An Exhaustive Compilation on the Synthesis of Heterocycles Pendant on the Fatty Acid Alkyl Chains.

Fatty acids derived from oils and fats of different plant and animal resources are considered one of the most valuable renewable precursors of the synthetic chemical and pharmaceutical industries. On the other hand, heterocyclic compounds are well known nowadays by their constitution of many commercialized drugs due to their unique biological activities. Combination between fatty acids and heterocyclic compounds has made important advances in the construction of valuable biologically relevant molecules in pharmaceutical industry. This review casts light on the synthetic pathways for construction of the fatty acid-heterocycle hybrid up to date in a simple classification and arranged manner.

Novel thiazole derivatives incorporating phenyl sulphonyl moiety as potent BRAFV600E kinase inhibitors targeting melanoma.

Novel thiazole derivatives possessing phenyl sulfonyl moiety were designed and synthesized as B-RAFV600E kinase inhibitors based on the clinically-approved anticancer drug, dabrafenib. All target compounds showed significant inhibition of B-RAFV600E kinase enzyme at nanomolar levels. Compounds 7b and 13a revealed excellent B-RAFV600E inhibitory activity, superior to that of dabrafenib with IC50 values of 36.3 ± 1.9, 23.1 ± 1.2, and 47.2 ± 2.5 nM, respectively. Moreover, the title compounds were much more selective toward B-RAFV600E kinase than B-RAF wild type. In addition, the most potent compounds were further evaluated for their anticancer activity against B-RAFV600E-mutated and wild type melanoma cells. A positive correlation between the cytotoxic activity and selectivity for B-RAF V600E over B-RAF wild type was clearly observed for compounds 7b, 11c, 13a, and 17. All the screened compounds potently inhibited the growth of WM266.4 melanoma cells with IC50 values in the range from 1.24 to 17.1 µM relative to dabrafenib (IC50 = 16.5 ± 0.91 µM). Compounds 7b, 11a and 11c, 13a, and 17 were much more potent than dabrafenib against B-RAFV600E-mutated WM266.4 melanoma cells. Furthermore, compound 7b suppressed the phosphorylation of downstream ERK1/2 from WM266.4 cells. Also, the docking study revealed the proper orientation and well-fitting of the title compounds into the ATP binding site of B-RAFV600E kinase.

Pyrimidyl formamidine palladium(II) complex as a nanocatalyst for aqueous Suzuki-Miyaura coupling.

Synthesis of a new phosphene-free nano-size formamidine-based palladium complex have been achieved. The molecular structure of novel palladium complex have been confirmed using spectroscopic methods of analysis as well as physical characterizations. The synthesized complex has been used as a catalyst for microwave assisted aqueous Suzuki-Miyaura Cross-coupling (SMC) of aryl bromides with phenylboronic acid. The formamidine-based Pd(II)-complex exhibited excellent catalytic activity to obtain biaryls using mild reaction conditions.