Synthesis and diabetic neuropathic pain-alleviating effects of 2N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1, 1-dioxide derivatives. Issue 17 (1st September 2017)

• Record Type: Journal Article
• Authors: Hong, Jin Ri; Choi, Young Jin; Keum, Gyochang; Nam, Ghilsoo
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 17(2017)
• Page Start: 4677
• Page End: 4685
• Publication Date: 2017-09-01
• Subjects: T-type calcium channel inhibition -- Fused-benzsulfonamides -- Neuropathic pain -- Allodynia; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.07.008
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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, and17, displayed potent T-type channel inhibitory activity. Among them, compounds10 and17 showed good metabolic stability in human liver microsomes, and low hERG channel and CYP450 inhibition. Compound10 exhibited diabetic neuropathic pain-alleviating effects in a streptozotocin-induced peripheral diabetic neuropathy (PDN) model. The maximum efficacy of compound10, which was 3-fold more potent than gabapentin, was observed at 1 h after administration, and co-administration of compound10 with gabapentin showed a considerable synergic effect.