1450596-57-2Relevant academic research and scientific papers
Discovery of DS-1971a, a Potent, Selective NaV1.7 Inhibitor
Shinozuka, Tsuyoshi,Kobayashi, Hiroyuki,Suzuki, Sayaka,Tanaka, Kyosuke,Karanjule, Narayan,Hayashi, Noriyuki,Tsuda, Toshifumi,Tokumaru, Eri,Inoue, Masahiro,Ueda, Kiyono,Kimoto, Hiroko,Domon, Yuki,Takahashi, Sakiko,Kubota, Kazufumi,Yokoyama, Tomihisa,Shimizugawa, Akiko,Koishi, Ryuta,Fujiwara, Chie,Asano, Daigo,Sakakura, Tomoko,Takasuna, Kiyoshi,Abe, Yasuyuki,Watanabe, Toshiyuki,Kitano, Yutaka
, p. 10204 - 10220 (2020/11/02)
A highly potent, selective NaV1.7 inhibitor, DS-1971a, has been discovered. Exploration of the left-hand phenyl ring of sulfonamide derivatives (I and II) led to the discovery of novel series of cycloalkane derivatives with high NaV1.7 inhibitory potency in vitro. As the right-hand heteroaromatic ring affected the mechanism-based inhibition liability of CYP3A4, replacement of this moiety resulted in the generation of 4-pyrimidyl derivatives. Additionally, GSH adducts formation, which can cause idiosyncratic drug toxicity, was successfully avoided by this modification. An additional optimization led to the discovery of DS-1971a. In preclinical studies, DS-1971a demonstrated highly potent selective in vitro profile with robust efficacy in vivo. DS-1971a exhibited a favorable toxicological profile, which enabled multiple-dose studies of up to 600 mg bid or 400 mg tid (1200 mg/day) administered for 14 days to healthy human males. DS-1971a is expected to exert potent efficacy in patients with peripheral neuropathic pain, with a favorable safety profile.
BENZENESULFONAMIDE COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS
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Paragraph 0762-0763; 0813-0814, (2018/06/29)
This invention is directed to benzenesulfonamide compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment of diseases or conditions associated with voltage-gated sodium channels, such as epilepsy and/or epileptic seizure disorders.
Cycloalkane Derivatives
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Paragraph 0523; 0524, (2014/03/21)
Disclosed herein are therapeutic agents and/or preventive agents for pain or therapeutic agents and/or preventive agents for a sodium channel associated disease. The present invention provides compounds represented by the following formula (I) or pharmacologically acceptable salts thereof:
