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Synthesis and Quantitative Structure-Property Relationships of Side Chain-Modified Hyodeoxycholic Acid Derivatives
TES Pharma S.r.l., Via P. Togliatti, 20, Loc Taverne, 06073 Corciano, Italy
Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Via del Liceo, 1, 06123 Perugia, Italy
* Author to whom correspondence should be addressed.
Received: 9 July 2013; in revised form: 21 August 2013 / Accepted: 27 August 2013 / Published: 30 August 2013
(This article belongs to the Special Issue Steroids
Abstract: Bile acids have emerged as versatile signalling compounds of a complex network of nuclear and membrane receptors regulating various endocrine and paracrine functions. The elucidation of the interconnection between the biological pathways under the bile acid control and manifestations of hepatic and metabolic diseases have extended the scope of this class of steroids for in vivo investigations. In this framework, the design and synthesis of novel biliary derivatives able to modulate a specific receptor requires a deep understanding of both structure-activity and structure-property relationships of bile acids. In this paper, we report the preparation and the critical micellization concentration evaluation of a series of hyodeoxycholic acid derivatives characterized by a diverse side chain length and by the presence of a methyl group at the alpha position with respect to the terminal carboxylic acid moiety. The data collected are instrumental to extend on a quantitative basis, the knowledge of the current structure-property relationships of bile acids and will be fruitful, in combination with models of receptor activity, to design and prioritize the synthesis of novel pharmacokinetically suitable ligands useful in the validation of bile acid-responsive receptors as therapeutic targets.
Keywords: bile acids; structure-property relationships; critical micellization concentration
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Sabbatini, P.; Filipponi, P.; Sardella, R.; Natalini, B.; Nuti, R.; Macchiarulo, A.; Pellicciari, R.; Gioiello, A. Synthesis and Quantitative Structure-Property Relationships of Side Chain-Modified Hyodeoxycholic Acid Derivatives. Molecules 2013, 18, 10497-10513.
Sabbatini P, Filipponi P, Sardella R, Natalini B, Nuti R, Macchiarulo A, Pellicciari R, Gioiello A. Synthesis and Quantitative Structure-Property Relationships of Side Chain-Modified Hyodeoxycholic Acid Derivatives. Molecules. 2013; 18(9):10497-10513.
Sabbatini, Paola; Filipponi, Paolo; Sardella, Roccaldo; Natalini, Benedetto; Nuti, Roberto; Macchiarulo, Antonio; Pellicciari, Roberto; Gioiello, Antimo. 2013. "Synthesis and Quantitative Structure-Property Relationships of Side Chain-Modified Hyodeoxycholic Acid Derivatives." Molecules 18, no. 9: 10497-10513.