Identification of pyrrolo[2, 3-d]pyrimidines as potent HCK and FLT3-ITD dual inhibitors. Issue 22 (15th November 2017)

• Record Type: Journal Article
• Authors: Koda, Yasuko; Kikuzato, Ko; Mikuni, Junko; Tanaka, Akiko; Yuki, Hitomi; Honma, Teruki; Tomabechi, Yuri; Kukimoto-Niino, Mutsuko; Shirouzu, Mikako; Shirai, Fumiyuki; Koyama, Hiroo
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 22(2017)
• Page Start: 4994
• Page End: 4998
• Publication Date: 2017-11-15
• Subjects: Acute myeloid leukemia (AML) -- FMS-like tyrosine kinase 3 with internal tandem duplication mutations (FLT3-ITD) -- Hematopoietic cell kinase (HCK) -- Pyrrolo[2, 3-d]pyrimidine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.10.012
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Identification of HCK and FLT3-ITD dual inhibitors. Abstract: A series of novel pyrrolo[2, 3- d ]pyrimidines were synthesized by introducing 15 different amino acids to 7-cyclohexyl-5-(4-phenoxyphenyl)-7 H -pyrrolo[2, 3- d ]pyrimidine-4-amine. Compounds with potent activities against HCK and FLT3-ITD were evaluated in viability studies with acute myeloid leukemia cell line MV4-11. Our structure activity relationship analyses lead to the identification of compound31, which exhibited potent HCK and FLT3-ITD inhibition and activity against the MV4-11 cell line.