic acid afforded the keto acid XIII whose reaction with 1-methylpiperazine was carried out with the help of N,N"-carbonyldiimidazole. The piperazide XIV obtained was reduced on the one hand with sodium borohydride to the secondary alcohol XV, and with lithium aluminium hydride to 1-(2-[4-chloro-2-(1-hydroxyethyl)phenylthio]benzyl)-4-methylpiperazine (XVI) on the other. None of the dibasic piperazines (I, XII, XVI) did show antireserpine activity. In the general screening, some of the piperazides displayed a mild hypotensive (II, VIII, XIV, XV), adrenolytic (VIII), mild stimulating and antitussic (V), and spasmolytic, antiinflammatory and negatively ino- and chronotropic (XIV) activities.

Tricyclic neuroleptics: Synthesis of metabolites of isofloxythepin and some related compounds

1990 ◽  
Vol 55 (9) ◽  
pp. 2282-2303 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Jílek ◽  
Josef Pomykáček ◽  
Vladimír Valenta ◽  
Marta Hrubantová ◽  
...  
Keyword(s):  
Formic Acid ◽  
Substitution Reaction ◽  
Lithium Aluminium Hydride ◽  
Enol Ether ◽  
Basic Product ◽  
Lithium Aluminium ◽  
Toluenesulfonic Acid ◽  
Neuroleptic Agent ◽  
Related Compounds ◽  
By Products

The isofloxythepin (I) metabolite IV was synthesized via the acids IX and XI and the esters X and XII. The enamine VIII was prepared from 3-fluoro-8-(2-propyl)dibenzo[b,f]thiepin-10(11H)-one by two methods and was reduced to I. Cloflumide (II) was obtained by reaction of 2,10-dichloro-7-fluoro-10,11-dihydrodibenzo[b,f]thiepin with 3-(1-piperazinyl)propionamide and was oxidized to the sulfoxide XVI. The unsaturated analogue XVII of clopithepin (III) was prepared from 2-chlorodibenzo[b,f]thiepin-10(11H)-one by reaction with 2-bromoethanol in the presence of 4-toluenesulfonic acid in boiling benzene and by the following substitution reaction with 2-(1-piperazinyl)ethanol. An improved synthesis of 6-methyldibenzo[b,f]thiepin-10(11H)-one (XIX) was elaborated. The acid XXVII was synthesized and cyclized with polyphosphate ester. A mixture of compounds was formed from which the ketone XXXVI was isolated and processed by reaction with formamide and formic acid at 200 °C. One of the products was characterized as the formamide XXXIII and was reduced with lithium aluminium hydride to a basic product supposed to be XXXIV. A series of by-products was isolated and characterized. The enamine VIII (V⁄FB-17 156) was found to be a strong neuroleptic agent, similar to isofloxythepin (I). The enol ether XVII (V⁄FB-17 733) was characterized as a mild, practically noncataleptic neuroleptic agent.

Synthesis of racemic and optically active erythro- and threo-9-(2,3,4-trihydroxybutyl)adenines and related compounds

1979 ◽  
Vol 44 (2) ◽  
pp. 593-612 ◽  
Author(s):  
Antonín Holý
Keyword(s):  
Sodium Borohydride ◽  
Sodium Salt ◽  
Sodium Periodate ◽  
Optically Active ◽  
Protecting Groups ◽  
Lithium Aluminium Hydride ◽  
Acidic Hydrolysis ◽  
Lithium Aluminium ◽  
Hydrolysis Of ◽  
Related Compounds

