Design and synthesis of new RAF kinase-inhibiting antiproliferative quinoline derivatives. Part 2: Diarylurea derivatives.

This article describes the design, synthesis, and biological screening of a new series of diarylurea derivatives possessing quinoline nucleus. Nine target compounds were selected by the National Cancer Institute (NCI, Bethesda, Maryland, USA) for in vitro antiproliferative screening against a panel of 58 cancer cell lines of nine cancer types. Following one-dose initial screening, compounds 1d-g and 2b were selected for 5-dose screening in order to calculate their IC and total growth inhibition (TGI) values against the cell lines.

Design and synthesis of a new series of highly potent RAF kinase-inhibiting triarylpyrazole derivatives possessing antiproliferative activity against melanoma cells.

Background: Inhibition of V600E-B-RAF kinase represents a potential avenue for melanoma treatment. Herein, a series of 1,3,4-triarylpyrazoles possessing amide linker were designed, synthesized and evaluated for RAF kinase inhibition.

Results: Compounds 1d and 1f were more potent than sorafenib against A375 cell line, and their selectivity indexes toward A375 than HS27 fibroblasts were 25.

A Progressive Review of V600E-B-RAF-Dependent Melanoma and Drugs Inhibiting It.

B-RAF gene is a component of the MAPK pathway that plays a very important role in cell division, survival, proliferation, and many other cellular functions. Mutations of the B-RAF (such as V600E-B-RAF) lead to melanoma, which is one of the leading causes of death worldwide. R&D progress is being done aiming at improved therapy in the future.

A new series of diarylamides possessing quinoline nucleus: Synthesis, in vitro anticancer activities, and kinase inhibitory effect.

Synthesis of a new series of diarylamides possessing 6,7-dimethoxy(dihydroxy)quinoline scaffold is described. Their in vitro antiproliferative activities against NCI-58 human cancer cell lines of nine different cancer types were tested. Compounds 1a and 1d-g showed the highest mean %inhibition values over the 58 cell line panel at 10 μM, and they were further tested in 5-dose testing mode to determine their IC50 values.

Transition-metal/Lewis acid free synthesis of acyl benzothiophenes via C-C bond forming reaction.

A simple and single-step synthesis of 2- and 3-acyl substituted benzothiophenes has been described via environmentally benign acylation of benzothiophene with in situ generated acyl trifluoroacetates. Both aliphatic and aromatic carboxylic acids participated in trifluoroacetic anhydride/phosphoric acid mediated C-C bond forming reactions under solvent-free conditions affording acyl benzothiophenes in good overall yields.