Synthesis and biological evaluation of 1-(2-hydroxy-3-phenyloxypropyl)piperazine derivatives as T-type calcium channel blockers

To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3-phenoxypropyl piperazine derivatives were synthesized and evaluated for in vitro activities. Compound 6m and 6q showed high selectivity over hERG channel (IC50 ratio of hERG/α1G6m=8.5, 6q=18....

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2013-03, Vol.23 (6), p.1887-1890
Main Authors: Park, Jung-eun, Ji, Wan Keun, Jang, Jae Wan, Pae, Ae Nim, Choi, Keehyun, Choi, Ki Hang, Kang, Jahyo, Roh, Eun Joo
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
calcium channel blockers
Calcium Channel Blockers - chemical synthesis
Calcium Channel Blockers - chemistry
Calcium Channel Blockers - pharmacokinetics
calcium channels
Calcium Channels, T-Type - chemistry
Calcium Channels, T-Type - metabolism
chemistry
Half-Life
HEK293 Cells
Humans
inhibitory concentration 50
pharmacokinetics
piperazine
Piperazines - chemical synthesis
Piperazines - chemistry
Piperazines - pharmacokinetics
Rats
Stereoisomerism
Structure-Activity Relationship
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Summary:To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 2-hydroxy-3-phenoxypropyl piperazine derivatives were synthesized and evaluated for in vitro activities. Compound 6m and 6q showed high selectivity over hERG channel (IC50 ratio of hERG/α1G6m=8.5, 6q=18.38) and they were subjected to measure pharmacokinetics profiles. Among them compound 6m showed an excellent pharmacokinetic profile in rats.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2012.12.072