Series of novel thiazolopyrimidineone compounds exhibiting herbicide activity targeting the KARI enzyme

Overview

This offering comprises a series of 19 novel thiazolopyrimidineone compounds developed in the laboratories of Professors Luke Guddat, Gary Schenk, and Ross McGeary at The University of Queensland. The compounds exhibit herbicide activity by targeting ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. While over 50 commercial herbicides target the first enzyme in this pathway (acetolactate synthase), KARI remains a comparatively underexplored target, presenting an opportunity for new modes of action in weed management. The series was developed through rational design guided by crystallographic data, including synchrotron-derived structural information on the target enzyme. Positive results have been obtained in enzyme inhibition screening assays and in tests against a panel of weed species.

Technical specifications

• Target: Ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway
• Compound series: 19 novel thiazolopyrimidineone analogues with systematic substituent variation
• Design approach: Structure-based rational design supported by crystallographic data, including synchrotron-derived target structures
• Validation status: Positive results in KARI enzyme inhibition screening assays
• Biological activity: Demonstrated activity against a panel of weed species
• Differentiation: Addresses an underexplored herbicide target site, with the potential for novel modes of action distinct from existing acetolactate synthase inhibitors

Technology readiness level

The compound series is at an early-to-mid stage of research and development. A screening hit against KARI has been confirmed, and a focused series of analogues with substituent variation has been synthesized and evaluated. Enzyme-level inhibition has been demonstrated, and preliminary testing against weed species has shown biological activity. Further validation work, including expanded weed-spectrum testing, selectivity assessment, and field-relevant formulation studies, would be required to advance the series toward commercial development.