Hong, Jin Ri Choi, Young Jin Keum, Gyochang Nam, Ghilsoo 2024-01-20T00:33:11Z 2024-01-20T00:33:11Z 2021-09-05 2017-09-01 0968-0896 https://pubs.kist.re.kr/handle/201004/122305 A novel series of fused-benzensulfonamide 2-N-(pyrazol-3-yl)methylbenzoldlisothiazole-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 co administration of compound 10 with gabapentin showed a considerable synergic effect. (C) 2017 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD T-TYPE CALCIUM-CHANNELS SENSORY NEURONS MODELS Synthesis and diabetic neuropathic pain-alleviating effects of 2N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives Article 10.1016/j.bmc.2017.07.008 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.25, no.17, pp.4677 - 4685 BIOORGANIC & MEDICINAL CHEMISTRY 25 17 4677 4685 scie scopus 000407831300014 2-s2.0-85023645219 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article T-TYPE CALCIUM-CHANNELS SENSORY NEURONS MODELS T-type calcium channel inhibition Fused-benzsulfonamides Neuropathic pain Allodynia