182223-59-2Relevant articles and documents
Lead Discovery of Dual G-Quadruplex Stabilizers and Poly(ADP-ribose) Polymerases (PARPs) Inhibitors: A New Avenue in Anticancer Treatment
Salvati, Erica,Botta, Lorenzo,Amato, Jussara,Di Leva, Francesco Saverio,Zizza, Pasquale,Gioiello, Antimo,Pagano, Bruno,Graziani, Grazia E.,Tarsounas, Madalena,Randazzo, Antonio,Novellino, Ettore,Biroccio, Annamaria,Cosconati, Sandro
, p. 3626 - 3635 (2017)
G-quadruplex stabilizers are an established opportunity in anticancer chemotherapy. To circumvent the antiproliferative effects of G4 ligands, cancer cells recruit PARP enzymes at telomeres. Herein, starting from the structural similarity of a potent G4 ligand previously discovered by our group and a congeneric PARP inhibitor, a library of derivatives was synthesized to discover the first dual G4/PARP ligand. We demonstrate that a properly decorated thieno[3,2-c]quinolin-4(5H)-one stabilizes the G4 fold in vitro and in cells, induces a DNA damage response localized to telomeres, inhibits PARylation in cells, and has an antiproliferative effect in BRCA2 deficient tumor cells.
CCR3 antagonists: a potential new therapy for the treatment of asthma. Discovery and structure-activity relationships.
Wacker, Dean A,Santella 3rd., Joseph B,Gardner, Daniel S,Varnes, Jeffrey G,Estrella, Melissa,DeLucca, George V,Ko, Soo S,Tanabe, Keiichi,Watson, Paul S,Welch, Patricia K,Covington, Maryanne,Stowell, Nicole C,Wadman, Eric A,Davies, Paul,Solomon, Kimberly A,Newton, Robert C,Trainor, George L,Friedman, Steven M,Decicco, Carl P,Duncia, John V
, p. 1785 - 1789 (2007/10/03)
CCR3 antagonist leads with IC(50) values in the microM range were converted into low nM binding compounds that displayed in vitro inhibition of human eosinophil chemotaxis induced by human eotaxin. In particular, 4-benzylpiperidin-1-yl-n-propylureas and erythro-3-(4-benzyl-2-(alpha-hydroxyalkyl)piperidin-1-yl)-n-propylureas (obtained via Beak reaction of N-BOC-4-benzylpiperidine) exhibited single digit nanomolar IC(50) values for CCR3.
