Some 4-Substituted 1-(3-Pyridylmethyl)piperazines with Antihistamine Activity

1994 ◽  
Vol 59 (10) ◽  
pp. 2343-2350 ◽  
Author(s):  
Vojtěch Kmoníček ◽  
Martin Valchář ◽  
Zdeněk Polívka
Keyword(s):  
Acetic Acid ◽  
Nicotinic Acid ◽  
Addition Reaction ◽  
Antidepressant Activity ◽  
Structural Resemblance ◽  
Antihistamine Activity ◽  
Antidepressant Agent ◽  
Pharmacological Testing ◽  
Substituted 1

Several compounds derived from nicotinic acid were prepared within a more extensive programme aiming at the synthesis of new substances with expected antihistamine and antidepressant activity. Some of these compounds display certain structural resemblance with the antidepressant agent piberaline (EGYT 475, Trelibet®, I) and its analogues. The products were used as intermediates for the synthesis of further compounds and most of them were subjected to pharmacological testing. Substituted nicotinic acid piperazides IIa - IId and IVa - IVe were obtained by reactions of nicotinoyl chloride (prepared in situ) with the correspondingly substituted piperazines. Reduction of the piperazides IIa - IId and IVa - IVd with diborane in situ in tetrahydrofuran afforded corresponding 1-substituted 4-(3-pyridylmethyl)piperazines IIIa - IIId and Va - Vd. Whereas the alkylation of 1-(2-pyrimidinyl)piperazine with 2-(chloromethyl)pyridine in ethanol in the presence of triethylamine resulted in compounds Ve, compound Vf was obtained by the addition reaction of 1-(3-pyridylmethyl)piperazine to acrylamide. The piperazides VIe and VIf were prepared by reactions of 2-(3-pyridyl)acetic acid with 1-(2-pyrimidinyl)piperazine or 3-(1-piperazinyl)propionamide in N,N-dimethylformamide in the presence 1,1'-carbonyldiimidazole. A similar procedure starting from nicotinic acid afforded the piperazide IVf. Compounds Vc and Vd showed significant affinity for the histamine H1-receptors (inhibition of binding of 2 nmol/l [3H]mepyramine in membranes from the rat brain: Vc, IC50 = 28 nmol/l; Vd, IC50 = 148 nmol/l). They also proved active in test of histamine aerosol in guinea pigs (PD50 = 4.1 mg/kg p.o. for compound Vc and 2.4 for compound Vd). Results of a more detailed pharmacological testing of these compounds will be published elsewhere.

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.

6,11-Dihydrodibenzo[b,e]thiepin-11-yl 3-quinuclidinyl ethers: New potential intidepressants and antihistamine agents

1988 ◽  
Vol 53 (8) ◽  
pp. 1806-1811 ◽  
Author(s):  
Zdeněk Polívka ◽  
Jan Metyš ◽  
Miroslav Protiva
Keyword(s):  
Methyl Derivative ◽  
Antihistamine Activity ◽  
Antidepressant Agent ◽  
Anticataleptic Activity

Reactions of 11-chloro-6,11-dihydrodibenzo[b,e]thiepin and its 2-methyl derivative, and further of the methanesulfonates of 2-chloro- and 2-bromo-6,11-dihydrodibenzo[b,e]thiepin-11-ol with 3-quinuclidinol afforded the title ethers I-IV. The 2-methyl compound II (VÚFB-17 088) showed significant antihistamine activity and the 2-chloro compound III (VÚFB-17 089), having antireserpine and anticataleptic activity, proved a potential antidepressant agent.

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).

Acetic acid mediated regioselective synthesis of 2,4,5-trisubstituted thiazoles by a domino multicomponent reaction

2019 ◽  
Vol 43 (22) ◽  
pp. 8644-8650 ◽  
Author(s):  
Mohit Saroha ◽  
Jitender M. Khurana
Keyword(s):  
Acetic Acid ◽  
Multicomponent Reaction ◽  
Regioselective Synthesis ◽  
Domino Reaction ◽  
Thiazole Derivatives ◽  
Active Methylene

Acetic acid mediated regioselective synthesis of novel 2,4,5-trisubstituted thiazole derivatives has been reported by a domino reaction of thiosemicarbazide and aldehydes/ketones/isatin, to generate thiosemicarbazones (in situ) followed by addition of arylglyoxal and active methylene/activated C–H acids/pyrazole/indole in ethanol at 80 °C.

ChemInform Abstract: Some 4-Substituted 1-(3-Pyridylmethyl)piperazines with Antihistamine Activity.

ChemInform ◽  
2010 ◽  
Vol 26 (17) ◽  
pp. no-no
Author(s):  
V. KMONICEK ◽  
M. VALCHAR ◽  
Z. POLIVKA
Keyword(s):  
Antihistamine Activity ◽  
Substituted 1

1-Carba-arachno-pentaborane(10) Derivatives

1997 ◽  
Vol 62 (8) ◽  
pp. 1254-1262 ◽  
Author(s):  
Bernd Wrackmeyer ◽  
Hans-Jörg Schanz
Keyword(s):  
High Yield ◽  
Exchange Reactions ◽  
Nmr Data ◽  
Substituted 1 ◽  
C Nmr

The formation of organo substituted 1-carba-arachno-pentaborane(10) derivatives is shown to proceed in high yield via in situ generated 1,1,1-tris(diethylboryl)propane (2) from diethyl(propyn-1-yl)borane (1) by hydroboration with an excess of diethylborane (hydride bath). In the hydride bath, exchange reactions between 2 and other geminal bis(diethylboryl)alkanes take place until the carbaborane skeleton is formed. If tris(diethylboryl)methane is used under the same conditions, the corresponding 1-carba-arachno-pentaborane(10) derivatives 11 and 12 are formed in mixture with other unknown boranes or carboranes. 11B and 13C NMR data are presented to allow for straightforward identification of the 1-carba-arachno-pentaboranes(10).

Development of novel sourdoughs with in situ formed exopolysaccharides from acetic acid bacteria

2015 ◽  
Vol 241 (2) ◽  
pp. 185-197 ◽  
Author(s):  
Maria Hermann ◽  
Hannes Petermeier ◽  
Rudi F. Vogel
Keyword(s):  
Acetic Acid ◽  
Acetic Acid Bacteria

Instabilities in the System NMMO/Water/Cellulose (Lyocell Process) Caused by Polonowski Type Reactions

Holzforschung ◽  
2002 ◽  
Vol 56 (2) ◽  
pp. 199-208 ◽  
Author(s):  
Thomas Rosenau ◽  
Antje Potthast ◽  
Andreas Hofinger ◽  
Herbert Sixta ◽  
Paul Kosma
Keyword(s):  
Molecular Weight ◽  
Acetic Acid ◽  
Exchange Resin ◽  
Degradation Products ◽  
Ion Exchange Resin ◽  
Low Molecular Weight ◽  
Acid Component ◽  
Degradation Reactions ◽  
Polyglucuronic Acid

Summary Polonowski type degradation reactions are a major reason for the frequently observed instability of solutions of cellulose in N-methylmorpholine-N-oxide monohydrate (NMMO, 1). The degradation is induced by degradation products of cellulose and NMMO generated in situ in the Lyocell system. The presence of both an amine component, such as morpholine or N-methylmorpholine, and an acid component is required for the decomposition process to proceed. The latter might be a low-molecular-weight compound, such as formic acid, acetic acid or gluconic acid, or also a high-molecular-weight acid, such as polyglucuronic acid or ion exchange resin.

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