71205-21-5Relevant academic research and scientific papers
First synthesis of 3,6′- and 3,7′-biquinoline derivatives
Broch, Sidonie,Anizon, Fabrice,Moreau, Pascale
, p. 2039 - 2044 (2008)
The preparation of new 3,6′- and 3,7′-biquinoline derivatives was achieved by microwave-assisted Suzuki cross-coupling between N-protected 6- or 7-bromoquinolin-2(lH)-ones and quino-lin-3-ylboronic acid. Moreover, a new synthesis of 7-bromoquino-lin-2(lH)-one leading solely to the 7-substituted isomer was carried out. Thieme Stuttgart.
Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors
Huang, Shaei,Garbaccio, Robert M.,Fraley, Mark E.,Steen, Justin,Kreatsoulas, Constantine,Hartman, George,Stirdivant, Steve,Drakas, Bob,Rickert, Keith,Walsh, Eileen,Hamilton, Kelly,Buser, Carolyn A.,Hardwick, James,Mao, Xianzhi,Abrams, Marc,Beck, Steve,Tao, Weikang,Lobell, Rob,Sepp-Lorenzino, Laura,Yan, Youwei,Ikuta, Mari,Murphy, Joan Zugay,Sardana, Vinod,Munshi, Sanjeev,Kuo, Lawrence,Reilly, Michael,Mahan, Elizabeth
, p. 5907 - 5912 (2007/10/03)
Through a comparison of X-ray co-crystallographic data for 1 and 2 in the Chek1 active site, it was hypothesized that the affinity of the indolylquinolinone series (2) for Chek1 kinase would be improved via C6 substitution into the hydrophobic region I (HI) pocket. An efficient route to 6-bromo-3-indolyl-quinolinone (9) was developed, and this series was rapidly optimized for potency by modification at C6. A general trend was observed among these low nanomolar Chek1 inhibitors that compounds with multiple basic amines, or elevated polar surface area (PSA) exhibited poor cell potency. Minimization of these parameters (basic amines, PSA) resulted in Chek1 inhibitors with improved cell potency, and preliminary pharmacokinetic data are presented for several of these compounds.
