1360106-01-9Relevant academic research and scientific papers
Discovery of clinical candidate Sivopixant (S-600918): Lead optimization of dioxotriazine derivatives as selective P2X3 receptor antagonists
Fujii, Yasuhiko,Hirai, Keiichiro,Horiguchi, Tohru,Ichihashi, Yusuke,Itoh, Naohiro,Kai, Hiroyuki,Kameyma, Takayuki,Kasai, Erika,Kurose, Noriyuki,Minami, Kazuhisa,Murakami, Yuki,Nakamura, Kenichiroh,Ogawa, Hiroko,Onodera, Naohiro,Sekimoto, Ryouko,Shinohara, Shunji,Shintani, Takuya,Yoneda, Sosuke,Yoshida, Osamu
, (2021/10/04)
In previous work, we discovered a lead compound and conducted initial SAR studies on a novel series of dioxotriazines to identify the compound as one of the P2X3 receptor antagonists. This compound showed high P2X3 receptor selectivity and a strong analgesic effect. Although not selected for clinical development, the compound was evaluated from various aspects as a tool compound. In the course of the following study, the molecular structures of the dioxotriazines were modified based on pharmacokinetic/pharmacodynamic (PK/PD) analyses. As a result of these SAR studies, Sivopixant (S-600918) was identified as a clinical candidate with potent and selective antagonistic activity (P2X3 IC50, 4.2 nM; P2X2/3 IC50, 1100 nM) and a strong analgesic effect in the rat partial sciatic nerve ligation model (Seltzer model) of allodynia (ED50, 0.4 mg/kg).
AMINOTRIAZINE DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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, (2016/05/19)
The present invention provides novel compounds having a P2X3 and/or P2X2/3 receptor antagonistic activity. A compound of Formula (I): wherein Ra and Rb, and Rd and Re are taken together to
AMINO-TRIAZINE DERIVATIVES AND PHARMACEUTICAL COMPOSITION CONTAINING SAID DERIVATIVES
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, (2016/10/07)
The present invention provides novel compounds having a P2X 3 and/or P2X 2/3 receptor antagonistic activity. A compound of Formula (I): wherein R a and R b , and R d and R e are taken together to form oxo or the like; R 4a and R 4b are hydrogen or the lik
