HPLC of Formula: 930-36-9On September 24, 2020 ,《Discovery of DS-1971a, a Potent, Selective NaV1.7 Inhibitor》 was published in Journal of Medicinal Chemistry. The article was written by 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. The article contains the following contents:
A highly potent, selective NaV1.7 inhibitor, DS-1971a(I), has been discovered. Exploration of the left-hand Ph 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 Addnl., GSH adducts formation, which can cause idiosyncratic drug toxicity, was successfully avoided by this modification. An addnl. optimization led to the discovery of DS-1971a. In preclin. studies, DS-1971a demonstrated highly potent selective in vitro profile with robust efficacy in vivo. DS-1971a exhibited a favorable toxicol. 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. The experimental part of the paper was very detailed, including the reaction process of 1-Methylpyrazole(cas: 930-36-9HPLC of Formula: 930-36-9)
1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. HPLC of Formula: 930-36-9
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics