3-(2-Aminopyrimidin-4-yl)-[1,1′-biphenyl]-4-ols Derivatives: A Novel Class of Pim-1 Kinase Inhibitors
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Pim-1 kinase is emerging as an important new target for cancer therapy because it is associated with multiple cellular processes such as differentiation, proliferation, survival, apoptosis, and tumorigenesis. Inhibitors of Pim-1 kinase were designed and synthesized based on 2-(2-aminopyrimidin-4-yl)phenol (APP) scaffold. Introduction of 3-hydroxyaniline or 3-aminoaniline at 4-position of APP provided inhibitory activity against Pim-1 kinase. Additional substitutions at 5 position of 3-aminoaniline with amide were performed to study structure-activity relationship. Compound 7d and 7f showed submicromolar IC50 values against Pim-1 kinase.
Abstract
Pim-1 kinase is emerging as an important new target for cancer therapy because it is associated with multiple cellular processes such as differentiation, proliferation, survival, apoptosis, and tumorigenesis. Inhibitors of Pim-1 kinase were designed and synthesized based on 2-(2-aminopyrimidin-4-yl)phenol (APP) scaffold. Introduction of 3-hydroxyaniline or 3-aminoaniline at 4-position of APP provided inhibitory activity against Pim-1 kinase. Additional substitutions at 5 position of 3-aminoaniline with amide were performed to study structure-activity relationship. Compound 7d and 7f showed submicromolar IC50 values against Pim-1 kinase.
참고문헌 (17)
- Wang Z, "Pim-1: a serine", threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis, 2001, pp.2(3), 167~179
- Cibull TL, "Overexpression of Pim-1 during progression of prostatic adenocarcinoma", J Clin Pathol, 59(3), pp.285~288 (2006)
- Dhanasekaran SM, "Delineation of prognostic biomarkers in prostate cancer", Nature, 412(6849), pp.822~826 (2001)
- Amson R, "The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias", Proceedings of the National Academy of Sciences, 86(22), pp.8857~8861 (1989)
- Cohen AM, "Increased expression of the hPim-2 gene in human chronic lymphocytic leukemia and non-hodgkin lymphoma", Leuk Lymphoma, 45(5), pp.951~955 (2004)
- Huttmann A, "Gene expression signatures separate B-cell chronic lymphocytic leukaemia prognostic subgroups defined by ZAP-70 and CD38 expression status", Leukemia, 20(10), pp.1774~1782 (2006)
- van Lohuizen M, "Predisposition to lymphomagenesis in pim-1 transgenic mice : cooperation with c-myc and N-myc in murine leukemia virus-induced tumors", Cell, 56(4), pp.673~682 (1989)
- Larid PW, "In vivo analysis of Pim-1 deficiency", Nucleic Acids Res, 21(20), pp.4750~4755 (1993)
- Merkel AL, "PIM1 kinase as a target for cancer therapy", Expert Opinion on Investigational Drugs, 21(4), pp.425~436 (2012)
- Jacobs MD, "Pim-1 ligand-bound structures reveal the mechanism of serine", threonine kinase inhibition by LY294002, 2005, pp.280(14), 13728~13734
- Kumar A, "Crystal structures of proto-oncogene kinase Pim1 : a target of aberrant somatic hypermutations in diffuse large cell lymphoma", J Mol Biol, 348(1), pp.183~193 (2005)
- Qian KC, "Expression, purification, crystallization and preliminary crystallographic analysis of human Pim-1 kinase", Acta Crystallographica Section F Structural Biology and Crystallization Communications, 61(1), pp.96~99 (2005)
- Morwick T, "Pim kinase inhibitors: a survey of the patent literature", Expert Opinion on Therapeutic Patents, 20(2), pp.193~212 (2010)
- Blanco-Aparicio C, "Pim kinases in cancer: Diagnostic, prognostic and treatment opportunities", Biochem Pharmacol, 85(5), pp.629~643 (2013)
- Williams R, "Discontinued drugs in 2010: oncology drugs", Expert Opinion on Investigational Drugs, 20(11), pp.1479~1496 (2011)
- Suzuki A, "Cross-coupling reactions of organoboranes : an easy way to construct C-C bonds(nobel lecture)", Angew Chem Int Ed, 50(30), pp.6722~6737 (2011)
- Lee J, "Discovery of a novel class of 2-aminopyrimidines as CDK1 and CDK2 inhibitors", Bioorg Med Chem Lett, 21(14), pp.4203~4205 (2011)