Synthesis and anthelmintic activity of thioamide analogues of cyclic octadepsipeptides such as PF1022A.
The tetra- and mono-thionated cyclic octadepsipeptides represent novel cyclic octadepsipeptide derivatives with broad-spectrum activity against parasitic nematodes in mice and sheep. Some of these show better activity than the potent natural anthelmintic cyclic octadepsipeptide PF1022A against Hymenolepis nana, Heterakis spumosa and Trichinella spiralis larvae in mice. In particular, they show improved efficacy against Haemonchus contortus and Trichostrongylus colubriformis in sheep compared with PF1022A. Here we report on two different and simple synthetic pathways for this new class of thionated cyclic octadepsipeptides.
Jeschke
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P
Bayer AG, Crop Protection Business Group, Agricultural Centre Monheim, D-51368 Leverkusen, Germany. peter.jeschke.pj@bayer-ag.de
Harder
A
A
Etzel
W
W
Gau
W
W
Thielking
G
G
Bonse
G
G
Iinuma
K
K
D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D047630:Depsipeptides; D006374:Helminthiasis, Animal / Q000188:drug therapy; D006376:Helminths / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D012756:Sheep; D013329:Structure-Activity Relationship; D013854:Thioamides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D000871:Anthelmintics; D047630:Depsipeptides; D010456:Peptides, Cyclic; D013854:Thioamides; C075544:PF 1022A