Synthesis and Analgesic Activity of Some Substituted 1-Benzofurans and 1-Benzothiophenes

[img]PDF - Authorized users only
Language: English
138Kb
Title:Synthesis and Analgesic Activity of Some Substituted 1-Benzofurans and 1-Benzothiophenes
Creators:
Rádl, Stanislav
Hezký, Petr
Konvička, Petr
Krejčí, Ivan
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 65, 7, pp. 1093-1108
Uncontrolled Keywords:Antinociceptive activity, Demethylations, Analgesics, Alkylations, Heterocyclizations, Benzothiophenes, Benzofurans

Abstract

2-Benzoyl- and 2-(pyridylcarbonyl)-1-benzofuran-3-amines were prepared from 2-hydroxybenzonitrile and corresponding bromoethanone derivatives. 2-Benzoyl- and 2-(pyridylcarbonyl)-1-benzothiophene-3-amines were prepared analogously from 2-sulfanylbenzonitrile. 2-Benzoyl-1-benzofuran-3-amine treated with acetic anhydride or ethyl chloroformate provided the corresponding <i>N</i>-acetyl or <i>N</i>-ethoxycarbonyl derivatives. These <i>N</i>-activated compounds were alkylated with ethyl bromoacetate to provide ethyl <i>N</i>-acetyl-<i>N</i>-(2-benzoyl-1-benzofuran-3-yl)glycinate and ethyl <i>N</i>-(2-benzoyl-1-benzofuran-3-yl)-<i>N</i>-ethoxycarbonylglycinate, respectively. Their mild hydrolysis gave the corresponding glycine derivatives. Methylation of ethyl <i>N</i>-(2-benzoyl-1-benzofuran-3-yl)carbamate gave the corresponding <i>N</i>-methyl carbamate, which was hydrolyzed to <i>N</i>-methyl-(2-benzoyl-1-benzofuran-3-yl)amine. 2-Benzoyl-7-methoxy-1-benzofuran-3-amine and 2-(4-methoxybenzoyl)-1-benzofuran-3-amine were demethylated with boron tribromide to the corresponding hydroxy derivatives; their <i>O</i>-alkylation with ethyl bromoacetate than gave ethyl [(3-amino-2-benzoyl-1-benzofuran-7-yl)oxy]acetate and ethyl {4-[(3-amino-1-benzofuran-2-yl)carbonyl]phenoxy}acetate, respectively. The mild hydrolysis of these esters provided corresponding acids. Similarly, alkylation of the hydroxy derivatives with (dimethylamino)propyl chloride gave corresponding (dimethylamino)propoxy derivatives. 2-Hydroxybenzonitrile treated with 2-bromo-1-(2-, 3-, or 4-pyridyl)ethan-1-one provided the respective 2-(pyridylcarbonyl)-1-benzofuran-3-amine. Similar 2-(pyridylcarbonyl)-1-benzothiophene-3-amines were prepared analogously from 2-sulfanylbenzonitrile. 2-Benzoyl-3-(bromomethyl)-1-benzofuran treated with dimethylamine, 1-methylpiperazine, and sodium 1-methylpiperidine-4-thiolate gave the corresponding alkylation products. Several compounds were found to exhibit considerable analgesic activity. <p>

Title:Synthesis and Analgesic Activity of Some Substituted 1-Benzofurans and 1-Benzothiophenes
Creators:
Rádl, Stanislav
Hezký, Petr
Konvička, Petr
Krejčí, Ivan
Uncontrolled Keywords:Antinociceptive activity, Demethylations, Analgesics, Alkylations, Heterocyclizations, Benzothiophenes, Benzofurans
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:65
Number:7
Page Range:pp. 1093-1108
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20001093UNSPECIFIED
ID Code:1703
Item Type:Article
Deposited On:06 Feb 2009 17:11
Last Modified:06 Feb 2009 16:12

Citation

Rádl, Stanislav; Hezký, Petr; Konvička, Petr; Krejčí, Ivan (2000) Synthesis and Analgesic Activity of Some Substituted 1-Benzofurans and 1-Benzothiophenes. Collection of Czechoslovak Chemical Communications, 65 (7). pp. 1093-1108. ISSN 0010-0765

Repository Staff Only: item control page