2. Academic Validation
  3. Design and synthesis of imidazo[2,1-b]thiazole derivatives as potent and selective phosphatidylinositol 4-kinase IIIβ inhibitors for antiviral activity

Design and synthesis of imidazo[2,1-b]thiazole derivatives as potent and selective phosphatidylinositol 4-kinase IIIβ inhibitors for antiviral activity

  • Bioorg Med Chem Lett. 2025 Dec 1:128:130346. doi: 10.1016/j.bmcl.2025.130346.
Koji Ochiai 1,  Masahiko Kinebuchi 2,  Takekazu Kondo 2,  Takahiro Suezawa 2,  Morio Higuchi 2,  Motomichi Fujita 2,  Akinobu Yokoyama 2,  Hitomi Matsui 2,  Makoto Rembutsu 2,  Yuji Ishibashi 2,  Yuta Tanaka 2,  Aki Yonezawa 2,  Hirotaka Ando 2,  Yoshiaki Kitamura 2,  Michiaki Nagasawa 2,  Masahiro Ueno 2
Affiliations

Affiliations

  • 1 Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan. Electronic address: kouji.ochiai@mb.kyorin-pharm.co.jp.
  • 2 Watarase Research Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan.
PMID: 40701196 DOI: 10.1016/j.bmcl.2025.130346
Abstract

The type III phosphatidylinositol 4-kinase beta (PI4KB, PI4KIIIβ) is a lipid kinase that catalyzes the phosphorylation of phosphatidylinositol at the 4-position. PI4KB is widely understood to play a critical role in supporting viral replication, and PI4KB inhibitors are under investigation as potential host-targeting antivirals. In this study, we report potent and selective imidazo[2,1-b]thiazole inhibitors of PI4KB with Antiviral activity. Guided by ligand efficiency, optimization efforts yielded potent PI4KB inhibitors, and reducing proton donor count enhanced cellular potency (anti HRV: EC50 0.027 μM for compound 29, 0.007 μM for compound 30). Furthermore, compound 30 selectively inhibited PI4KB, with minimal off-target kinase activity, as confirmed by profiling.

Keywords

HRV; Host-targeting antiviral; Imidazo[2,1-b]thiazole; Lipid kinase; PI4KB.

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