82394-01-2Relevant academic research and scientific papers
New Triazine Derivatives as Potent Modulators of Multidrug Resistance
Dhainaut, Alain,Regnier, Gilbert,Atassi, Ghanem,Pierre, Alain,Leonce, Stephane,et al.
, p. 2481 - 2496 (2007/10/02)
A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity.Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5μM in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin.The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators.In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the T/C by 39percent in mice bearing the resistant tumor cell line P388/VCR.According to these interesting properties, 16 was selected for a clinical development because it is more bioavailable than 34, even though it was less active.
N-SUBSTITUTED DERIVATIVES OF 6,11-DIHYDRODIBENZOTHIEPIN-11-AMINE AND RELATED COMPOUNDS; SYNTHESIS AND PHARMACOLOGICAL SCREENING
Valenta, Vladimir,Hulinska, Hana,Holubek, Jiri,Dlabac, Antonin,Metys, Jan,et al.
, p. 860 - 869 (2007/10/02)
Reactions of N-(6,11-dihydrodibenzothiepin-11-yl)chloroacetamide (II) with dimethylamine, morpholine, and 2-(1-piperazinyl)ethanol afforded the amino amides III-V.Substitution reactions of 11-chloro-6,11-dihydrodibenzothiepin with ethylenediamine and N,N-dimethylethylenediamine gave the diamines VI and VII. 6,11-Dihydrodibenzothiepin-11-amine (I) was treated with ethyl chloroacetate and ethyl 2-bromopropionate to give the amino esters X and XI which were transformed on the one hand to the acids VIII and IX, and to the amides XII and XIII on the other.(6,11-Dihydrodibenzothiepin-11-yl)methylamine (XVIa) and (10,11-dihydro-5H-dibenzocycloheptene-5-yl)methylamine (XVIb) were transformed via the chloroacetamides XVIIa and XVIIb to the (4-methyl-1-piperazinyl)acetamides XVa and XVb.Compound V showed local anaesthetic and antiarrhytmic activity, the diamine VII had antihistamine and antireserpine effects, the amide XII was found to be an anticonvulsant, and the piperazines XVa and XVb inhibited effectively the formation of the indomethacin-induced gastric ulcers in rats.
