87707-51-5Relevant academic research and scientific papers
Design, Synthesis, and Biological Activity of New N -(Phenylmethyl)-benzoxazol-2-thiones as Macrophage Migration Inhibitory Factor (MIF) Antagonists: Efficacies in Experimental Pulmonary Hypertension
Le Hiress, Morane,Akagah, Bernardin,Bernadat, Guillaume,Tu, Ly,Thuillet, Rapha?l,Huertas, Alice,Phan, Carole,Fadel, Elie,Simonneau, Gérald,Humbert, Marc,Jalce, Ga?l,Guignabert, Christophe
, p. 2725 - 2736 (2018/04/23)
Macrophage migration inhibitory factor (MIF) is a key pleiotropic mediator and a promising therapeutic target in cancer as well as in several inflammatory and cardiovascular diseases including pulmonary arterial hypertension (PAH). Here, a novel series of N-(phenylmethyl)-benzoxazol-2-thiones 5-32 designed to target the MIF tautomerase active site was synthesized and evaluated for its effects on cell survival. Investigation of structure-activity relationship (SAR) particularly at the 5-position of the benzoxazole core led to the identification of 31 that potently inhibits cell survival in DU-145 prostate cancer cells and pulmonary endothelial cells derived from patients with idiopathic PAH (iPAH-ECs), two cell lines for which survival is MIF-dependent. Molecular docking studies helped to interpret initial SAR related to MIF tautomerase inhibition and propose preferred binding mode for 31 within the MIF tautomerase active site. Interestingly, daily treatment with 31 started 2 weeks after a subcutaneous monocrotaline injection regressed established pulmonary hypertension in rats.
Synthesis of 3-Substitued Benzoxazoline-2-thiones
Yamato, Masatoshi,Takeuchi, Yasuo,Hashigaki, Kuniko,Hattori, Kyoko,Muroga, Eiko,Hirota, Takashi
, p. 1733 - 1737 (2007/10/02)
Several methods for the preparation of 3-substitued benzoxazoline-2-hiones (1) were examined.Method B via the thiation of 3-substitued benzoxazoline-2-one (5) with phosphorus pentasulfide was found to be applicable to the preparation of most analogs of 1, with a few expections.Method C via the cyclization of 2-(alkylamino)phenol (7) with potassium O-methyldithiocarbonate was suitable for the preparation of analogs with a group sensitive to high temperature of with an aryl- (including aromatic heterocyclic ring) methyl group.In addition, the reaction of benzoxazoline-2-thione (2) with acetals such as 1-ethoxyisochroman, 2-ethoxytetrahydrofuran, and ethoxytetraydropyran, or with Michael acceptors such as 2,3-dihydrofuran and 2H-3,4-dihydropyran, gave 3-substitued benzoxazoline-2-thione (1d-f).
