119138-47-5Relevant articles and documents
Diastereo- and enantioselective bioreduction of ethyl 2-(4-chlorophenoxy)- 3-oxobutanoate clofibrate analogues by Kluyveromyces marxianus and other whole cell biocatalysts
Perrone, Maria Grazia,Santandrea, Ernesto,Scilimati, Antonio,Syldatk, Christoph,Tortorella, Vincenzo,Capitelli, Francesco,Bertolasi, Valerio
, p. 3511 - 3517 (2004)
Growing and resting cells of several yeasts, which catalyze the hydride transfer to a carbonyl, were screened and used in conditions to find out the suitable methodology to prepare clofibrate analogues. Clofibrate is an antilipidemic drug. In particular, the bioreduction of ethyl 2-(4-chlorophenoxy)-3-oxobutanoate 1 was investigated to separately prepare the four possible stereoisomers of the ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate 2. Compound (2R,3S)-2 was prepared with ee = 97% and 73% yield in the presence of Kluyveromyces marxianus; (2S,3S)-2 preparation with ee >99% in 9% and 33% yield was mediated by Saccharomyces cerevisiae CBS 7336 and Trigonopsis variabilis, respectively. Diastereomeric excess values of all the reactions investigated were up to >99%. Furthermore, enantiomeric excesses of the bioconversions varied between 2% and >99% using growing cells and, 12% and >99% using resting cells. The absolute configuration of (2R,3S)-2 was established by X-ray analysis of the corresponding acid 3.
Synthesis and biological evaluation of new clofibrate analogues as potential PPARα agonists
Perrone, Maria Grazia,Santandrea, Ernesto,Dell'Uomo, Natalina,Giannessi, Fabio,Milazzo, Ferdinando Maria,Sciarroni, Anna Floriana,Scilimati, Antonio,Tortorella, Vincenzo
, p. 143 - 154 (2007/10/03)
Clofibrate is a lipid-profile modifying agent belonging to the fibrate class of drugs. Fibrates are known to exhibit their beneficial effects by activating peroxisome proliferator-activated receptor-α (PPARα) and used in the treatment of dyslipidemia and atherosclerosis and for the prevention of heart failure. Hereby, the preparation of two new sets of clofibrate analogues, ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates and ethyl 2-(4-chlorophenoxy)-3-hydroxyalkanoates is described starting from commercially available 3-oxoalkanoates in fair to good yields. Treatment of 3-oxoalkanoates with SO2Cl2 yielded the corresponding 2-chloro-3- oxoalkanoates, that were then converted into 2-(4-chlorophenoxy)-3-oxoalkanoates by reacting with sodium or caesium 4-chlorophenate. Reduction of the keto group with NaBH4 afforded the corresponding 2-(4-chlorophenoxy)-3- hydroxyalkanoates in very high yields and with variable diastereoselectivity. Biological evaluation of the compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. The newly synthesised clofibrate analogues failed to show noticeable levels of PPAR activation at concentrations where clofibrate showed an evident activity, suggesting that the structural modifications caused the loss of PPAR activity.
α-adrenergic receptor antagonists
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, (2008/06/13)
α-adrenoceptor antagonists having the formula: STR1 which are useful to produce α-adrenoceptor antagonism, pharmaceutical compositions including these antagonists, and methods of using these antagonists to produce α-adrenoceptor antagonism in mannals.