103258-64-6Relevant articles and documents
An alternative synthetic route for an antidiabetic drug, rosiglitazone
Jawale, Dhanaji V.,Pratap, Umesh R.,Mane, Ramrao A.
, p. 924 - 928 (2012)
A convenient and scalable four-step novel route has been developed for the synthesis of rosiglitazone (8), an antidiabetic drug. This multistep route requires 4-fluoro benzaldehyde (4), 2,4-thiazolidinedione (6) and 2-chloro pyridine (1) as key reactants and gives overall better yield of rosiglitazone. In addition, some steps have been accelerated, which leads to an overall time saving of 10 h.
Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)
Linciano, Pasquale,Benedetti, Rosaria,Pinzi, Luca,Russo, Fabiana,Chianese, Ugo,Sorbi, Claudia,Altucci, Lucia,Rastelli, Giulio,Brasili, Livio,Franchini, Silvia
, (2020/11/24)
Histone Deacetylases (HDACs) are among the most attractive and interesting targets in anticancer drug discovery. The clinical relevance of HDAC inhibitors (HDACIs) is testified by four FDA-approved drugs for cancer treatment. However, one of the main drawbacks of these drugs resides in the lack of selectivity against the different HDAC isoforms, resulting in severe side effects. Thus, the identification of selective HDACIs represents an exciting challenge for medicinal chemists. HDACIs are composed of a cap group, a linker region, and a metal-binding group interacting with the catalytic zinc ion. While the cap group has been extensively investigated, less information is available about the effect of the linker on isoform selectivity. To this aim, in this work, we explored novel linker chemotypes to direct isoform selectivity. A small library of 25 hydroxamic acids with hitherto unexplored linker chemotypes was prepared. In vitro tests demonstrated that, depending on the linker type, some candidates selectively inhibit HDAC1 over HDAC6 isoform or vice versa. Docking calculations were performed to rationalize the effect of the novel linker chemotypes on biologic activity. Moreover, four compounds were able to increase the levels of acetylation of histone H3 or tubulin. These compounds were also assayed in breast cancer MCF7 cells to test their antiproliferative effect. Three compounds showed a significant reduction of cancer proliferation, representing valuable starting points for further optimization.
Polymer-assisted solution phase synthesis of the antihyperglycemic agent Rosiglitazone (Avandia).
Li, Xin,Abell, Chris,Warrington, Brian H,Ladlow, Mark
, p. 4392 - 4395 (2007/10/03)
The commercially important antihyperglycemic agent Rosiglitazone 1(Avandia) has been prepared in high purity by a multi-step, polymer-assisted solution phase (PASP) synthesis without the need for the conventional chromatographic purification of any intermediates.
