Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic progenitor cells that cause bleeding, fatal infection, and organ infiltration with leukemic cells. Cytotoxic chemotherapy is often used for treat AML but limited by mutation of several genes. Especially, a mutation in FLT3 is commonly occurs and is associated with poor prognosis. Our previous research to identify FLT3 inhibitors showed that thieno[2,3- d]pyrimidine derivatives had an inhibitory activity against both wild type and mutant FLT3 and synthesized compound 1. Compound 1 exhibited stronger antiproliferative activity against MV4-11 cells than AC220, which is a well-known FLT3 inhibitor, and has good microsomal stability. However, compound 1 had poor solubility in PBS. We then carried out further structural modification at the C2 and the C6 positions of thieno[2,3-d]pyrimidine scaffold. Compound 13b, which has a thiazole moiety at the C2 position, exhibited better antiproliferative activity and better solubility than compound 1 and moderate microsomal stability. These results indicate that compound 13b could be a promising potential FLT inhibitor for AML chemotherapy.