ABSTRACT
Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,
ABSTRACT
AIM To synthesize piperazine derivatives and screen anti-tumor compounds with higher activity and lower toxicity. METHODS Selecting 1,4-bis(3-bromopropionyl)piperazine as leading compound, a series of 1,4-bis［3-(amino-dithiocarboxy)propionyl］ piperazine derivatives (4a-j) were synthesized through the use of aminodithiocarboxylate. All the synthetic compounds (4a-j) were tested for their anti-tumor activity against eight kinds of tumor cells. RESULTS Compounds (4a-j) are new compounds, among them, compounds 4c, 4d and 4e showed anti-tumor activity against HL-60. The inhibition of compounds 4c, 4d and 4e against HL-60 are 44%, 90% and 70% respectively, at the concentration of 10 μmol.L-1. However, the inhibition of the other kinds of anti-tumor cells are not distinctive. CONCLUSION These results suggest that this may be one of the effective routes to improve the anti-tumor activity and reduce the toxicity of 1,4-bis(3-bromopropionyl)piperazine.
ABSTRACT
AIM To investigate the analgesic effect of 1,6 Di (4 phenethyl 1 methyl 1 piperazinyl) hexane dibromide (97 9 G4) and its mechanisms. METHODS The writhing model of mice induced by acetic acid, hot plate test (sc, icv), tail flick test and the model of electrical stimulation induced contraction of guinea pig ileum were used. RESULTS The inhibition of writhing reaction induced by acetic acid was found (ID 50 =8 8 mg?kg -1 ) and the rising of mice pain threshold in hot plate test and in tail flick test was obvious ( P