Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 1: pyrido[2,3-b]pyrazines.
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.


CONCLUSIONS
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.
Crowley
Patrick J
PJ
Syngenta, Chemistry Department, Jealott Hill International Research Centre, Bracknell, Berkshire RG42 6EY, UK.
Lamberth
Clemens
C
Müller
Urs
U
Wendeborn
Sebastian
S
Nebel
Kurt
K
Williams
John
J
Sageot
Olivia-A
OA
Carter
Neil
N
Mathie
Tanya
T
Kempf
Hans-Joachim
HJ
Godwin
Jeremy
J
Schneiter
Peter
P
Dobler
Markus R
MR
D005658:Fungi / Q000187:drug effects; D005659:Fungicides, Industrial / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010935:Plant Diseases / Q000382:microbiology; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014908:Triticum / Q000382:microbiology; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D005659:Fungicides, Industrial; D011719:Pyrazines; D050257:Tubulin Modulators