Chiral Forms of 4-(2',4'-Difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic Acid (Flobufen) and Its Metabolite.Synthesis and Basic Biological Properties

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Title:Chiral Forms of 4-(2',4'-Difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic Acid (Flobufen) and Its Metabolite.Synthesis and Basic Biological Properties
Creators:
Kuchař, Miroslav
Poppová, Marie
Jandera, Antonín
Panajotovová, Vladimíra
Zůnová, Hana
Buděšínský, Miloš
Tomková, Hana
Jegorov, Alexandr
Taimr, Jan
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 62, 3, pp. 498-509
Uncontrolled Keywords:Synthesis, Antiinflammatory activity, Human metabolite, Chiral forms, Flobufen

Abstract

4-(2',4'-Difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid (<strong>1</strong>, flobufen) is subjected to clinical testing in the treatment of rheumatoid arthritis. Owing to the occurrence of a centre of chirality, the compound exists in two enantiomers, and its major human metabolite, <i>viz</i>. 4-(2',4'-difluorobiphenyl-4-yl)-4-hydroxy-2-methylbutanoic acid isolated in the lactone form (<strong>2</strong>), possesses two chiral centres, making possible the existence of four stereoisomers. All of the optical isomers of the substances <strong>1</strong> and <strong>2</strong> were prepared. For flobufen (<strong>1</strong>), the racemate was separated into the stereoisomers by using the salts <strong>3</strong> with <i>R</i>-(+)- or <i>S</i>-(-)-1-phenylethylamine. The pairs of stereoisomers of <strong>2</strong>, obtained by reduction of <i>R</i>-(+)-flobufen or the <i>S</i>-(-)-enantiomer, were separated by column chromatography. The physico-chemical parameters of the optical isomers were determined and some biological activities were evaluated in both <i>in vitro</i> and <i>in vivo</i> models.

Title:Chiral Forms of 4-(2',4'-Difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic Acid (Flobufen) and Its Metabolite.Synthesis and Basic Biological Properties
Creators:
Kuchař, Miroslav
Poppová, Marie
Jandera, Antonín
Panajotovová, Vladimíra
Zůnová, Hana
Buděšínský, Miloš
Tomková, Hana
Jegorov, Alexandr
Taimr, Jan
Uncontrolled Keywords:Synthesis, Antiinflammatory activity, Human metabolite, Chiral forms, Flobufen
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:62
Number:3
Page Range:pp. 498-509
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19970498UNSPECIFIED
ID Code:1134
Item Type:Article
Deposited On:06 Feb 2009 17:06
Last Modified:06 Feb 2009 16:07

Citation

Kuchař, Miroslav; Poppová, Marie; Jandera, Antonín; Panajotovová, Vladimíra; Zůnová, Hana; Buděšínský, Miloš; Tomková, Hana; Jegorov, Alexandr; Taimr, Jan (1997) Chiral Forms of 4-(2',4'-Difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic Acid (Flobufen) and Its Metabolite.Synthesis and Basic Biological Properties. Collection of Czechoslovak Chemical Communications, 62 (3). pp. 498-509. ISSN 0010-0765

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