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 journalArticle

7 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 Jan 1

Fingerprint

Acute Myeloid Leukemia
Solubility
Derivatives
Thiazoles
Chemotherapy
Ports and harbors
Scaffolds
Hematopoietic Stem Cells
Drug Therapy
Mutation
thieno(2,3-d)pyrimidine

All Science Journal Classification (ASJC) codes

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

Cite this

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title = "Synthetic strategy for increasing solubility of potential FLT3 inhibitor thieno[2,3-d]pyrimidine derivatives through structural modifications at the C2and C6positions",
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.",
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Synthetic strategy for increasing solubility of potential FLT3 inhibitor thieno[2,3-d]pyrimidine derivatives through structural modifications at the C2and C6positions. / Oh, Changmok; Kim, Hyuntae; Kang, Jong Soon; Yun, Jieun; Sim, Jaejun; Kim, Hwan Mook; Han, Gyoonhee.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 3, 01.01.2017, p. 496-500.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthetic strategy for increasing solubility of potential FLT3 inhibitor thieno[2,3-d]pyrimidine derivatives through structural modifications at the C2and C6positions

AU - Oh, Changmok

AU - Kim, Hyuntae

AU - Kang, Jong Soon

AU - Yun, Jieun

AU - Sim, Jaejun

AU - Kim, Hwan Mook

AU - Han, Gyoonhee

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AB - 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.

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