Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 1: pyrido[2,3‐b]pyrazines |
| |
Authors: | Patrick J Crowley Dr Clemens Lamberth Urs Müller Sebastian Wendeborn Kurt Nebel John Williams Olivia‐A Sageot Neil Carter Tanya Mathie Hans‐Joachim Kempf Jeremy Godwin Peter Schneiter Markus R Dobler |
| |
Affiliation: | 1. Syngenta, Chemistry Department, Jealott Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK;2. Syngenta Crop Protection AG, Research Chemistry, Schaffhauserstr. 101, CH‐4332 Stein, Switzerland;3. Syngenta Crop Protection AG, Research Biology, Schaffhauserstr. 101, CH‐4332 Stein, Switzerland;4. Novartis Institute for BioMedical Research Inc., 250 Massachusetts Avenue, Cambridge, MA 02139, USA |
| |
Abstract: | BACKGROUND: The excellent fungicidal activity of [1,2,4]triazolo[1,5‐a]pyrimidines suggested the search for further analogues with improved properties. RESULTS: A series of novel trisubstituted pyrido[2,3‐b]pyrazines has been designed and prepared as 6,6‐biheterocyclic analogues of related 5,6‐bicyclic [1,2,4]triazolo[1,5‐a]pyrimidines. Their fungicidal activity was evaluated against the plant pathogens Puccinia recondita Rob. ex Desm. f. sp. tritici (Eriks.) CO Johnston (wheat brown rust), Mycosphaerella graminicola (Fuckel) Schroter (Septoria tritici Rob., leaf spot of wheat) and Magnaporthe grisea (Hebert) Barr (Pyricularia oryzae Cav., rice blast). Structure–activity relationship studies revealed the advantage of a fluoro substituent in position 6 and of a secondary amine in position 8. CONCLUSION: 8‐Amino‐7‐aryl‐6‐halogen‐substituted pyrido[2,3‐b]pyrazines have been prepared as 6,6‐biheterocyclic analogues of similarly substituted triazolopyrimidine fungicides. A concise four‐step synthesis route has been worked out to prepare these novel compounds from commercially available starting materials. [(R)‐(1,2‐Dimethylpropyl)]‐[6‐fluoro‐7‐(2,4,6‐trifluorophenyl)pyrido[2,3‐b]pyrazin‐8‐yl]amine showed excellent activity against three economically important phytopathogens. Copyright © 2009 Society of Chemical Industry |
| |
Keywords: | fungicides pyridopyrazine heterocycle Niementowski reaction tubulin polymerisation Septoria tritici |
|
|