Synthesis and biological evaluation of xanthine derivatives with phenacyl group as tryptophan hydroxylase 1 (TPH1) inhibitors for obesity and fatty liver disease

Jihyeon Yoon, Won Il Choi, Saravanan Parameswaran, Gwi Bin Lee, Byeong Wook Choi, Pyeongkeun Kim, Dae Seop Shin, Ha Neul Jeong, Seung Mi Lee, Chang Ju Oh, Jae Han Jeon, In Kyu Lee, Myung Ae Bae, Hail Kim, Jin Hee Ahn

Research output: Contribution to journalArticlepeer-review

Abstract

Tryptophan hydroxylase 1 (TPH1) has emerged as a target for the treatment of metabolic diseases including obesity and fatty liver disease. A series of xanthine derivatives were synthesized and evaluated for their TPH1 inhibition. Among the synthesized compounds, compound 40 showed good in vitro activity and liver microsomal stability. Docking studies revealed that compound 40 showed better binding to TPH1 via key intermolecular interactions involving the xanthine scaffold, imidazo-thiazolyl ring, and hydroxyl-containing phenacyl moiety. In addition, compound 40 effectively suppressed the adipocyte differentiation of 3 T3-L1 cells.

Original languageEnglish
Article number129461
JournalBioorganic and Medicinal Chemistry Letters
Volume94
DOIs
StatePublished - 1 Oct 2023

Keywords

  • Fatty liver
  • Obesity
  • TPH inhibitor
  • Xanthine

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