A Competitive Edge: Competitor Inspired Scaffold Hopping in Herbicide Lead Optimization

Abstract

Over the years, scaffold hopping has proven to be a powerful tool in the agrochemical optimization process. It offers the opportunity to modify known molecular lead structures to improve a range of parameters, including biological efficacy and spectrum, physicochemical properties, toxicity, stability, and to secure new intellectual property. Very often the disclosure of a new chemical structure can spark a multitude of competitor activities, where scaffold hopping plays a crucial role in the optimization process as well as for the generation of new intellectual property. Herein, recent examples of scaffold hopping in early phase herbicide research based on competitor inspired activities will be discussed using examples of how these research campaigns can often result in the registration of new crop protection products.

Survey on the Recent Advances in 4-Hydroxyphenylpyruvate Dioxygenase (HPPD) Inhibition by Diketone and Triketone Derivatives and Congeneric Compounds: Structural Analysis of HPPD/Inhibitor Complexes and Structure–Activity Relationship Considerations

“…In this context, the search for new chemical entities that target HPPD is clearly needed. In recent years, many attempts were done to design new HPPD inhibitors with an improved herbicidal profile for weeds control, by application of the classical scaffold hopping approach 19 decorated by additional methods very useful in medicinal chemistry research, such as hybridization, molecular simplification, homologation, ring opening, etc.…”

In silico Evaluation of the Inhibitory Potential of Cymbopogonol from Cymbopogon citratus Towards Falcipain-2 (FP2) Cysteine Protease of Plasmodium falciparum

“…However, more studies on the aspect of lead optimization may be done for better in silico outcomes. 38 Prodrugs are inactive compounds that are created by chemically altering physiologically active molecules. 39 Therefore, inactive or less active derivatives of the potential inhibitor can be created towards increasing its lipophilicity and water solubility.…”

Inspired by Nature: Isostere Concepts in Plant Hormone Chemistry

“…Whether it be insufficient in vivo efficacy, a lack of selectivity, suboptimal physicochemical properties, adverse toxicological effects, metabolic stability issues, or narrow intellectual property (IP) space, researchers are always trying to find methods to improve the properties of their lead compounds . Of the synthetic methods available, isostere concepts or scaffold hopping offer attractive opportunities to solve these issues in agrochemical research via replacing a part of a molecule or altering the molecular architecture, resulting in an isofunctional molecule that exhibits similar or improved properties. , Herein, we outline recent advances in plant hormone chemistry exploiting isostere concepts to identify new lead structures for improved plant health, plant growth, or resilience against abiotic stress. It goes without saying that auxin is an essential plant hormone, but due to its well documented herbicidal effects, it will not be covered in this review.…”