120th General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Exhibition Hall 2+3
Time 10월 19일 (목요일) 11:00~12:30
Code MEDI.P-333
Subject 4-Phenylamino-1H-pyrazolo[3,4-d]pyrimidin-4-yl-acrylamide derivatives as novel irreversible Bruton’s tyrosine kinase inhibitors and their biological activities
Authors DukWoon Kim, Hyeon Seok jung, Jong Yeon Hwang1, PILHO KIM1, jae du ha2, do hyun ryu, Sung Yun Cho2,*
Department of Chemistry, Sungkyunkwan University, Korea
1Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Korea
2WCI, Korea Research Institute of Chemical Technology, Korea
Abstract Bruton’s tyrosine kinase (BTK), a non-receptor tyrosine kinase, plays major roles in the B cell receptor signal transduction pathways regulating activation, survival, proliferation, and differentiation of B-lineage lymphoid cells. Mutations in gene encoding human BTK lead to X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Dysregulation of BTK signaling pathway is implicated with the pathogenesis of B cell lymphoma because B cells play a central role in the pathogenesis of several autoimmune diseases and B cell malignancies. Indeed, there have been tremendous number of clinical trials for either monotherapy or combined with other possible treatment, and inhibition of BTK has been considered as an effective and attractive therapeutic target for B cell related malignancies. In this report, we synthesized a series of novel 4-phenylamino-1H-pyrazolo[3,4-d]pyrimidin-4-yl-acrylamide derivatives that were substituted with phenyl moieties and evaluated BTK kinase inhibitory activity and cell based proliferation assay. Some of the compounds displayed excellent activity in vitro enzyme and cell-based assay.
E-mail godejrwk@naver.com