1019780-59-6Relevant articles and documents
Copper-Catalyzed Enantioconvergent Cross-Coupling of Racemic Alkyl Bromides with Azole C(sp2)?H Bonds
Chang, Xiao-Yong,Chen, Ji-Jun,Gu, Qiang-Shuai,Jiang, Sheng-Peng,Li, Zhong-Liang,Liu, Lin,Liu, Xiao-Dong,Liu, Xin-Yuan,Su, Xiao-Long,Wang, Fu-Li,Yang, Chang-Jiang,Ye, Liu
supporting information, p. 380 - 384 (2020/10/30)
The development of enantioconvergent cross-coupling of racemic alkyl halides directly with heteroarene C(sp2)?H bonds has been impeded by the use of a base at elevated temperature that leads to racemization. We herein report a copper(I)/cinchona-alkaloid-derived N,N,P-ligand catalytic system that enables oxidative addition with racemic alkyl bromides under mild conditions. Thus, coupling with azole C(sp2)?H bonds has been achieved in high enantioselectivity, affording a number of potentially useful α-chiral alkylated azoles, such as 1,3,4-oxadiazoles, oxazoles, and benzo[d]oxazoles as well as 1,3,4-triazoles, for drug discovery. Mechanistic experiments indicated facile deprotonation of an azole C(sp2)?H bond and the involvement of alkyl radical species under the reaction conditions.
Synthesis, biological evaluation and molecular modelling studies of methyleneimidazole substituted biaryls as inhibitors of human 17α-hydroxylase-17,20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure
Jagusch, Carsten,Negri, Matthias,Hille, Ulrike E.,Hu, Qingzhong,Bartels, Marc,Jahn-Hoffmann, Kerstin,Mendieta, Mariano A.E. Pinto-Bazurco,Rodenwaldt, Barbara,Mueller-Vieira, Ursula,Schmidt, Dirk,Lauterbach, Thomas,Recanatini, Maurizio,Cavalli, Andrea,Hartmann, Rolf W.
, p. 1992 - 2010 (2008/09/20)
Novel chemical entities were prepared via Suzuki and SN reaction as AC-ring substrate mimetics of CYP17. The synthesised compounds 1-31 were tested for activity using human CYP17 expressed in Escherichia coli. Promising compounds were tested for selectivity against hepatic CYP enzymes (3A4, 2D6, 1A2, 2C9, 2C19, 2B6). Two potent inhibitors (27, IC50 = 373 nM/28, IC50 = 953 nM) were further examined in rats regarding their effects on plasma testosterone levels and their pharmacokinetic properties. Compound 28 was similarly active as abiraterone and showed better pharmacokinetic properties (higher bioavailability, t1/2 9.5 h vs 1.6 h). Docking studies revealed two new binding modes different from the one of the substrates and steroidal inhibitors.
