1-(4-Cyclopentylphenyl)piperazine and its 4-substituted derivatives; Synthesis and biological screening

1987 ◽  
Vol 52 (7) ◽  
pp. 1834-1840 ◽  
Author(s):  
Zdeněk Vejdělek ◽  
Miroslav Protiva
Keyword(s):  
Antimicrobial Activity ◽  
Benzyl Chloride ◽  
Addition Reaction ◽  
Anthelmintic Activity ◽  
Ethyl Formate ◽  
Lithium Aluminium Hydride ◽  
Biological Screening ◽  
Acyl Chlorides ◽  
Lithium Aluminium

Heating the hydrochlorides of 4-cyclopentylaniline and diethanolamine to 250 °C gave 1-(4-cyclopentylphenyl)piperazine (I). Acylation of I with ethyl formate and the corresponding acyl chlorides gave the amides II, VI, and VII which were reduced with lithium aluminium hydride to the piperazines III, VIII, and IX. Treatment of I with benzyl chloride and with 4-chloro-1-(4-fluorophenyl)butan-1-one under different conditions led to compounds IX and XI. Addition reaction of I to 1,2-epoxybutane resulted in the amino alcohol V. The products showed marginal tranquillizing activity (especially compound VIII), some antimicrobial activity in vitro and some anthelmintic activity.

Potential antidepressants: 2-(Phenylthio)aralkylamines

1989 ◽  
Vol 54 (7) ◽  
pp. 1995-2008 ◽  
Author(s):  
Jiří Jílek ◽  
Jiří Urban ◽  
Petr Taufmann ◽  
Jiří Holubek ◽  
Antonín Dlabač ◽  
...  
Keyword(s):  
Nmr Spectra ◽  
Benzyl Chloride ◽  
Lithium Aluminium Hydride ◽  
Pharmacological Profile ◽  
H Nmr ◽  
Lithium Aluminium ◽  
Alternative Approach ◽  
Phenyl Acetonitrile ◽  
Claisen Reaction ◽  
Pharmacological Testing

Reactions of 2-(phenylthio)benzyl chloride with dimethylamine, diethylamine, pyrrolidine, piperidine, morpholine, and 1-methylpiperazine afforded the title compounds VI-XI. Reaction of 2-(phenylthio)benzaldehyde with nitromethane gave the nitrostyrene XIV which was reduced with lithium aluminium hydride to 2-(2-(phenylthio)phenyl)ethylamine (XVI). This was transformed to the N-methyl and N,N-dimethyl derivatives XVIII and XIX. The Claisen reaction of (2-(phenylthio)phenyl)acetonitrile with ethyl acetate afforded compound XXI which was cleaved by phosphoric acid to (2-(phenylthio)phenyl)acetone (XX). The Leuckart-Wallach reaction afforded the formamide XXIII which was used as starting material for preparing the amines XXIV-XXVI. The alternative approach to these compounds starting by reaction of the aldehyde XII with nitroethane was complicated by the fact that in addition to the nitropropene XV 2-(phenylthio)benzonitrile was also formed. The synthetic use of the inhomogeneous XV resulted then in mixtures of amines XXIV-XXVI with IV-VI which was followed by means of mass and 1H NMR spectra. The amines XXIV-XXVI were oxidized to the sulfoxides XXVII-XXIX. The oily bases were transformed to crystalline salts and spectra of all homogeneous bases were recorded. Pharmacological testing showed the amine VI (VÚFB-15 370) to be a promising potential antidepressant. The amines XI and XXV showed also pharmacological profile of potential antidepressants.

scholarly journals Design, Synthesis and In Vitro Characterization of Novel Antimicrobial Agents Based on 6-Chloro-9H-carbazol Derivatives and 1,3,4-Oxadiazole Scaffolds

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 266 ◽  
Author(s):  
Alexandra T. Bordei Telehoiu ◽  
Diana C. Nuță ◽  
Miron T. Căproiu ◽  
Florea Dumitrascu ◽  
Irina Zarafu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Oral Absorption ◽  
Phosphorus Oxychloride ◽  
In Vitro Cytotoxicity ◽  
Mutagenic Potential ◽  
Design Synthesis ◽  
Acyl Chlorides ◽  
Hydrazide Derivative

