2. Academic Validation
  3. Identification of pyrrolo[2,3-d]pyrimidines as potent HCK and FLT3-ITD dual inhibitors

Identification of pyrrolo[2,3-d]pyrimidines as potent HCK and FLT3-ITD dual inhibitors

  • Bioorg Med Chem Lett. 2017 Nov 15;27(22):4994-4998. doi: 10.1016/j.bmcl.2017.10.012.
Yasuko Koda 1,  Ko Kikuzato 1,  Junko Mikuni 2,  Akiko Tanaka 2,  Hitomi Yuki 3,  Teruki Honma 3,  Yuri Tomabechi 2,  Mutsuko Kukimoto-Niino 2,  Mikako Shirouzu 2,  Fumiyuki Shirai 1,  Hiroo Koyama 4
Affiliations

Affiliations

  • 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.
  • 4 Drug Discovery Chemistry Platform Unit, RIKEN Center for Life Science Technologies, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: hiroo.koyama@riken.jp.
PMID: 29037944 DOI: 10.1016/j.bmcl.2017.10.012
Abstract

A series of novel pyrrolo[2,3-d]pyrimidines were synthesized by introducing 15 different Amino acids to 7-cyclohexyl-5-(4-phenoxyphenyl)-7H-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 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); Pyrrolo[2,3-d]pyrimidine.

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