Synthesis and diabetic neuropathic pain-alleviating effects of 2N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives

Title
Synthesis and diabetic neuropathic pain-alleviating effects of 2N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives
Authors
남길수금교창최영진홍진리
Keywords
Fused-benzsulfonamides; T-type calcium channel inhibition; Allodynia; Neuropathic pain
Issue Date
2017-09
Publisher
Bioorganic & medicinal chemistry
Citation
VOL 25-4685
Abstract
A novel series of fused-benzensulfonamide 2-N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives was designed and synthesized as metabolically stable T-type calcium channel inhibitors. Several compounds, 9, 10, and 17, displayed potent T-type channel inhibitory activity. Among them, compounds 10 and 17 showed good metabolic stability in human liver microsomes, and low hERG channel and CYP450 inhibition. Compound 10 exhibited diabetic neuropathic pain-alleviating effects in a streptozotocin-induced peripheral diabetic neuropathy (PDN) model. The maximum efficacy of compound 10, which was 3-fold more potent than gabapentin, was observed at 1 h after administration, and coadministration of compound 10 with gabapentin showed a considerable synergic effect.
URI
http://pubs.kist.re.kr/handle/201004/66141
ISSN
0968-0896
Appears in Collections:
KIST Publication > Article
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