121st General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Event Hall
Time 4월 19일 (목요일) 11:00~12:30
Code MEDI.P-641
Subject Discovery of novel N-cyclohexylpyrimidin-4-amine derivatives as Tyro3 kinase inhibitors
Authors DukWoon Kim, Hyeon Seok jung, YEONKYUNG LEE1, Jong Yeon Hwang2, Do Hyun Ryu, Sung Yun Cho3,*
Department of Chemistry, Sungkyunkwan University, Korea
1Chungnam National University, Korea
2Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Korea
3WCI, Korea Research Institute of Chemical Technology, Korea
Abstract The TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases (RTKs) are aberrantly expressed in multiple hematological and epithelial malignancies. TAM receptor and Gas 6 a ligand of TAM receptors, are overexpressed in a variety of solid tumors and hematological cancers. Of the TAM receptors, Axl receptor is overexpressed in tumor tissues, such as breast cancer, renal cell carcinoma, GBM, ovarian cancer, pancreatic cancer, and esophageal cancer. Mer receptor plays also major role in multiple myeloma and acute lymphoblastic leukemia, and has been elucidated as a novel therapeutic target in GBM. Tyro3 is less studied and recently identified as Tyro3 expression decreases survival of malignant melanoma cell. Recently, it has been reported that Tyro3 is being proposed as a drug target for breast cancer and colorectal cancer. Thus, regulating the function of Tyro3 could be an important therapeutics for the various cancer treatment. Moreover, it has been elucidated that Tyro3 plays a major roles in tumor micro-environment, deeply related with tumor associated macrophage (TAM). Thus, the development of selective inhibitors of TAM receptors, particularly Tyro3, has been considered as a possible methodology to overcome the side effects of TAM receptor inhibition and improve tumor micro-environment. In this report, we synthesized a series of novel N-cyclohexylpyrimidin-4-amine derivatives that were substituted with aniline moieties and evaluated for TAM kinase inhibitory activity and some of the compounds displayed excellent selectivity in vitro enzyme assay.
E-mail godejrwk@naver.com