Synthetic strategy for increasing solubility of potential FLT3 inhibitor thieno[2,3-d]pyrimidine derivatives through structural modifications at the C2and C6positions

Changmok Oh, Hyuntae Kim, Jong Soon Kang, Jieun Yun, Jaejun Sim, Hwan Mook Kim, Gyoonhee Han

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic progenitor cell. In AML, a mutation in FLT3 is commonly occurs and is associated with poor prognosis. We have previously reported that thieno[2,3-d]pyrimidine derivative compound 1 exhibited better antiproliferative activity against MV4-11 cells which harbor mutant FLT3 than AC220, which is a well-known FLT3 inhibitor, and has good microsomal stability. However, compound 1 had poor solubility. We then carried out further structural modification at the C2and the C6positions of thieno[2,3-d]pyrimidine scaffold. Compound 13b, which possesses a thiazole moiety at the C2position, exhibited better antiproliferative activity than compound 1 and showed increased solubility and moderate microsomal stability. These results indicate that compound 13b could be a promising potential FLT inhibitor for AML chemotherapy.

Original languageEnglish
Pages (from-to)496-500
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number3
DOIs
Publication statusPublished - 2017

Bibliographical note

Funding Information:
This research was supported by a grant from the Translational Research Center for Protein Function Control (Grant NRF-2009-0083522), the Ministry of Science, ICT and Future Planning (Grant NRF-2013M3A6A4072536), the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1324), and the KRIBB Research Initiative Program.

Publisher Copyright:
© 2016 Elsevier Ltd

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Synthetic strategy for increasing solubility of potential FLT3 inhibitor thieno[2,3-d]pyrimidine derivatives through structural modifications at the C<sub>2</sub>and C<sub>6</sub>positions'. Together they form a unique fingerprint.

Cite this