185041-05-8Relevant articles and documents
Synthesis of 4,5-disubstituted benzo[c][2,7]naphthyridines by combined metalation-palladium-catalysed cross-coupling strategies. Preparation of 8H-pyrido[4,3,2-mn]acridone as a model of cystodytin alkaloids
Guillier,Nivoliers,Cochennec,Godard,Marsais,Queguiner
, p. 4421 - 4436 (1996)
A short and efficient synthesis of 8H-pyrido[4,3,2-mn]acridone is described. The strategy involves the preparation of 4-chloro-5-methylbenzo[c][2,7]naphthyridine, as key intermediate, by metalation and Palladium catalyzed cross-coupling reaction. A second cross-coupling reaction and subsequent oxidation by SeO2 led to the title compound.
Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK)
Lam, Betty,Arikawa, Yasuyoshi,Cramlett, Joshua,Dong, Qing,de Jong, Ron,Feher, Victoria,Grimshaw, Charles E.,Farrell, Pamela J.,Hoffman, Isaac D.,Jennings, Andy,Jones, Benjamin,Matuszkiewicz, Jennifer,Miura, Joanne,Miyake, Hiroshi,Natala, Srinivasa Reddy,Shi, Lihong,Takahashi, Masashi,Taylor, Ewan,Wyrick, Corey,Yano, Jason,Zalevsky, Jonathan,Nie, Zhe
supporting information, p. 5947 - 5950 (2016/12/06)
Spleen Tyrosine Kinase (SYK) is a non-receptor cytoplasmic tyrosine kinase that is primarily expressed in hematopoietic cells. SYK is a key mediator for a variety of inflammatory cells, including B cells, mast cells, macrophages and neutrophils and therefore, an attractive approach for treatment of both inflammatory diseases and oncology indications. Using in house co-crystal structure information, and structure-based drug design, we designed and optimized a novel series of heteroaromatic pyrrolidinone SYK inhibitors resulting in the selection of the development candidate TAK-659. TAK-659 is currently undergoing Phase I clinical trials for advanced solid tumor and lymphoma malignancies, a Phase Ib study in advanced solid tumors in combination with nivolumab, and PhIb/II trials for relapsed/refractory AML.
FUSED HETEROAROMATIC PYRROLIDINONES
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, (2011/07/06)
Disclosed are compounds of Formula 1, and pharmaceutically acceptable salts thereof, wherein G, L1, L2, R1, R2, R3, and R4 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, pharmaceutical compositions containing them, and their use for treating disorders, diseases, and conditions involving the immune system and inflammation, including rheumatoid arthritis, hematological malignancies, epithelial cancers (i.e., carcinomas), and other disorders, diseases, and conditions for which inhibition of SYK is indicated.
