Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ
| Autor: | Michael J. Green, Roopa Rai, Kevin P. Quinn, Ashu Gupta, Jennifer Alfaro, Dhananjay I. Patel, David T. Hung, Stacy Kanno, Nitin Atmaram Randive, Emma McCullagh, Monali Banerjee, Anamika Thakur, Sarvajit Chakravarty, Anjan Kumar Nayak, Anil Agarwal, Ramona Almirez, Sweta Khare, Brahmam Pujala, Rambabu Guguloth, Sebastian Bernales, Sandip Middya, Mohd. Raja, Son Minh Pham, Bharat Uttam Shinde, Felipe Pérez de Arce, Arjun Surya, Patricio Avila |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification 010405 organic chemistry Kinase Organic Chemistry breakpoint cluster region Biology 01 natural sciences Biochemistry Pyrazolopyrimidine 0104 chemical sciences 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Enzyme chemistry P110δ hemic and lymphatic diseases Drug Discovery Cancer research biology.protein Bruton's tyrosine kinase Signal transduction PI3K/AKT/mTOR pathway |
| Zdroj: | ACS Medicinal Chemistry Letters. 7:1161-1166 |
| ISSN: | 1948-5875 |
| Popis: | The aberrant activation of B-cells has been implicated in several types of cancers and hematological disorders. BTK and PI3Kδ are kinases responsible for B-cell signal transduction, and inhibitors of these enzymes have demonstrated clinical benefit in certain types of lymphoma. Simultaneous inhibition of these pathways could result in more robust responses or overcome resistance as observed in single agent use. We report a series of novel compounds that have low nanomolar potency against both BTK and PI3Kδ as well as acceptable PK properties that could be useful in the development of treatments against B-cell related diseases. |
| Databáze: | OpenAIRE |
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