Investigating the C2 Modulation of the Imidazo[1,2-a]pyrazine-Based Hit Compound CTN1122: Synthesis, in vitro Antileishmanial Activity, Cytotoxicity and Casein Kinase 1 Inhibition.

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Tác giả: Stéphane Bach, Blandine Baratte, Marc-Antoine Bazin, Guillaume Bernadat, Christian Cavé, Sandrine Cojean, Khadidiatou Gassama, Patrice Le Pape, Olivier Leclercq, Cédric Logé, Philippe M Loiseau, Pascal Marchand, Fabrice Pagniez, Carine Picot, Najma Rachidi, Thomas Robert, Jérôme Thiéfaine, Lhana Tisseur, Christophe Tomasoni

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Germany : ChemMedChem , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 715957

Our research group previously discovered CTN1122, an imidazo[1,2-a]pyrazine compound with promising antileishmanial activity against intramacrophage amastigotes of Leishmania major and L. donovani strains. CTN1122 effectively targets Leishmania casein kinase 1 (L-CK1.2) and exhibits a favorable safety profile. To further explore its chemical space, we developed a convergent strategy to modify the C2 position of the imidazo[1,2-a]pyrazine core using Suzuki-Miyaura coupling of the corresponding triflate intermediate. Among 15 newly synthesized analogs, seven derivatives featuring variously substituted phenyl rings at C2 demonstrated L-CK1.2 inhibition within micromolar to submicromolar ranges and antileishmanial activity in vitro with low cytotoxicity in macrophages. Compounds 7 d and 7 l were particularly potent, with IC
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