51814-55-2Relevant articles and documents
Efficient and accessible silane-mediated direct amide coupling of carboxylic acids and amines
D'Amaral, Melissa C.,Jamkhou, Nick,Adler, Marc J.
supporting information, p. 288 - 295 (2021/01/28)
A straightforward method for the direct synthesis of amides from amines and carboxylic acids without exclusion of air or moisture using diphenylsilane with N-methylpyrrolidine has been developed. Various amides are made efficiently, and broad functional group compatibility is shown through a Glorius robustness study. A gram-scale synthesis demonstrates the scalability of this method. This journal is
Cytotoxic activity of synthetic chiral amino acid derivatives
de Castro, Pedro P.,Siqueira, Raoni P.,Conforte, Luiza,Franco, Chris H.J.,Bressan, Gustavo C.,Amarante, Giovanni W.
, p. 193 - 200 (2019/12/28)
Cancer is a chronic degenerative disease considered one of the most important causes of death worldwide. In this context, a series of dual-protected amino acid derivatives was synthesized and evaluated as potential novel anticancer agents. The 40 derivatives were prepared in up to three reaction steps. The cytotoxic activities were screened in vitro against a panel of tumor and non-tumor cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among the synthesized derivatives, three of them showed promising activity against cancer cells with half-maximal inhibitory concentration (IC50) ranging between 1.7-6.1 μM. The most promising derivative, bearing both a lipophilic N-alkyl diamine moiety and a protected amino acid scaffold showed a selectivity index of 3.4 towards tumor cells. The N-alkyl diamine moiety seems to play a crucial role in the enhancement of the anticancer activity. On the other hand, the incorporation of an amino acid scaffold resulted in increase in the selectivity towards cancer cell lines.
An inhibitor of fatty acid synthase thioesterase domain with improved cytotoxicity against breast cancer cells and stability in plasma
Lupien, Leslie E.,Dunkley, Evan M.,Maloy, Margaret J.,Lehner, Ian B.,Foisey, Maxwell G.,Ouellette, Maddison E.,Lewis, Lionel D.,Pooler, Darcy Bates,Kinlaw, William B.,Baures, Paul W.
supporting information, p. 171 - 185 (2019/11/02)
It is well recognized that many cancers are addicted to a constant supply of fatty acids (FAs) and exhibit brisk de novo FA synthesis. Upregulation of a key lipogenic enzyme, fatty acid synthase (FASN), is a near-universal feature of human cancers and their precursor lesions, and has been associated with chemoresistance, tumor metastasis, and diminished patient survival. FASN inhibition has been shown to be effective in killing cancer cells, but progress in the field has been hindered by off-target effects and poor pharmaceutical properties of candidate compounds. Our initial hit (compound 1) was identified from a high-throughput screening effort by the Sanford-Burnham Center for Chemical Genomics using purified FASN thioesterase (FASN-TE) domain. Despite being a potent inhibitor of purified FASN-TE, compound 1 proved highly unstable in mouse plasma and only weakly cytotoxic to breast cancer (BC) cells in vitro. An iterative process of synthesis, cytotoxicity testing, and plasma stability assessment was used to identify a new lead (compound 41). This lead is more cytotoxic against multiple BC cell lines than tetrahydro-4-methylene-2S-octyl-5-oxo-3R-furancarboxylic acid (the literature standard for inhibiting FASN), is stable in mouse plasma, and shows negligible cytotoxic effects against nontumorigenic mammary epithelial cells. Compound 41 also has drug-like physical properties based on Lipinski’s rules and is, therefore, a valuable new lead for targeting fatty acid synthesis to exploit the requirement of tumor cells for fatty acids.
