147621-19-0Relevant articles and documents
Identification of an Indazole-Based Pharmacophore for the Inhibition of FGFR Kinases Using Fragment-Led de Novo Design
Turner, Lewis D.,Summers, Abbey J.,Johnson, Laura O.,Knowles, Margaret A.,Fishwick, Colin W. G.
supporting information, p. 1264 - 1268 (2017/12/26)
Structure-based drug design (SBDD) has become a powerful tool utilized by medicinal chemists to rationally guide the drug discovery process. Herein, we describe the use of SPROUT, a de novo-based program, to identify an indazole-based pharmacophore for the inhibition of fibroblast growth factor receptor (FGFR) kinases, which are validated targets for cancer therapy. Hit identification using SPROUT yielded 6-phenylindole as a small fragment predicted to bind to FGFR1. With the aid of docking models, several modifications to the indole were made to optimize the fragment to an indazole-containing pharmacophore, leading to a library of compounds containing 23 derivatives. Biological evaluation revealed that these indazole-containing fragments inhibited FGFR1-3 in the range of 0.8-90 μM with excellent ligand efficiencies of 0.30-0.48. Some compounds exhibited moderate selectivity toward individual FGFRs, indicating that further optimization using SBDD may lead to potent and selective inhibitors of the FGFR family.
Scope of the suzuki-Miyaura cross-coupling reactions of potassium heteroaryltrifluoroborates
Molander, Gary A.,Canturk, Belgin,Kennedy, Lauren E.
supporting information; experimental part, p. 973 - 980 (2009/07/11)
A wide variety of bench-stable potassium heteroaryltrifluoroborates were prepared, and general reaction conditions were developed for their cross-coupling to aryl and heteroaryl halides. The cross-coupled products were obtained in good to excellent yields. This method represents an efficient and facile installation of heterocyclic building blocks onto preexisting organic substructures.
3-(2-(3-Pyridinyl)thiazolidin-4-oyl)indoles, a Novel Series of Platelet Activating Factor Antagonists
Sheppard, George S.,Pireh, Daisy,Carrera, George M.,Bures, Mark G.,Heyman, H. Robin,et al.
, p. 2011 - 2032 (2007/10/02)
(2RS,4R)-3-(2-(3-pyridinyl)thiazolidin-4-oyl)indoles represent a new class of potent, orally active antagonists of platelet activating factor (PAF). The compounds were prepared by acylation of the magnesium or zinc salts of substituted indoles with (2RS,4R)-2-(3-pyridinyl)-3-(tert-butoxycarbonyl)thiazolidin-4-oyl chloride. The 3-acylindole moiety functions as a hydrolytically stabilized and conformationally restricted anilide replacement, which imparts a considerable boost in potency to the series. Structure-activity relationships observed for substitution on the indole ring system are discussed. Members of the series compare favorably with other reported PAF antagonists.