13618-49-0Relevant articles and documents
Synthesis of p-O-Alkyl Salicylanilide Derivatives as Novel EGFR Inhibitors
Zhang, Li,Hou, Lin,Sun, Wenyan,Yu, Zidong,Wang, Jibo,Gao, Hua,Yang, Guiming
, p. 37 - 42 (2016)
(Table Presented) Epidermal growth factor receptor (EGFR), a validated target for anticancer drugs, plays a critical role in tumorigenesis and tumor development. A series of p-O-alkyl salicylanilide derivatives were designed and synthesized as novel EGFR inhibitors using a salicylic acid scaffold. A simulated six-membered ring strategy formed through intramolecular hydrogen bonds was employed to mimic the planar quinazoline of the EGFR antagonist, gefitinib. The derived compounds with hydroxyl at the ortho position were more potent than ones with methoxyl group. In particular, compounds 5d and 5b displayed significant EGFR inhibitory (IC50 values = 0.30 and 0.45 μM, respectively) activity as well as potent antiproliferative activity in A431 and HCT-116 tumor cells. These salicylanilides could be considered as promising lead compounds for developing novel EGFR inhibitors.
Second-Generation Synthesis of the Northern Fragment of Mandelalide A: Role of π-Stacking on Sharpless Dihydroxylation of cis-Enynes
Ghosh, Ankan,Brueckner, Alexander C.,Cheong, Paul Ha-Yeon,Carter, Rich G.
, p. 9196 - 9214 (2019/08/12)
The development of a π-stacking-based approach for increased stereoselectivity in Sharpless asymmetric and diastereomeric dihydroxylation of cis-enynes is disclosed. The use of neighboring, electron-rich benzoate esters proved key to the success of this process. Density functional theory study suggests that the substrate benzoate ester group rigidifies the dihydroxylation transition states by forming a favorable π-stacking interaction in both Major-TS and Minor-TS. The energetic preference for the Major-TS was found in part because of the favorable eclipsing conformation of the alkene substituent as opposed to the disfavored bisecting conformation found in the Minor-TS. The application to a second-generation synthesis of the C15-C24 northern portion of mandelalide A is demonstrated.
Lipidated Brartemicin Analogues Are Potent Th1-Stimulating Vaccine Adjuvants
Foster, Amy J.,Nagata, Masahiro,Lu, Xiuyuan,Lynch, Amy T.,Omahdi, Zakaria,Ishikawa, Eri,Yamasaki, Sho,Timmer, Mattie S. M.,Stocker, Bridget L.
, p. 1045 - 1060 (2018/02/17)
Effective Th1-stimulating vaccine adjuvants typically activate antigen presenting cells (APCs) through pattern recognition receptors (PRRs). Macrophage inducible C-type lectin (Mincle) is a PRR expressed on APCs and has been identified as a target for Th1-stimulating adjuvants. Herein, we report on the synthesis and adjuvanticity of rationally designed brartemicin analogues containing long-chain lipids and demonstrate that they are potent Mincle agonists that activate APCs to produce inflammatory cytokines in a Mincle-dependent fashion. Mincle binding, however, does not directly correlate to a functional immune response. Mutation studies indicated that the aromatic residue of lead compound 9a has an important interaction with Mincle Arg183. In vivo assessment of 9a highlighted the capability of this analogue to augment the Th1 response to a model vaccine antigen. Taken together, our results show that lipophilic brartemicin analogues are potent Mincle agonists and that 9a has superior in vivo adjuvant activity compared to TDB.
