Indol-2-Carboxylic Acid Esters Containing N-Phenylpiperazine Moiety - Preparation and Cholinesterase-inhibiting Activity

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62157124%3A16370%2F20%3A43878590" target="_blank" >RIV/62157124:16370/20:43878590 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14160/20:00118112

Result on the web

<a href="https://www.eurekaselect.com/182943/article" target="_blank" >https://www.eurekaselect.com/182943/article</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1570179417666200619132218" target="_blank" >10.2174/1570179417666200619132218</a>

Result language

angličtina

Original language name

Indol-2-Carboxylic Acid Esters Containing N-Phenylpiperazine Moiety - Preparation and Cholinesterase-inhibiting Activity

Original language description

Background: The indole derivatives and the N-phenylpiperazine fragment represent interesting molecular moieties suitable for the research of new potentially biologically active compounds. This study was undertaken to identify if indol-2-carboxylic acid esters containing N-phenylpiperazine moiety possess acetyleholinesterase and butyrylcholinesterase inhibitory activity. Materials and Methods: The study dealt with the synthesis of a novel series of analogs of 1H-indole-2-carboxylic acid and 3-methyl-1H-indole-2-carboxylic acid. The structure of the derivatives was represented by the indolylcarbonyloxyaminopropanol skeleton with the attached N-phenylpiperazine or diethylamine moiety, which formed a basic part of the molecule. The final products were synthesized as dihydrochloride salts, fumaric acid salts, and quaternary ammonium salts. The first step of the synthetic pathway led to the preparation of esters of 1H-indole-2-carboxylic acid from the commercially available 1H-indole-2-carboxylic acid. The Fischer indole synthesis was used to synthesize derivatives of 3-methyl-1H-indole-2-carboxylic acid. Results and Discussion: Final 18 indolylcarbonyloxyaminopropanols in the form of dihydrochlorides, fumarates, and quaternary ammonium salts were prepared using various optimization ways. The very efficient way for the formation of 3-methyl-1H-indole-2-carboxylate (Fischer indole cyctization product) was the one-pot synthesis of phenylhydrazine with methyl 2-oxobutanoate with acetic acid and sulphuric acid as catalysts. Conclusion: Most of the derivatives comprised of an attached N-phenylpiperazine group, which formed a basic part of the molecule and in which the phenyl ring was substituted in position C-2 or C-4. The synthesized compounds were subjected to cholinesterase-inhibiting activity evaluation, by modified Ellman method. Quaternary ammonium salt of 1H-indole-2-carboxylic acid which contain N-phenylpiperazine fragment with nitro group in position C-4 (7c) demonstrated the most potent activity against acetylcholinesterase.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Current organic synthesis

ISSN

1570-1794

e-ISSN

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Volume of the periodical

17

Issue of the periodical within the volume

7

Country of publishing house

AE - UNITED ARAB EMIRATES

Number of pages

12

Pages from-to

576-587

UT code for WoS article

000590858900009

EID of the result in the Scopus database

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