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

Jung-Eun Park; Wan Keun Ji; Jae Wan Jang; Ae Nim Pae; Keehyun Choi; Ki Hang Choi; Jahyo Kang; Eun Joo Roh

doi:10.1016/j.bmcl.2012.12.072

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

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1887-90. doi: 10.1016/j.bmcl.2012.12.072. Epub 2013 Jan 12.

Authors

Jung-Eun Park¹, Wan Keun Ji, Jae Wan Jang, Ae Nim Pae, Keehyun Choi, Ki Hang Choi, Jahyo Kang, Eun Joo Roh

Affiliation

¹ Chemical Kinomics Research Center, Korea Institute of Science and Technology, Wolsong-gil 5, Seongbuk-gu, Seoul, Republic of Korea.

PMID: 23395659
DOI: 10.1016/j.bmcl.2012.12.072

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Calcium Channel Blockers / chemical synthesis*
Calcium Channel Blockers / chemistry
Calcium Channel Blockers / pharmacokinetics
Calcium Channels, T-Type / chemistry*
Calcium Channels, T-Type / metabolism
HEK293 Cells
Half-Life
Humans
Piperazine
Piperazines / chemical synthesis
Piperazines / chemistry*
Piperazines / pharmacokinetics
Rats
Stereoisomerism
Structure-Activity Relationship

Substances

Calcium Channel Blockers
Calcium Channels, T-Type
Piperazines
Piperazine