Reduction of diethyl 2,3-O-isopropylidene-DL-tartrate (II) with lithium aluminium hydride afforded 2,2-dimethyl-1,3-dioxolane-threo-4,5-dimethanol (III) which was transformed to the monotosyl derivative VI. Reaction of this compound with sodium salt of adenine, followed by acidic deblocking, gave 9-(DL)-threo-(2,3,4-trihydroxybutyl)adenine (IX). Analogously, 9-(DL)-erythro-(2,3,4-trihydroxybutyl)adenine (XVII) was prepared from diethyl meso-tartrate (XI) via the diol XIII and the tosyl derivative XV. 1,3-O-Benzylidene-D-threitol (D-XVIII) was converted successively into the 4-O-tosyl derivative XIX and the 2-O-benzoyl-4-O-tosyl derivative XX. Reaction of the compound XX with sodium salt of adenine, followed by removal of the protecting groups in the intermediate XXI, afforded 9-(D)-threo-(2,3,4-trihydroxybutyl)adenine (D-XXII); analogously, 1,3-O-benzylidene-L-threitol (L-XVIII) was transformed into the 9-(L)-threo-derivative L-XXII. The D-threo-derivative D-XXII was prepared also from 5-O-tosyl-3-O-benzoyl-1,2-O-isopropylidene-α-D-xylofuranoside (XXIII) or from 3-O-benzyl derivative XXIX by condensation with sodium salt of adenine, followed by acidic hydrolysis, degradation of the 1,2-diol grouping by sodium periodate and sodium borohydride, and methanolysis or hydrogenolysis. An analogous procedure was used for preparation of 1-(D)-threo-(2,3,4-trihydroxybutyl)uracil (D-XXVII). Methyl 2,3-O-isopropylidene-5-benzoyl-6-tosyl-D-mannofuranoside (XXXVI) was transformed to the 5-(adenin-9-yl) derivative XXXVII which after hydrolysis of the dioxolane ring, followed by cleavage of the cis-diol with sodium periodate, reduction with sodium borohydride and methanolysis, afforded 9-(D)-erythro-(2,3,4-trihydroxybutyl)adenine (D-XL). The L-enantiomer (L-XL) was obtained from 5-O-(adenin-9-yl)-3-O-benzoyl-1,2-O-isopropylidene-β-L-arabinofuranoside (XXXIIIb) by acidic cleavage, degradation of the intermediate XXXIV with periodate and methanolysis.

The Structure and Function of Oestrogens. II. The Synthesis and Oestrogenic Activity of 4b-Methyl 4b,5,6,12-tetrahydrochrysene-2,8-diol and 4b-Methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol and Related Compounds

1979 ◽  
Vol 32 (5) ◽  
pp. 1107 ◽  
Author(s):  
DJ Collins ◽  
WA Matthews ◽  
GM Stone
Keyword(s):  
Hydrogen Peroxide ◽  
Structure And Function ◽  
Lithium Aluminium Hydride ◽  
Alkaline Hydrogen Peroxide ◽  
Lithium Aluminium ◽  
Methylmagnesium Iodide ◽  
And Function ◽  
Dihydroxy Compound ◽  
Related Compounds

Hydroboration of an inseparable mixture of 2,8-dimethoxy-5,6-dihydrochrysene (5a) and 2,8-dimethoxy-4b-methyl-4b,5,6,12-tetrahydrochrysene (6a) followed by oxidation with alkaline hydrogen peroxide gave a mixture of (4bα,10bβ,11β)-2,8-dimethoxy-4b-methyl-4b,5,6,10a,11,12-hexahydrochrysen-11-ol (10a) and its (4bβ,10bβ,11β) isomer(11a). Reduction of the methanesulfonate ester of (10a) with lithium aluminium hydride in ether gave 2,8-dimethoxy-4b-methyl-trans-4b,5,6,10b,11,12- hexahydrochrysene (2b), identical with material prepared by another route. Reduction of the methanesulfonate of (4bβ,10bβ,l1β)-2,8-dimethoxy-4b-methyl-4b,5,6,10a,11,12-hexahydrochrysen- 11-ol afforded 2,8-dimethoxy-4b-methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene (12), demethylation of which afforded 4b-methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol (14b). Dehydration of the mixture of the 11-epimeric alcohols (10a) and (lla) with phosphorus oxytrichloride in pyridine yielded pure 2,8-dimethoxy-4b-methyl-4b,5,6,12-tetrahydrochrysene (6a) which was demethylated with methylmagnesium iodide to give the corresponding dihydroxy compound (9). Other compounds prepared in the course of examining possible routes to (9) and (14b) include 13,13-dichloro-2,8-dimethoxy-4b,5,6,10b,11,12-hexahydro-4b,10b-methanoch rysene (3a), 1-bromo- 2,8-dimethoxy-5,6-dihydrochrysene (5b), and 11-bromo-2,8-dimethoxy-4b-methy1-4b,5,6,12-tetra- hydrochrysene (7). The oestrogenic activities of some of the new angularly methylated hydrochrysenes and of 9α- methyloestradiol (15) are reported.

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.

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.

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).

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