In this paper, we aimed to exploit and combine in the same molecule the carbazole and the 1,3,4-oxadiazole pharmacophores, to obtain novel carprofen derivatives, by using two synthesis pathways. For the first route, the following steps have been followed: (i) (RS)-2-(6-chloro-9H-carbazol-2-yl)propanonic acid (carprofen) treatment with methanol, yielding methyl (RS)-2-(6-chloro-9H-carbazol-2-yl)propanoate; (ii) the resulted methylic ester was converted to (RS)-2-(6-chloro-9H-carbazol-2-yl)propane hydrazide (carprofen hydrazide) by treatment with hydrazine hydrate; (iii) reaction of the hydrazide derivative with acyl chlorides led to N-[(2RS)-2-(6-chloro-9H-carbazol-2-yl)propanoil]-N′-R-substituted-benzoylhydrazine formation, which; (iv) in reaction with phosphorus oxychloride gave the (RS)-1-(6-chloro-9H-carbazol-2-yl)-1-(1,3,4-oxadiazol-2-yl)ethane derivatives. In the second synthesis pathway, new 1,3,4-oxadiazole ring compounds were obtained starting from carprofen which was reacted with isoniazid, in the presence of phosphorus oxychloride to form (RS)-1-(6-chloro-9H-carbazol-2-yl)-1-[5-(4-pyridyl)-1,3,4-oxadiazol-2-yl]ethane. The synthesized compounds were characterized by IR, 1H-NMR and 13C-NMR, screened for their drug-like properties and evaluated for in vitro cytotoxicity and antimicrobial activity. The obtained compounds exhibited a good antimicrobial activity, some of the compounds being particularly active on E. coli, while others on C. albicans. The most significant result is represented by their exceptional anti-biofilm activity, particularly against the P. aeruginosa biofilm. The cytotoxicity assay revealed that at concentrations lower than 100 μg/mL, the tested compounds do not induce cytotoxicity and do not alter the mammalian cell cycle. The new synthesized compounds show good drug-like properties. The ADME-Tox profiles indicate a good oral absorption and average permeability through the blood brain barrier. However, further research is needed to reduce the predicted mutagenic potential and the hepatotoxicity.

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.

Synthesis and biological evaluation of newer 1,3,4-oxadiazoles incorporated with benzothiazepine and benzodiazepine moieties

2017 ◽  
Vol 72 (3-4) ◽  
pp. 133-146 ◽  
Author(s):  
Patel Navin ◽  
Patel Sarvil ◽  
Purohit Amit ◽  
Patel Divyesh ◽  
Rajani Dhansukh ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Giardia Lamblia ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Leishmania Mexicana ◽  
Aspergillus Clavatus ◽  
Biological Screening ◽  
Synthesis And Biological Evaluation

Abstract A series of thiazepines and diazepines having 1,3,4-oxadiazole moiety were synthesized, and they were analyzed for their in vitro antimicrobial activity against several bacteria (Staphylococcus aureus, Staphylococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa) and fungi (Candida albicans, Aspergillus niger, and Aspergillus Clavatus) and protozoa (Entamoeba histolytica, Giardia lamblia, Trypanosoma cruzi and Leishmania mexicana). Few of the selected compounds were tested for their antitubercular activity. However, it was noticed that the potency of final analogs against each strain placed reliance on the type of substituent present on aryl ring of oxadiazole as well as presence of thiophene, pyridine, and furan at benzothiazepines and benzodiazepines. The biological screening identified that some of the compounds were found to possess good antimicrobial and antitubercular (62.5–100 μg/mL of MIC) activity.

