78471-43-9Relevant articles and documents
Discovery and biological profile of isoindolinone derivatives as novel metabotropic glutamate receptor 1 antagonists: A potential treatment for psychotic disorders
Ito, Satoru,Hirata, Yukari,Nagatomi, Yasushi,Satoh, Atsushi,Suzuki, Gentaroh,Kimura, Toshifumi,Satow, Akio,Maehara, Shunsuke,Hikichi, Hirohiko,Hata, Mikiko,Ohta, Hisashi,Kawamoto, Hiroshi
, p. 5310 - 5313 (2009)
We describe here the discovery and biological profile of a series of isoindolinone derivatives as developed mGluR1 antagonists. Our combined strategy of rapid parallel synthesis and conventional medicinal optimization successfully led to N-cyclopropyl 22 and N-isopropyl isoindolinone analogs 21 and 23 with improved in vivo DMPK profiles. Moreover the most advanced analog 23 showed an oral antipsychotic-like effect at a dose of 1 mg/kg in an animal model.
CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia
Hansen, Joshua D.,Correa, Matthew,Alexander, Matt,Nagy, Mark,Huang, Dehua,Sapienza, John,Lu, Gang,Lebrun, Laurie A.,Cathers, Brian E.,Zhang, Weihong,Tang, Yang,Ammirante, Massimo,Narla, Rama K.,Piccotti, Joseph R.,Pourdehnad, Michael,Lopez-Girona, Antonia
, p. 1835 - 1843 (2021/03/09)
Acute myeloid leukemia (AML) is marked by significant unmet clinical need due to both poor survival and high relapse rates where long-term disease control for most patients with relapsed or refractory AML remain dismal. Inspired to bring novel therapeutic options to these patients, we envisioned protein degradation as a potential therapeutic approach for the treatment of AML. Following this course, we discovered and pioneered a novel mechanism of action which culminated in the discovery of CC-90009. CC-90009 represents a novel protein degrader and the first cereblon E3 ligase modulating drug to enter clinical development that specifically targets GSPT1 (G1 to S phase transition 1) for proteasomal degradation. This manuscript briefly summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and efficacy data for CC-90009, which is currently in phase 1 clinical development.
Aminopyrazine/pyridine compound and preparation method and application thereof
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Paragraph 0150-0152, (2020/05/05)
The invention discloses an aminopyrazine/pyridine compound and a preparation method and application thereof. Particularly, a pyrazine/pyridylamine compound shown as a general formula I, or pharmaceutically acceptable salt thereof, or enantiomer, diastereoisomer, tautomer, solvate, polymorphic substance or prodrug thereof, a preparation method thereof and application in pharmacy are disclosed, andthe definition of each group is shown in the specification.