Indazole derivatives as partial agonists of PPAR(GAMMA) for the treatment of diabetes
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- TECH UNIV EINDHOVEN
- Filing Date
- 2026-01-07
- Publication Date
- 2026-07-16
AI Technical Summary
Current PPARγ full agonists used for treating type 2 diabetes cause undesired side effects such as weight gain, osteoporosis, and heart failure, while partial activation is known to induce insulin-sensitizing effects without these issues, but there is a need for compounds that bind strongly to PPARγ with controlled activation.
Development of a library of ligands that bind potently to PPARγ but do not fully activate the receptor, utilizing a unique binding mode that extends into all three arms of the ligand binding pocket, leveraging the MRL871 structure for rational design and synthesis, including a new synthetic route using N-tosylhydrazones and nitroarenes to form IH-indazoles.
The new ligands demonstrate improved potency, partial agonism, and receptor selectivity, reducing side effects and enhancing therapeutic efficacy for conditions like type 2 diabetes, obesity, and lipid disorders, with compounds like 13 showing low nanomolar affinity and partial coactivator recruitment comparable to benchmark partial agonist MRL24.
Smart Images
Figure IB2026050111_16072026_PF_FP_ABST