882678-96-8Relevant articles and documents
1,4,6-Trisubstituted imidazo[4,5-c]pyridines as inhibitors of Bruton's tyrosine kinase
Kraj?ovi?ová, Soňa,Jorda, Radek,Vanda, David,Soural, Miroslav,Kry?tof, Vladimír
, (2020/12/21)
Herein, we report an efficient synthetic approach towards trisubstituted imidazo [4,5-c]pyridines designed as inhibitors of Bruton's tyrosine kinase (BTK). Two alternative synthetic routes for the simple preparation of desired compounds with variable substitutions at the N1, C4, C6 positions were introduced with readily available building blocks. Further, the developed synthetic approach was feasible for isomeric compounds bearing imidazo [4,5-b]pyridine scaffolds. In contrast to expectations based on previous studies, the imidazo [4,5-c]pyridine inhibitor exhibited a significantly higher activity against BTK compared to its imidazo [4,5-b]pyridine isomer. An inherent SAR study in the series of imidazo [4,5-c]pyridine compounds revealed a remarkably high tolerance of C6 substitutions for both hydrophobic and hydrophilic substituents. Preliminary cellular experiments indicated selective BTK targeting in Burkitt lymphoma and mantle cell lymphoma cell lines. The inhibitors could thus serve as starting points for further development, eventually leading to BTK inhibitors that could be used after ibrutinib failure.
Compound capable of being used as immunomodulator, and preparation method and application thereof
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Paragraph 0094-0098, (2021/10/13)
The invention relates to a micromolecular immunomodulator and discloses a method for preparing the micromolecular immunomodulator at the same time, and the micromolecular immunomodulator can be used for treating cancers or tumors, infectious diseases, metabolic diseases and other diseases and has great clinical value.
Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton's Tyrosine Kinase (BTK)
Watterson, Scott H.,Liu, Qingjie,Beaudoin Bertrand, Myra,Batt, Douglas G.,Li, Ling,Pattoli, Mark A.,Skala, Stacey,Cheng, Lihong,Obermeier, Mary T.,Moore, Robin,Yang, Zheng,Vickery, Rodney,Elzinga, Paul A.,Discenza, Lorell,D'Arienzo, Celia,Gillooly, Kathleen M.,Taylor, Tracy L.,Pulicicchio, Claudine,Zhang, Yifan,Heimrich, Elizabeth,McIntyre, Kim W.,Ruan, Qian,Westhouse, Richard A.,Catlett, Ian M.,Zheng, Naiyu,Chaudhry, Charu,Dai, Jun,Galella, Michael A.,Tebben, Andrew J.,Pokross, Matt,Li, Jianqing,Zhao, Rulin,Smith, Daniel,Rampulla, Richard,Allentoff, Alban,Wallace, Michael A.,Mathur, Arvind,Salter-Cid, Luisa,Macor, John E.,Carter, Percy H.,Fura, Aberra,Burke, James R.,Tino, Joseph A.
, (2019/04/17)
Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fc receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacological inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clinical studies.