Novel candesartan derivatives as indoleamine 2,3-dioxygenase inhibitors

Kenji Matsuno; Hiroshi Yamazaki; Yoshinobu Isaka; Kazushige Takai; Yuka Unno; Naohisa Ogo; Yoshinobu Ishikawa; Satoshi Fujii; Osamu Takikawa; Akira Asai

doi:10.1039/C2MD00278G

Novel candesartan derivatives as indoleamine 2,3-dioxygenase inhibitors†

Kenji Matsuno,^a Hiroshi Yamazaki,^a Yoshinobu Isaka,^a Kazushige Takai,^a Yuka Unno,^a Naohisa Ogo,^a Yoshinobu Ishikawa,^a Satoshi Fujii,^a Osamu Takikawa^b and Akira Asai*^a

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^a Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Japan
E-mail: aasai@u-shizuoka-ken.ac.jp
Fax: +81-54-264-5231
Tel: +81-54-264-5231

^b National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Obu, Aichi, Japan

Abstract

IDO is considered a promising therapeutic target for immunological cancer treatment. We found that the antihypertensive agent candesartan cilexetil inhibits IDO. The structural modifications provided a >10-fold more potent inhibitor. Structure–activity relationship and docking studies suggested that candesartan analogues uniquely bind to the entrance of the active site in IDO, and not to the haem region. Analogue synthesis, kinetic analysis and cellular activity are also described herein.

MedChemComm

Novel candesartan derivatives as indoleamine 2,3-dioxygenase inhibitors†

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Novel candesartan derivatives as indoleamine 2,3-dioxygenase inhibitors

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