Preparation of Phosphonomethyl Ethers Derived from 2-Phenylethanol and Its Amino Derivatives

1995 ◽  
Vol 60 (4) ◽  
pp. 659-669
Author(s):  
Marcela Krečmerová ◽  
Antonín Holý
Keyword(s):  
Antiviral Activity ◽  
Cell Cultures ◽  
Sodium Hydride ◽  
Amino Group ◽  
Lithium Aluminium Hydride ◽  
Adenine Ring ◽  
Lithium Aluminium ◽  
Amino Derivatives ◽  
Acyclic Nucleoside

A series of compounds derived from the acyclic nucleoside antiviral 9-(2-phosphonomethoxyethyl)adenine (PMEA), in which the adenine ring is replaced by phenyl, 4-aminophenyl, 3-aminophenyl or 3,5-diaminophenyl group, has been prepared starting from the corresponding phenethyl alcohols. 2-(3-Aminophenyl)ethanol was prepared from 3-nitrobenzoyl chloride using the Arndt-Eistert reaction. The primarily formed diazoketone Ia was converted into ethyl 3-nitrophenylacetate (IIa) which on catalytic hydrogenation afforded ethyl 3-aminophenylacetate (IIIa). Compound IIIa was reduced with lithium aluminium hydride to give 2-(3-aminophenyl)ethanol (IVa). 2-(3,5-Diaminophenyl)ethanol (IVb) was prepared analogously from 3,5-dinitrobenzoyl chloride. After protection of the amino group with dimethylaminomethylene group, the alcohol IVa was converted to diisopropyl 2-(3-aminophenyl)ethoxymethylphosphonate (XII) by reaction with sodium hydride and diisopropyl p-toluenesulfonyloxymethanephosphonate, followed by deprotection of the amino group by treatment with ammonia. Reaction of diisopropyl ester XII with bromotrimethylsilane gave free 2-(3-aminophenyl)ethoxymethylphosphonic acid (XVII). The same procedure, applied to the corresponding aminophenethyl alcohols, afforded: 2-(4-aminophenyl)ethoxymethylphosphonic acid (XVI) and 2-(3,5-diamino phenyl)ethoxymethylphosphonic acid (XVIII). The synthesized compounds were tested in vitro on cell cultures for the cytostatic and antiviral activity (HSV-1, HSV-2, VSV, VZV, CMV). No antiviral activity has been found for any of the compounds.

scholarly journals SYNTHESIS, CHARACTERIZATION, IN VITRO ANTIMICROBIAL, ANTHELMINTIC AND DOCKING STUDIES OF NEW 2-[(E)-{[4-(1H-1,2,4-TRIAZOL-1 YLMETHYL)PHENYL]IMINO} METHYL]PHENOL, AND THEIR COMPLEXES WITH 3D METAL IONS

2016 ◽  
Vol 8 (9) ◽  
pp. 134
Author(s):  
Jithendra Kumara K.s. ◽  
Krishnamurthy G. ◽  
Sunil Kumar N.
Keyword(s):  
Antimicrobial Activity ◽  
Schiff Base ◽  
Transition Metal ◽  
Metal Complexes ◽  
Transition Metal Complexes ◽  
Research Work ◽  
Anthelmintic Activity ◽  
Triazole Ring ◽  
Diffusion Method

<p><strong>Objective: </strong>The main objectives of this research work is the synthesis and characterization of biologically potential triazole ring containing the Schiff base legend and their transition metal complexes, followed by screenings of their antimicrobial and anthelmintic activity the results of antimicrobial activity were compared with docking scores.</p><p><strong>Methods: </strong>The<strong> </strong>coordination complexes of Co(II), Cu(II), Fe(III) and Zn(II) with Schiff base derived ligand 4-(1<em>H</em>-1,2,4-triazol-1-ylmethyl) aniline and substituted aldehydes have been synthesized. The complexes are characterized by elemental analysis, conductivity measurements, electronic, IR, and <sup>1</sup>H NMR spectral data. The synthesized compounds were also screened <em>In vitro</em> antimicrobial activity was carried out according to diffusion method by using agar and potato dextrose agar at 100, 500 and 700 mg/ml concentrations in DMF.<strong> </strong>HEX 8.0<strong> </strong>programmers were used to perform the docking experiments on <em>nucleotide </em>of <em>S. typhi </em><em>at</em> as ligand [PDB: 3B6O].</p><p><strong>Results: </strong>Schiff base ligand and their transition metal complexes were studied for antimicrobial activity as well as docking. The results of both studies concluded that 4a, 4c and 4d compounds are more active in minimum inhibition concentration (30μg/ml) against <em>Staphylococcus aureus</em> (<em>S. aureus), Salmonella typhi (S. typlei)</em> bacteria and <em>Penicillium chrysogenum</em> (<em>P. Crysogenum) </em>fungi. The compounds showed highest docking score (-257.47,-275.61 and-280.17 respectively) with the secondary structure of the alpha-amylase with a nucleotide from <em>s. typhi</em> in the solid model. In the study of anthelmintic activity among these three compounds, 4d compound exhibits more activity compared with the standard.</p><strong>Conclusion: </strong>The compounds 4a, 4c and 4d were found to be more promising pharmacological activity this observation may promote a further development of this triazole group of compounds which may lead to better pharmacological profile than standard drugs. <p> </p>

