- Development of a Scalable Method for Manufacturing the Central Core of CD73 Inhibitor AB680
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AB680 is a highly potent CD73 small molecule inhibitor discovered and developed by Arcus Biosciences, currently in clinical trials for the treatment of pancreatic cancer. Here, we report the development of a scalable and practical method for the manufacturing of the azaindazole central core. This synthesis features an N-oxide formation followed by an α-chlorination with POCl3 leading to the formation of 4,6-dichloro-1H-pyrazolo[3,4-b]pyridine 1 in high yield and 99.5% UV purity. This method was successfully performed on multikilogram scale to support the synthesis of AB680.
- Fournier, Jeremy,Yan, Xuelei,Tran, Anh T.,Grange, Rebecca L.,Jacob, Steven D.,Kalisiak, Jaroslaw,Lawson, Kenneth V.,Connor, Eric F.,Leleti, Manmohan R.,Powers, Jay P.
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p. 157 - 162
(2021/01/09)
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- Synthetic method for 6-chloro-1H-pyrazolo[3,4-B]pyridine
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The invention discloses a synthetic method for 6-chloro-1H-pyrazolo [3,4-B]pyridine. The synthetic method has the advantages that 2,6-dichloro-3-pyridinecarboxaldehyde and hydrazine hydrate which arecheap and easily obtained are taken as raw materials so as to prepare the 6-chloro-1H-pyrazolo[3,4-B]pyridine, the yield is not lower than 70%, the synthetic reaction conditions are mild, the purification is simple, a product is prepared with relatively high yield and high purity, the synthetic method is suitable for process scale-up, and therefore the problems that in the prior art, the raw materials are expensive, and the yield is low can be solved.
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Paragraph 0022; 0023; 0025-0036
(2018/10/19)
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- Heterocyclic compound used as MNK inhibitor
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The invention relates to a heterocyclic compound, a pharmaceutical composition containing the heterocyclic compound, a preparation method thereof, and application thereof used as a mitogen activated protein kinase interacting kinase 1 and 2-MNK1/MNK2 inhibitor. The inhibitor is the heterocyclic compound as shown in the formula (I), or its pharmaceutically acceptable salt, prodrug, solvent compound, polycrystal, isomer, stable isotope derivative or a pharmaceutical composition containing the heterocyclic compound. The compound of the invention can be used for treating or preventing MNK-mediatedrelated diseases, such as cancers.
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Paragraph 0214
(2019/01/08)
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- INDAZOLE AND AZAINDAZOLE COMPOUNDS AS IRAK-4 INHIBITORS
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The present invention provides indazole and aza indazole compounds of formula (I) or (II) and pharmaceutically acceptable salts thereof, and their use to inhibit IRAK-4 and/or for the treatment of diseases or disorders induced by IRAK-4.
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Page/Page column 66
(2017/02/09)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE
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Disclosed herein are compounds that inhibit Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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Paragraph 00851
(2016/01/25)
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- HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF
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Provided herein are heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and neurological disorders, including, but not limited to, e.g., psychosis, schizophrenia, depression, movement disorders, and Parkinson's disease.
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Paragraph 00254; 00257
(2013/12/03)
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- Compounds as syk kinase inhibitors
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The present invention relates to a compound of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by inhibition of Syk kinase.
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Paragraph 0770; 0771
(2013/03/26)
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