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.

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.

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.

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.

Synthesis, Docking Study, Cytotoxicity, Antioxidant, and Anti-microbial Activities of Novel 2,4-Disubstituted Thiazoles Based on Phenothiazine

2020 ◽  
Vol 17 (2) ◽  
pp. 151-159
Author(s):  
Tran Nguyen Minh An ◽  
Pham Thai Phuong ◽  
Nguyen Minh Quang ◽  
Nguyen Van Son ◽  
Nguyen Van Cuong ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Antimicrobial Activities ◽  
Significant Activity ◽  
Thiazole Derivatives ◽  
Ligand Interaction ◽  
Ic50 Value ◽  
Mcf 7

: A series of novel 1,3-thiazole derivatives (5a-i) with a modified phenothiazine moiety were synthesized and tested against cancer cell line MCF-7 for their cytotoxicity. Most of them (5a-i) were less cytotoxic or had no activity against MCF-7 cancer cell line. Material and Methods: The IC50 value of compound (4) was 33.84 μM. The compounds (5a-i) were also evaluated for antimicrobial activities, but no significant activity was observed. The antioxidant activity was conducted for target compounds (5a-i). The IC50 value of compound (5b) was 0.151mM. Results: The total amount of energy, ACE (atomic contact energy), energy of receptor (PDB: 5G5J), and ligand interaction of structure (4) were found to be 22.448 Kcal.mol-1 , -247.68, and -91.91 Kcal.mol-1, respectively. The structure (4) is well binded with the receptor because the values of binding energy, steric energy, and the number of hydrogen bondings are -91.91, 22.448 kcal.mol-1, and 2, respectively. It shows that structure (4) has good cytotoxicity with MCF-7 in vitro. Conclusion: The increasing of docking ability of structures (5a-i) with the receptor is presented in increasing order as (5f)>(5e)>(5g)>(5a)>(5b)>(5d)>(5c)>(5i)>(5h). The structure bearing substitution as thiosemicarbazone (4), nitrogen heterocyclic (5f), halogen (5e), and azide (5g) showed good cytotoxicity activity in vitro.

Synthesis of Novel 3(N,N-dialkylamino)alkyl/phenyl Substituted Thieno [2,3-d]pyrimidinones as H1-Anti-Histaminic and Antimicrobial Agents

2019 ◽  
Vol 15 (1) ◽  
pp. 63-70
Author(s):  
Shiv Dev Singh ◽  
Arvind Kumar ◽  
Firoz Babar ◽  
Neetu Sachan ◽  
Arun Kumar Sharma
Keyword(s):  
Antimicrobial Activity ◽  
Potassium Hydroxide ◽  
Antimicrobial Agents ◽  
Pyrimidine Ring ◽  
Antimicrobial Activities ◽  
Screening Methods ◽  
Chlorpheniramine Maleate ◽  
In Vivo Screening

Background: Thienopyrimidines are the bioisoster of quinazoline and unlike quinazoline exist in three isomeric forms corresponding to the three possible types annulation of thiophene to the pyrimidine ring viz thieno[2,3-d] pyrimidine, thieno[3,2-d] pyrimidine and thieno[3,4-d]pyrimidine. Heterocyclic containing the thienopyrimidinone moiety exhibits various pronounced activities such as anti-hypertensive, analgesic and anti-inflammatory, antiviral, platelet aggregation inhibitory, antiprotozoal bronchodilatory, phosphodiesterase inhibitory, antihistaminic, antipsychotic and antimicrobial activity. Objective: Synthesis of novel 3(N,N-dialkylamino)alkyl/phenyl substituted thieno[2,3-d]pyrimidinones as H1-anti-histaminic and antimicrobial agents. Methods: A series of 3-[(N,N-dialkylamino)alkyl/phenyl]-2-(1H)thioxo-5,6,7,8-tetrahydrobenzo(b) thieno(2,3-d)pyrimidine-4(3H)-ones[4a-d], their oxo analogous [5a-d] and 3-[(N,N-dialkylamino)alkyl]- 2-chlorophenyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d)pyrimidine- 4 (3H)-ones[6a-d]derivative were synthesized from 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carboxylic acid by nucleophilic substitution of different N,N-dialkyl alkylene/phenylene diamines on activated 3-acylchloride moiety followed by cyclocondensation with carbon disulfide and ethanolic potassium hydroxide to get [4a-d] and in second reaction by condensation with 4-chlorobenzoyl chloride to get [6a-d] by single pot novel innovative route. The oxo analogous [5a-d] were prepared by treating derivatives [4a-d] with potassium permagnate in ethanolic KOH. The synthesized compound were evaluated for H1-antihistaminic and antimicrobial activities. Results: All synthesized compounds exhibited significant H1-antihistaminic activity by in vitro and in vivo screening methods and data were verified analytically and statistically. The compound 4a, 4b, 5a and 5b showed significant H1-antihistaminiic activity than the reference standard chlorpheniramine maleate. The compound 6d, 6c, 5c and 4c exhibited significant antimicrobial activity.

Synthesis, Antimicrobial Evaluation and Docking Study of Novel Thiosemicarbazone clubbed with 1,2,3-Triazoles

2020 ◽  
Vol 16 ◽  
Author(s):  
Adinath D. Badar ◽  
Shubham M. Sulakhe ◽  
Mahesh B. Muluk ◽  
Naziya N. M. A. Rehman ◽  
Prashant P. Dixit ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Biological Activities ◽  
Dna Gyrase ◽  
Docking Study ◽  
Antimicrobial Activities ◽  
Diffusion Method ◽  
Molecular Docking Study ◽  
Triazole Derivatives ◽  
Antibacterial And Antifungal

Background: Thiosemicarbazone, 1,2,3-triazole and their derivatives received great pharmaceutical importance due to their prominent biological activities. In the present study, the molecular hybrid thiosemicarbazone-1,2,3-triazoles derivatives were synthesized and screened for their antimicrobial activities. Methods: A series of thiosemicarbazone clubbed with 1,2,3-triazole derivatives were synthesized via click chemistry approach in good yields. The structures of synthesized compounds were assigned by their spectral data. The in vitro antimicrobial activity was performed by the agar well diffusion method. A molecular docking study was performed to identify the possible mode of action of synthesized derivatives. Results: The compounds 5d, 5h, 5i and 5k have exhibited excellent antimicrobial activities against both antibacterial and antifungal pathogens. The active thiosemicarbazone-1,2,3-triazole derivatives have shown excellent binding affinity towards DNA gyrase. Conclusion: The molecular hybrid thiosemicarbazone-1,2,3-triazole derivatives were synthesized. The newly synthesized compounds were evaluated for their antimicrobial activities. Few of the thiosemicarbazone-1,2,3-triazoles derivatives have exhibited good antimicrobial activities. They have been shown excellent binding affinity towards DNA gyrase.

In-vitro Antimicrobial Activities of Pongamia glabra and Phyllanthus niruri

2016 ◽  
Vol 2 (2) ◽  
pp. 236 ◽  
Author(s):  
N. Mahalakshmi ◽  
S. Dhanasekaran ◽  
C. Ravi ◽  
S. Lingathurai
Keyword(s):  
Antimicrobial Activities ◽  
Phyllanthus Niruri ◽  
Pongamia Glabra

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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