Synthesis of 24-(Piperidin-1-yl, Morpholin-4-yl and 4-Methylpiperazin-1-yl)-5β-cholan-3α-ols and Four Hydroxylated 23-(4,5-Dihydroimidazol-2-yl)-24-nor-5β-cholanes

1997 ◽  
Vol 62 (3) ◽  
pp. 471-478 ◽  
Author(s):  
Thi Thu Huong Nguyen ◽  
Jiří Protiva ◽  
Eva Klinotová ◽  
Jiří Urban ◽  
Miroslav Protiva
Keyword(s):  
Cholic Acid ◽  
Acid Chloride ◽  
Antimicrobial Activities ◽  
Spectral Characterization ◽  
Lithium Aluminium Hydride ◽  
Lithium Aluminium

Lithocholic (1a), chenodeoxycholic (1b), deoxycholic (1c) and cholic acid (1d) were used for the synthesis of the title compouds. Reactions of O-acetyllithocholic acid chloride with piperidine, morpholine and 1-methylpiperazine gave the corresponding amides 2a-2c which were reduced with lithium aluminium hydride to 24-(piperidin-1-yl)-5β-cholan-3α-ol (3a) and analogues 3b and 3c. Heating of the acids 1a-1d with ethylenediamine monotosylate afforded 23-(4,5-dihydroimidazol-2-yl)-24-nor-5β-cholan-3α-ol (4a) and analogues 4b-4d. Compound 4a was similarly obtained from 3α-acetoxy-24-nor-5β-cholane-23-carbonitrile. Identity of the products was corroborated by spectral characterization. Some of the products (in the form of salts) were tested for cancerostatic and antimicrobial activities in vitro with partially promising results.

scholarly journals Synthesis and In Vitro Antimicrobial and Anthelminthic Evaluation of Naphtholic and Phenolic Azo Dyes

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Joseph Kwasi Adu ◽  
Cedric Dzidzor Kodjo Amengor ◽  
Nurudeen Mohammed Ibrahim ◽  
Cynthia Amaning-Danquah ◽  
Charles Owusu Ansah ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Anthelmintic Activity ◽  
Salmonella Typhi ◽  
Systematic Investigation ◽  
Pathogenic Microorganisms ◽  
Inhibition Assay ◽  
Growth Inhibition Assay ◽  
Culture Growth

The antimicrobial activity of 2-naphtholic and phenolic azo compounds was determined against seven microbial species, Staphylococcus aureus (ATCC 25923), Streptococcus pyrogenes (clinical), and Enterococcus faecalis (ATCC 29212), Salmonella typhi (clinical), Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 251922), and Candida albicans (ATCC 10231), using the high-throughput spot culture growth inhibition assay (HT-SPOTi). The minimum inhibitory concentrations (MIC) were determined for the active azo dyes. All the azo compounds (A1–B4) were screened for anthelmintic activity against adult Ghanaian earthworms, Hyperiodrilus spp. As part of the systematic investigation for biological activity, all the azo compounds exhibited good antimicrobial activity against the seven human pathogenic microorganisms. All the compounds exhibited anthelminthic activity against adult Ghanaian earthworms, Hyperiodrilus spp.

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