S-benzylisothiourea derivatives as small-molecule inhibitors of indoleamine-2,3-dioxygenase.
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.
Matsuno
Kenji
K
Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
Takai
Kazushige
K
Isaka
Yoshinobu
Y
Unno
Yuka
Y
Sato
Masayuki
M
Takikawa
Osamu
O
Asai
Akira
A
D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D013890:Thiourea