Synthesis of Phthalimide Derivatives as Pim-1 Kinase Inhibitors
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Pim-1 kinase has emerged as an important target for cancer treatment due to its important roles in cell cycle progression and apoptosis inhibition, resulting in tumorigenesis. Inhibitors of Pim-1 kinase were designed and synthesized based on phthalimide scaffold. Attachment of the pyrazine, substituted with amino group at 6-position, to phthaimide provided the compounds showing inhibitory activity against Pim-1 kinase. Further exploration on the linker structure activity relationship (SAR) between amino group and pyrazine resulted in compounds with promising inhibitory activity. Compound 4d, 5-(6-(3-(diethylamino)propoxy)pyrazin-2-ylamino)isoindoline-1,3-dione, showed submicromolar IC50 value against Pim-1 kinase.
Abstract
Pim-1 kinase has emerged as an important target for cancer treatment due to its important roles in cell cycle progression and apoptosis inhibition, resulting in tumorigenesis. Inhibitors of Pim-1 kinase were designed and synthesized based on phthalimide scaffold. Attachment of the pyrazine, substituted with amino group at 6-position, to phthaimide provided the compounds showing inhibitory activity against Pim-1 kinase. Further exploration on the linker structure activity relationship (SAR) between amino group and pyrazine resulted in compounds with promising inhibitory activity. Compound 4d, 5-(6-(3-(diethylamino)propoxy)pyrazin-2-ylamino)isoindoline-1,3-dione, showed submicromolar IC50 value against Pim-1 kinase.
참고문헌 (15)
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