title: Synthesis and T-type calcium channel-blocking effects of aryl(1,5-disubstituted-pyrazol-3-yl)methyl sulfonamides for neuropathic pain treatment.
abstract: A novel series of aryl(1,5-disubstituted pyrazol-3-yl)methyl sulfonamide derivatives was designed, synthesized, and evaluated for T-type calcium channel (α1G and α1H) inhibitory activity. We identified several compounds, 9a, 9b, 9g, and 9h that displayed good T-type channel inhibitory potency with low hERG channel and CYP450 inhibition. Among them, 9a and 9b exhibited neuropathic pain alleviation effects in mechanical and cold allodynia induced in the SNL rat model. Compounds 9a and 9b displayed better efficacy than mibefradil and gabapentin against cold allodynia. In particular, compound 9a seemed to be valuable as shown fast acting performance in mechanical neuropathic pain model.
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institutes of Science and Technology (KIST), Seoul, 136-791, South Korea.
authors: Jung Hyun
authors: JH
authors: Kim
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institutes of Science and Technology (KIST), Seoul, 136-791, South Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), Gajungro 217, Youseong-gu, Daejeon, 305-350, South Korea.
authors: Gyochang
authors: G
authors: Keum
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institutes of Science and Technology (KIST), Seoul, 136-791, South Korea.
authors: Hesson
authors: H
authors: Chung
authors: Center for Neuro-Medicine, Brain Science Institute, Korea Institutes of Science and Technology (KIST), Seoul, 136-791, South Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), Gajungro 217, Youseong-gu, Daejeon, 305-350, South Korea. Electronic address: gsnam@kist.re.kr.
authors: Ghilsoo
authors: G
authors: Nam
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D060326:Chemistry Techniques, Synthetic; D004355:Drug Stability; D006801:Humans; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D013449:Sulfonamides
keywords: Allodynia; Aryl(1,5-disubstituted-pyrazol-3-yl)methyl sulfonamide; Neuropathic pain; T-type calcium channel inhibition