Application of Molecular-Modeling, Scaffold-Hopping, and Bioisosteric Approaches to the Discovery of New Heterocyclic Picolinamides

Autor:	Victoria Jackson, Linda Jordan, Ryan N. Burgin, Oliver J. S. McGaw, Calum W. Muir, Victor Ceban
Rok vydání:	2022
Předmět:	Models Molecular Structure-Activity Relationship Antifungal Agents Molecular Structure Crop Protection General Chemistry Picolinic Acids General Agricultural and Biological Sciences
Zdroj:	Journal of Agricultural and Food Chemistry. 70:11031-11041
ISSN:	1520-5118 0021-8561
DOI:	10.1021/acs.jafc.2c03755
Popis:	Macrocyclic natural products and their derivatives are a valuable source for biologically active crop protection products and have had significant impact on the development of conventional agrochemicals. However, they can be challenging starting points for lead-generation efforts because of their size, structural complexity, and developability. Using molecular modeling and electrostatic analysis, alternative bicyclic isosteres were identified as replacements for the antifungal nine-membered macrocycle UK-2A. By application of a structure-based conformational approach, a series of heterocyclic replacements were derivatized to deliver promising fungicidal activity and scaffold bioisosteres were further diversified to investigate structure-activity relationships.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c96f33a0155184724408de59ab6a91d2 https://doi.org/10.1021/acs.jafc.2c03755 Zobrazit plný text záznamu