| Autor: |
Joel C. Barrish, John Hynes, Ajay Saxena, Natesan Murugesan, Dianlin Xie, Anjaneya Chimalakonda, Stefan Ruepp, Mitalee Das, Richard Rampulla, Durgarao Kantheti, Chunhong Yan, Julie Carman, Jignesh Nagar, Siva Subramani, Qian Ruan, William J. Pitts, Rajeev S. Bhide, Paul A. Elzinga, Venkatram Reddy Paidi, John S. Sack, Mark Fereshteh, Thangavel Soodamani, Amrita Jha Mukherjee, T. Thanga Mariappan, Ramesh Kumar Sistla, Kaushik Ghosh, Debarati Mazumder, Kamalavenkatesh Palanisamy, Deborah A. Holloway, Susan E. Kiefer, John A. Newitt, Satheesh Kesavan Nair, Polimera Subba Rao, Shailesh Dudhgoankar, Percy H. Carter, Xin Li, Srinivas Maddi, S. Pon Saravanakumar, Sreekantha Ratna Kumar, Sucharita Bose |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
ACS Med Chem Lett |
| ISSN: |
1948-5875 |
| Popis: |
[Image: see text] IRAK4 is an attractive therapeutic target for the treatment of inflammatory conditions. Structure guided optimization of a nicotinamide series of inhibitors has been expanded to explore the IRAK4 front pocket. This has resulted in the identification of compounds such as 12 with improved potency and selectivity. Additionally 12 demonstrated activity in a pharmacokinetics/pharmacodynamics (PK/PD) model. Further optimization efforts led to the identification of the highly kinome selective 21, which demonstrated a robust PD effect and efficacy in a TLR7 driven model of murine psoriasis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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