S-benzylisothiourea derivatives as small-molecule inhibitors of indoleamine-2,3-dioxygenase

Kenji Matsuno; Kazushige Takai; Yoshinobu Isaka; Yuka Unno; Masayuki Sato; Osamu Takikawa; Akira Asai

doi:10.1016/j.bmcl.2010.07.025

S-benzylisothiourea derivatives as small-molecule inhibitors of indoleamine-2,3-dioxygenase

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5126-9. doi: 10.1016/j.bmcl.2010.07.025. Epub 2010 Jul 11.

Authors

Kenji Matsuno¹, Kazushige Takai, Yoshinobu Isaka, Yuka Unno, Masayuki Sato, Osamu Takikawa, Akira Asai

Affiliation

¹ Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.

PMID: 20688518
DOI: 10.1016/j.bmcl.2010.07.025

Abstract

S-benzylisothiourea 3a was discovered by its ability to inhibit indoleamine-2,3-dioxygenase (IDO) in our screening program. Subsequent optimization of the initial hit 3a lead to the identification of sub-muM inhibitors 3r and 10h, both of which suppressed kynurenine production in A431 cells. Synthesis and structure-activity relationship of S-benzylisothiourea analogues as small-molecule inhibitors of IDO are described.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
Structure-Activity Relationship
Thiourea / chemistry
Thiourea / pharmacology*

Substances

Enzyme Inhibitors
Indoleamine-Pyrrole 2,3,-Dioxygenase
Thiourea