7133-57-5Relevant academic research and scientific papers
Synthesis and biological evaluation of JL-A7 derivatives as potent ABCB1 inhibitors
Pan, Miaobo,Cui, Jian,Jiao, Lei,Ghaleb, Hesham,Liao, Chen,Zhou, Jiaqi,Kairuki, Mutta,Lin, Haiyan,Huang, Wenlong,Qian, Hai
, p. 4194 - 4202 (2017/07/05)
Cancer chemotherapy failure is often due to the overexpression of ATP-binding cassette (ABC) transporters (particularly ABCB1), resulting in a variety of structurally and pharmacologically unrelated drugs efflux. The multidrug resistance (MDR) phenomenon could be reversed by ABCB1 inhibitors. Now, JL-A7 as the lead compound based on a triazol-N-ethyl-tetrahydroisoquinoline scaffold, 18 compounds were designed and synthesized. Substitution in para positions yielded high activities toward ABCB1. Moreover, compound 5 could effectively block the drug efflux function of ABCB1 and increase the accumulation of anti-cancer drugs to achieve effective treatment concentration in MDR cells.
6,7-Dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinolines as superior reversal agents for P-glycoprotein-mediated multidrug resistance
Liu, Baomin,Qiu, Qianqian,Zhao, Tianxiao,Jiao, Lei,Li, Yunman,Huang, Wenlong,Qian, Hai
, p. 336 - 344 (2015/02/05)
P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy. Based on our previous study, 17 novel compounds with the 6,7-dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinoline scaffold were designed and synthesized. Among them, 2-[(1-{4-[2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl]phenyl}-1H-1,2,3-triazol-4-yl)methoxy]-N-(p-tolyl)-benzamide (compound 7h) was identified as a potent modulator of P-gp-mediated MDR, with high potency (EC50 = 127.5 ± 9.1 nM), low cytotoxicity (TI > 784.3), and long duration (> 24 h) in reversing doxorubicin (DOX) resistance in K562/A02 cells. Compound 7h also enhanced the effects of other MDR-related cytotoxic agents (paclitaxel, vinblastine, and daunorubicin), increased the accumulation of DOX and blocked P-gp-mediated rhodamine 123 efflux function in K562/A02 MDR cells. Moreover, 7h did not have any effect on cytochrome (CYP3A4) activity. These results indicate that 7h is a relatively safe modulator of P-gp-mediated MDR that has good potential for further development.
Anion-triggered substituent-dependent conformational switching of salicylanilides. New hints for understanding the inhibitory mechanism of salicylanilides
Guo, Lin,Wang, Qiang-Li,Jiang, Qian-Qian,Jiang, Qiu-Ju,Jiang, Yun-Bao
, p. 9947 - 9953 (2008/09/17)
(Chemical Equation Presented) A series of salicylanilides (1a-h) bearing varied substituents at the 3′- or 4′-position of the anilino moiety (substituent = p-OCH3, p-CH3, m-CH3, H, p-Cl, m-Cl, p-CO2CH3, and p-CN) were synthesized. In acetonitrile all of the substituted salicylanilides 1a-h predominantly adopt the "closed-ring" conformation facilitated by a strong intramolecular OH...O=C hydrogen bond. In the presence of H2PO4 -, the conformation of 1a-h was found to be modulated by the substituent. With our proposed proton-transfer fluorescence probing method, we were able to show that the conformation of 1a-f bearing a not highly electron-withdrawing substituent was switched to the "open-ring" form by H2PO4-, whereas 1h bearing a highly electron-withdrawing substituent, p-CN, remained in the "closed-ring" conformation. The significance of these findings for understanding, from a molecular structural point of view, the mechanism of salicylanilide-based inhibitors for inhibiting the protein tyrosine kinase epidermal growth factor receptor was discussed.
4-Acylhydrazinomethylene-2-phenyloxazol-5(4H)-ones as acylating agents: Synthesis of salicylanilides and 1,2,4-triazolo[4,3-b] pyridazines
Po?gan, Franc,Polanc, Slovenko,Ko?evar, Marijan
, p. 1011 - 1019 (2007/10/03)
A simple and general method for the acylation of an amino or hydrazino group by the application of hydrazides has been developed. It starts from hydrazides (2), which are converted with 4-ethoxymethylene-2-phenyl-oxazol-5(4H)-one (1) to the corresponding 4-acylhydrazinomethylene-2-phenyloxazol-5(4H)-ones (3). The latter react with nitrogen-containing nucleophiles in 1,4-dioxane in the presence of triethylamine or zirconium(IV) chloride to give the corresponding amides (7) or mixtures of hydrazides (12) and 1,2,4-triazolo[4,3-b]pyridazines (11). Upon prolonged heating, compounds (11) are the main products.
PHOTOCHEMICAL AND THERMAL REACTIONS OF 2-ARYLOXYBENZOHYDROXAMIC ACIDS
Hosangadi, B. D.,Nimbalkar, M. M.,Patel, N. R.
, p. 5857 - 5860 (2007/10/02)
2-Aryloxybenzohydroxamic acids 1-7 were subjected to photolysis in benzene or methanol.In each case corresponding N-arylsalicylamides 8-10 were obtained in good yields.Compounds 1-7 on thermolysis in decaline also produced 8-10.
