Microwave-Assisted Solid-Phase Synthesis of a 1,2-Disubstituted Benzimidazole Library by Using a Phosphonium Linker

Asymmetric Total Synthesis and Evaluation of Antitumor Activity of Ophiorrhisine A and Its Derivatives

“…Nitration of 20, reduction of aldehyde, and bromination by the Appel reaction yielded bromide 21, 9 which was subjected to the Finkelstein reaction to give iodide 22. 10 Stereoselective alkylation of bromide 21 or iodide 22 with Schollkopf reagent 11 in the presence of copper cyanide 12 afforded alkylated compound 23 as a single diastereomer. Cleavage of the chiral auxiliary in 23 with dilute aqueous HCl in MeCN gave chiral phenylalanine derivative 8, 13 which was then coupled with N-Boc-L-phenylalanine (7) to afford dipeptide 24.…”

“…Data are consistent with literature values. 10 Alkylated Compound 23. CuCN (423.2 mg, 1.5 equiv) was added into a vial equipped with a stirrer bar and dried well over 1 h under reduced pressure.…”

Identification of 2-(4-N,N-Dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole targeting HIV-1 CA capsid protein and inhibiting HIV-1 replication in cellulo

“…Then, based on the compound which showed an inhibitory effect in our assembly assay, we extended our selection with additional molecules related to these lead compounds to finally consider 22 molecules in total for their inhibitory effect on HIV-1 replication in U87 cells. The chemical synthesis of these molecules followed the previously reported procedures [ 28 , 30 , 33 , 38 , 39 ]. Synthesis and in-depth characterization of the two compounds 696 [ 27 ] and 314, which are thoroughly analyzed in this study, are available as supporting information.…”

“…More than 400 compounds from our chemical library described elsewhere [28][29][30] have been tested for their ability to interfere with CA assembly. As the assembly inhibition assay requires high protein and molecule concentrations, with the concomitant solubility problems, a dose-response curve could not be determined for this assay as the 1:1 protein: compound ratio is unreachable.…”

“…More than 400 compounds from our chemical library described elsewhere have been tested for their ability to interfere with CA assembly. Then from the data previously acquired from those 400 molecules tested in CA from FIV, we selected 10 compounds for their structural relationship with known CA HIV-1 inhibitors [27][28][29][30][31]. From those molecules, 5 compounds demonstrated interference with the assembly of HIV-1 CA in vitro One hit molecule, compound 696, which was recently shown by NMR to bind FIV capsid protein [27], demonstrated an inhibitory effect on HIV-1 replication in cellulo, with an IC 50 of 3 µM.…”