1446507-40-9Relevant articles and documents
Synthesis and Evaluation of a 18F-Labeled Triazinediamine Analogue for Imaging Mutant IDH1 Expression in Gliomas by PET
Chitneni, Satish K.,Yan, Hai,Zalutsky, Michael R.
, p. 606 - 611 (2018)
Mutations in the isocitrate dehydrogenase gene 1 (IDH1) are common in gliomas. Studies suggest that IDH1 mutations are early events in glioma formation and are important drivers of malignant progression. Herein, we report the synthesis and evaluation of a 18F-labeled triazinediamine analogue, [18F]1, as a candidate radiotracer for noninvasive imaging of IDH1 mutations in gliomas by positron emission tomography (PET). In vitro studies revealed good binding inhibition potency and binding affinity for [18F]1 in IDH1 mutant glioma cell lines, with a half-maximal inhibitory concentration value (IC50) of 54 nM and an equilibrium dissociation constant (Kd) of 40 nM. In vivo studies using mutant IDH1 glioma xenografts showed good tumor uptake of [18F]1 and specific inhibition by the unlabeled 1, but also elevated radioactivity uptake in the bone, suggesting significant defluorination. The results support further optimization of the triazinediamine scaffold to develop a more stable and potent 18F-labeled analogue for PET imaging of IDH1 mutations in gliomas.
IDH2 mutant inhibitor with macrocyclic structure, and medical applications thereof
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Paragraph 0047-0048; 0051-0052, (2020/05/29)
The present invention discloses a macrocyclic compound with a structure represented by a general formula (I), and a medical use thereof, or a pharmaceutically acceptable salt or solvate thereof, wherein L represents (CRaRb)n, 1-3 CRaRb groups can be replaced by O, NH, S or CH=CH, Z represents CRaRb, O, -NH-C(=O)-, -O-C(=O)- or -NH-, T is CH or N, X represents H, halogen, C3-C6 cycloalkyl, C1-C6 alkyl or C1-C6 haloalkyl, n is 4-10, and Ra and Rb are respectively and independently selected from H, halogen and C1-C6 alkyl. The inhibition effect of the macrocyclic compound provided by the invention on IDH2 is superior to the inhibition effect of the existing drug at a kinase level. According to the invention, the solubility of molecules and the overall fat solubility can be improved, so that the macrocyclic compound has the potential of penetrating through a blood-brain barrier, and is beneficial to solving the problem of brain tumors compared with the prior art.
Substituted triazine-based IDH inhibitor optical isomers and applications thereof
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, (2019/02/17)
The present invention belongs to the field of medical chemistry, and relates to a class of substituted triazine-based IDH inhibitor optical isomers and applications thereof, and specifically providesoptical isomers represented by a formula I or formula II or hydrates, solvates, crystals or pharmaceutically acceptable salts thereof, and a preparation method thereof, a pharmaceutical composition containing the optical isomers or hydrates, solvates, crystals or pharmaceutically acceptable salts thereof, and uses in treatment of cancer characterized by the presence of mutant isocitrate dehydrogenase 2. According to the present invention, the compounds have good inhibitory activity against IDH2, and can be used as the cancer treatment agents with advantages of high treatment effect and low side effect. The formulas I and II are defined in the specification.
