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Identification of pyrrolo[2,3-d]pyrimidines as potent HCK and FLT3-ITD dual inhibitors |
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| Authors: | Yasuko Koda Ko Kikuzato Junko Mikuni Akiko Tanaka Hitomi Yuki Teruki Honma Yuri Tomabechi Mutsuko Kukimoto-Niino Mikako Shirouzu Fumiyuki Shirai Hiroo Koyama |
| Institution: | 1. Drug Discovery Chemistry Platform Unit, RIKEN Center for Life Science Technologies, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan;2. Drug Discovery Structural Biology Platform Unit, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan;3. Drug Discovery Computational Chemistry Platform Unit, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan |
| Abstract: | A series of novel pyrrolo2,3-d]pyrimidines were synthesized by introducing 15 different amino acids to 7-cyclohexyl-5-(4-phenoxyphenyl)-7H-pyrrolo2,3-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 compound 31, which exhibited potent HCK and FLT3-ITD inhibition and activity against the MV4-11 cell line. |
| Keywords: | Acute myeloid leukemia (AML) FMS-like tyrosine kinase 3 with internal tandem duplication mutations (FLT3-ITD) Hematopoietic cell kinase (HCK) Corresponding author |
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