Structure activity relationship of Taxol

Guenard D, Gueritte-Voegelein F, Dubois J, Potter P. (1993) Structure-activity relationships of taxol and taxotere analogues. J Natl Cancer Inst Monogr 15 79-82. 

Guenard, D., Gueritte-Voegelein, R, Dubois, L, Potier, P. Structure-activity relationships of Taxol and Taxotere analogues. J. Natl. Cancer Inst. Monogr. 1993, 75, 79-82. 

Bioactive conformations, and structure-activity relationship of taxol and its analogs 05ZOR329. Configuration, conformation, reactivity, and applications of hexahydropyrrolo[2,3-b]indoles in synthesis 07ACR151. 

S)mthesis, bioactive conformations, and structure-activity relationship of taxol and its analogs 05ZOR329. 

A number of non-standard side chains have been prepared as part of various ongoing efforts to define the structure-activity relationships of taxol, and these are discussed in this section. 

Several attempts have been made to define the key pharmacophore of taxol. Much of the chemical work reported in the previous sections was carried out with a view to determining structure-activity relationships for taxol and its analogs and thus to defining the pharmacophore in chemical terms. Some of this work can be summarized as in structure 15.4.1 below, where the key structure-activity relationships of taxol are shown. 

Chen S, Farina V, Wei J, Long B, Fairchild C, Mamber SW, Kadow JF, Vyas D, Doyle TW (1994) Structure-Activity Relationships of Taxol Synthesis and Biological Evaluation of C2 Taxol Analogs. Bioorg Med Chem Lett 4 479... 

Kant J, Huang S, Wong H, Fairchild C, Vyas D, VF (1993) Studies toward Structure-Activity Relationships of Taxol Synthesis and Cytotoxicity of Taxol Analogues with C-2 Modified Phenylisoserine Side Chains. Bioorg Med Chem Lett 3 2471... 

The structure-activity relationship of taxol has been studied by a multitude of researchers. The molecule can divide into two parts the side chain and the taxol skeleton. The side chain of taxol is critical for maintaining activity. The stmcture-activity of the side chain has revealed the following features ... 

Since 1985, when the last review in this treatise concerning taxanes was published (3), several new elements concerning the pharmacology and therapeutic use of taxol have appeared. Moreover, knowledge of the structure-activity relationships of this class of compounds has been broadened with the discovery of promising analogs. 

Ojima I, Fenoglio I, Park YH, Sun C-M, Appendino G, Pera P, Bemacki RJ (1994) Synthesis and Structure-Activity Relationships of Novel Nor-Seco Analogs of Taxol and Taxotere. J Org Chem 59 515... 

In this chapter, we describe an account of our research on the chemistry and biology of paclitaxel and taxoid anticancer agents (taxoid = taxol-like compound). The topics covered in this chapter include (i) the development of a practical and efficient method for the semisynthesis of paclitaxel and docetaxel using chiral 3-hydroxy-P-lactams as synthetic intermediates, (ii) structure-activity relationship (SAR) studies of various taxoids that led to the discovery of the extremely potent second-generation taxoids, and (iii) biological and conformational studies with the use of fluorine-containing taxoids as probes. ... 

The second chapter addresses new facets of the medicinal chemistry of the important anticancer drug Taxol (paclitaxel). Ojima and coworkers explore, in particular, the structure-activity relationship associated with the 3-phenylisoserine side chain, synthetically exploiting their P-Lactam Synthon Method . Their research has led to, among other things, a series of noteworthy second-generation taxoid anticancer agents. 

Structure/activity relationship studies on the sarcodictyin library are performed by induction of tubulin polymerization and by cytotoxicity studies with three cancer cell lines, including Taxol-resistant lines. Derivatives that induce tubulin polymerization more strongly than the natural product sarcodictyin have been determined, and can show higher cytotoxicity even as far as Taxol-resistant tumor cells are concerned. The results of the structure/... 

Chen, S.-H. Fairchild, C. Mamber, S. W. Farina, V. Taxol structure-activity relationships synthesis and biological evaluation of 10-deox3daxol. J. Org. Chem., 1993, 58 2927-2928. 

Since the discovery of taxol in 1971, a large number of analogues have been extracted or synthesized. An attempt to tabulate these derivatives in order to extrapolate structure-activity relationships would be pointless as the structural... 

Most studies of structure activity relationships (SAR) rely on degradations of baccatin and semisynthesis. [1, 3, 4] First insights into the SAR of taxol derivatives have been summerized in a recent article on C ring aryl derivatives, [4] and more can be expected in the near future as patented information becomes released. Total synthesis, especially in preparing the way for the synthesis of derivatives, will be of great importance to elucidate the relationship between structure, microtubuli stabilization and anticancer activity more thoroughly. This impact of total syn-... 

The synthesis of taxol or docetaxel requires the coupling of a protected side chain with a protected baccatin III. The procedures for this have not changed significantly since the previous review in this series, but some points of interest have emerged. The semisynthesis of taxol has been reviewed relatively recently (295), and the first section has thus been abbreviated. In addition, since the focus of this review is on the chemistry of taxol rather than its medicinal chemistry and structure-activity relationships, the sections dealing with the syntheses of taxol analogs will present illustrative rather than exhaustive examples. 

Two additional reviews on taxol chemistry and biology have been published. One covers its history and gives an overview of its chemistry (572), and the other surveys recent aspects of its chemistry and structure-activity relationships (575). A recent book recounts the history of the development of taxol as a drug, with an emphasis on the difficulties of the supply problem and the controversial agreement with Bristol-Myers Squibb to commercialize it (574). 

Chen S-H, Wei J-M, Farina V (1993) Taxol Structure-Activity Relationships Synthesis and Biological Evaluation of 2-Deoxytaxol. Tetrahedron Lett 34 3205... 

Gueritte-Voegelein, R Guenard, D. Lavelle, R Le Goff, M.-T. Mangatal, L. Potier, P. Relationships between the structure of taxol analogs and their antimitotic activity. J. Med. Chem., 1991, 34 992-998. 

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