144291-47-4Relevant articles and documents
Poly(ethylene glycol) supported liquid phase synthesis of biaryls
Blettner, Carsten G.,K?nig, Wilfried A.,Stenzel, Wolfgang,Schotten, Theo
, p. 295 - 297 (1998)
The liquid phase synthesis of biaiyls via Suzuki cross-coupling reaction on polyethylene glycol) supports (PEGs) is described. The reaction is exemplified by parallel coupling of polymer bound aryl halides with boronic acids. Four different PEGs were employed as soluble polymer supports for parallel synthesis. The generated libraries include both sterically hindered aryl halides (2b, 2d) and boronic acids. The reactions were run in the homogeneous phase and the synthetic sequences performed in parallel fashion. Quantitative conversion in the Suzuki couplings was verified by 1H-NMR analysis (3a-r). The polymer bound products were isolated in good to excellent (52% to 98%) yields by either simple precipitation of the soluble support or column filtration.
Discovery of ONO-7300243 from a Novel Class of Lysophosphatidic Acid Receptor 1 Antagonists: From Hit to Lead
Terakado, Masahiko,Suzuki, Hidehiro,Hashimura, Kazuya,Tanaka, Motoyuki,Ueda, Hideyuki,Kohno, Hiroshi,Fujimoto, Taku,Saga, Hiroshi,Nakade, Shinji,Habashita, Hiromu,Takaoka, Yoshikazu,Seko, Takuya
supporting information, p. 913 - 918 (2016/10/22)
Lysophosphatidic acid (LPA) evokes various physiological responses through a series of G protein-coupled receptors known as LPA1-6. A high throughput screen against LPA1 gave compound 7a as a hit. The subsequent optimization of 7a led to ONO-7300243 (17a) as a novel, potent LPA1 antagonist, which showed good efficacy in vivo. The oral dosing of 17a at 30 mg/kg led to reduced intraurethral pressure in rats. Notably, this compound was equal in potency to the α1 adrenoceptor antagonist tamsulosin, which is used in clinical practice to treat dysuria with benign prostatic hyperplasia (BPH). In contrast to tamsulosin, compound 17a had no impact on the mean blood pressure at this dose. These results suggest that LPA1 antagonists could be used to treat BPH without affecting the blood pressure. Herein, we report the hit-to-lead optimization of a unique series of LPA1 antagonists and their in vivo efficacy.
General and practical carboxyl-group-directed remote C-H oxygenation reactions of arenes
Wang, Yang,Gulevich, Anton V.,Gevorgyan, Vladimir
supporting information, p. 15836 - 15840 (2014/04/03)
Two methods for remote aromatic C-H oxygenation reactions, have been developed. Method1, the Cu-catalyzed oxygenation reaction, is highly efficient for cyclization of electron-neutral and electron-rich biaryl carboxylic acids into 3,4-benzocoumarins. Method2, the K2S2O 8-mediated oxygenation reaction, is more general and practical for cyclization of substrates with electron-donating and -withdrawing groups (see scheme). Copyright