Preparation and Pharmacological Evaluation of New Pyrazole and Isoxazole Derivatives for the Treatment of Neuropathic Pain

Title
Preparation and Pharmacological Evaluation of New Pyrazole and Isoxazole Derivatives for the Treatment of Neuropathic Pain
Authors
이주현강순방정낙철금교창
Issue Date
2011-09
Publisher
대한화학회 추계 학술대회
Citation
VOL 108, P-319
Abstract
Neuropathic pain is a debilitating chronic syndrome that often arises from injuries to central and peripheral nerves. Such pain has been hypothesized to be the result of an aberrant expression and function of calcium channels at the site of injury.In particular, the expression and modulation of the T-type calcium channel plays a key role in the pathogenesis of neuropathic pain, and blocking this channel is well known to be therapeutically important.Neuropathic pain is the focus of much current research activity, particularly pharmacological research. Hence, we have attempted to study on the development of new drug active on T-type Ca2+ channel with good selectivity as a neuropathic pain therapy. A series of novel pyrazole and isoxazole derivatives were designed and synthesized based on the 3D pharmacophore model derived from known T-type Ca2+channel blockers. Synthesized compounds were evaluated invitro inhibitory activities with α1G and α1H T-type Ca2+ channel in FDSS assay system, and tested the selectivity against hERG channel, N-type, and L-type Ca2+channel. Some compounds having good Ttype calcium channel activity possessed good CYP profile and plasma and microsomal stability and good PK profile. Among them, 3c compound demonstrated diminished neuropathic pain at the in-vivo pain animal model. Furthermore, the structure-activity relationship of these series will be discussed.
URI
http://pubs.kist.re.kr/handle/201004/42768
Appears in Collections:
KIST Publication > Conference Paper
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