Innovation in insecticide discovery: Approaches to the discovery of new classes of insecticides.

The continuing demand for agrochemical insecticides that can meet increasing grower, environmental, consumer and regulatory requirements creates the need for the development of new solutions for managing crop pest insects. The development of resistance to the currently available insecticidal products adds another critical driver for new insecticidal active ingredients (AIs). One avenue to meeting these challenges is the creation of new classes of insecticidal molecules to act as starting points and prototypes stimulating further spectrum, efficacy and environmental impact refinements. A new class of insecticides is foreshadowed by the first molecule exemplifying that class (first-in-class, FIC) and offers one measure of innovation within the agrochemical industry. Most insecticides owe their discovery to competitor-inspired (i.e. competitor patents/products) or next-generation (follow-on to a company's pre-existing product) strategies. In contrast, FIC insecticides primarily emerge from a bioactive hypothesis approach, with the largest segment resulting from the exploration of new areas of chemistry/heterocycles and underexploited motifs. Natural products also play an important role in the discovery of FIC insecticides. Understanding the origins of these FIC compounds and the approaches used in their discovery can provide insights into successful strategies for future FIC insecticides. This review analyses information on historic and recently introduced FIC insecticides. Its main objective has been to identify the most successful discovery strategies for identifying new agrochemical solutions to meet the challenge of minimizing crop losses resulting from insects. © 2022 Society of Chemical Industry.

Impact of natural products on discovery of, and innovation in, crop protection compounds.

Natural products (NPs) have long been an important source of, and inspiration for, developing novel compounds to control weeds, pathogens and insect pests. In this review, we use a dataset of 800 historic, current and emerging crop protection compounds to explore the influence of NPs on the introduction of new crop protection compounds (fungicides, herbicides, insecticides) as a function of time. NPs, their semisynthetic derivatives (NPDs) and compounds inspired by NPs (NP mimics, NPMs) account for 17% of all crop protection compounds. NPs, NPDs, and NPMs have been a fairly constant source of new agrochemicals over the past 70 years. NP synthetic equivalents (NPSEs) is a fourth group of NP-related crop protection compounds composed of synthetic compounds which by chance also happen to have an NP model (but are not involved in the discovery). If NPSE compounds are also included, then 50% of all crop protection compounds hypothetically could have had a NP origin. Similar trends also hold true for the impact of NPs on the discovery of new modes of action (MoA) or innovation in crop protection compounds as measured by the number of first-in-class compounds. NPs have had the largest impact on the numbers and global sales (2018 USD) of insecticides compared to fungicides and herbicides. The present analysis highlights NPs as a long-standing and continuing source of new chemistry, new MoAs and innovation in crop protection compound discovery. © 2021 Society of Chemical Industry.

East meets west: regional impact on agrochemical discovery and innovation.

The efficient production of the food needed to nourish an expanding global population continues to fuel the demand for new crop protection compounds. This task is made all the more difficult by the need to meet increasingly demanding grower, consumer and regulatory constraints. The discovery and development of new synthetic organic crop protection compounds has been largely the responsibility of the agrochemical industry in Europe, Japan and the USA, with government-funded academic research often playing a crucial role in the early stages of the invention and testing of novel activity. The way in which this process takes place has undergone a dramatic evolution over the past 75 years. Drastic consolidation and globalization among the research and development (R&D)-based companies in these regions have characterized these changes. This evolution in the agrochemical industry has, in turn, shaped the rate of introduction and geographic origin of new crop protection compounds. In spite of these changes, the rate of invention of new classes of crop protection compounds has remained relatively constant. During the past 30 years, the forefront of new compound introductions has moved towards Asia, and Japan in particular. Although there are now more agrochemical companies in Japan involved in the discovery and development of new crop protection compounds than in Europe and the USA combined, on a compound-per-company basis, US companies currently generate the highest output. However, it is expected that there will continue to be changes in the numbers and origins of new crop protection compounds, with contributions continuing from Europe, Japan and the USA, and increasingly from China. © 2021 Society of Chemical Industry.

Crop protection compounds - trends and perspective.

The Industry responsible for the discovery and development of crop protection compounds has undergone dramatic changes and increasing consolidation since the initial innovations in synthetic organic fungicides, herbicides and insecticides in the late 1940s and early 1950s. Likewise, there have been striking changes in the rate of introduction of new crop protection compounds over the past 70 years. While numerous studies over the past five decades have signaled the ongoing decline in the numbers of new active ingredients (AIs), a detailed analysis of the trends in the rate of introduction of crop protection compounds shows a more complex pattern in the overall output of new AIs. The recent (post-2000) decline in the numbers of new herbicides is the primary source of the perceived decline in overall numbers. When herbicides are excluded, the output of new fungicides and insecticides has been relatively constant, especially for the past 20 years. A notable observation is that innovation, as measured by the number of compounds representing a new chemical class (First-in-Class) has been relatively constant for the past 70 years, and most recently has been driven by the appearance of new fungicides and insecticides. Thus, the discovery and development of new AIs for crop protection and public health continues, in spite of the many challenges and changes to the Industry. © 2021 Society of Chemical Industry.

Crop Protection Discovery: Is Being the First Best?

Current crop protection chemicals span an array of chemistry classes and modes of action. Typically, within each chemistry class, there are multiple chemically distinct active ingredients competing with each other for market position. In this competition, the first product to market in a new class or mode of action may or may not have an advantage depending upon a number of parameters, including relative efficacy against the target pests, pest resistance, regulatory pressures, synthetic complexity, and marketing effectiveness. The number of companies involved in the discovery of new crop protection compounds has been declining, and patenting strategies have become more sophisticated, making it more challenging to break into an existing area of chemistry. One result is new classes of chemistry tend to be smaller, making first to market more beneficial than in the past. Additionally, the first into a market with a new class of chemistry has the opportunity to set positioning and expectations.

The ABCs of pesticide toxicology: amounts, biology, and chemistry.

Everyone is affected directly or indirectly by pesticide use and safety. The magnitude and perception of this effect depend on one's individual involvement or vantage point. The researcher seeks discovery and the entrepreneur goes after financial rewards. The general public wants food, health and safety. Pesticide toxicology is a core issue in these relationships. The three goals of toxicology research on pesticides are first to create new knowledge and chemicals, second to evaluate their effectiveness and safety and third to regulate their use. What amounts of pesticides are applied and do we really understand their biology and chemistry? This review addresses the ABCs of pesticide toxicology, i.e. their amounts, biology and chemistry.