123864-93-7Relevant articles and documents
Conformational restriction design of thiophene-biphenyl-DAPY HIV-1 non-nucleoside reverse transcriptase inhibitors
Sang, Yali,Han,Pannecouque, Christophe,De Clercq, Erik,Zhuang, Chunlin,Chen
, (2019)
Conformational restriction is a promising strategy in the development of DAPY-type non-nucleoside reverse transcriptase inhibitors (NNRTIs). Herein, eighteen thiophene-biphenyl-DAPY derivatives were designed and synthesized as potent HIV-1 NNRTIs in which halogen and methyl groups were introduced to explore the conformationally constrained effects. Molecular docking and dynamic simulation analysis indicated that substituents on different positions of the biphenyl ring induced different dihedral angles and binding conformations, further explaining their anti-viral activities. The 2′-fluoro and 3′-chloro substitutions could form electrostatic or halogen-bonding interactions with adjacent residues of the RT enzyme. The 2′-methyl group contributed to enlarge the dihedral angle of biphenyl ring and was positioned to a space-filling hydrophobic pocket. Notably, compounds 22 and 23 with two methyl groups exhibited potent biological activity against WT HIV-1-infected MT-4 cells (EC50 = 14 and 17 nM, respectively) and RT enzyme (EC50 = 27 and 42 nM, respectively). In particular, 23 exhibited much lower cytotoxicity (CC50 = 264.19 μM) and higher selectivity index (SI = 18,564) than etravirine. Taken together, a rational conformational model for further design of DAPYs is proposed, providing a new guidance for the development of NNRTIs.
A Robust and Broadly Applicable Cobalt-Catalyzed Cross-Coupling of Functionalized Bench-Stable Organozinc Pivalates with Unsaturated Halides
Hammann, Jeffrey M.,Lutter, Ferdinand H.,Haas, Diana,Knochel, Paul
, p. 1082 - 1086 (2017/01/18)
We report a robust and broadly applicable CoCl2-catalyzed cross-coupling between functionalized aryl and heteroaryl zinc pivalates and various electron-poor aryl and heteroaryl halides (X=Cl, Br, I). Couplings with (E)- or (Z)-bromo- or iodo-alkenes proceed with retention of configuration. Also, alkynyl bromides react with arylzinc pivalates providing arylated alkynes.
Palladium nanoparticles on graphite oxide and its functionalized graphene derivatives as highly active catalysts for the Suzuki-Miyaura coupling reaction
Scheuermann, Gil M.,Steurer, Peter,Muelhaupt, Rolf,Rumi, Luigi,Bannwarth, Willi
supporting information; experimental part, p. 8262 - 8270 (2009/11/30)
Pd2+-exchanged graphite oxide and chemically derived graphenes therefrom were employed as supports for Pd nanoparticles. The influence of catalyst preparation, carbon functionalization, and catalyst morphology on the catalytic activity in the Suzuki-Miyaura coupling reactions was investigated. The catalysts were characterized by means of spectroscopy (FT-IR, solid-state 13C NMR, AAS, XPS), X-ray scattering (WAXS), surface area analysis (BET, methylene blue adsorption), and electron microscopy (TEM, ESEM). In contrast to the conventional Pd/C catalyst, graphite oxide and graphene-based catalysts gave much higher activities with turnover frequencies exceeding 39 000 h-1, accompanied by very low palladium leaching (1 ppm).
