Synthetic strategy for increasing solubility of potential FLT3 inhibitor thieno[2,3-d]pyrimidine derivatives through structural modifications at the C2 and C6 positions

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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 C2 and C6 positions
Author(s)
C Oh; H Kim; Jong Soon Kang; Ji Eun Yun; J Sim; H M Kim; G Han
Bibliographic Citation
Bioorganic & Medicinal Chemistry Letters, vol. 27, no. 3, pp. 496-500
Publication Year
2017
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
Keyword
Acute myeloid leukemia (AML)FLT3SolubilityThieno[2,3-d]pyrimidine
ISSN
0960-894X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bmcl.2016.12.034
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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