title: Synthesis of anthelmintically active N-methylated amidoxime analogues of the cyclic octadepsipeptide PF1022A.
abstract: The N-methylated amidoxime analogues of the cyclic octadepsipeptide PF1022A represent novel derivatives with activity against Trichinella spiralis Owen and Nippostrongylus brasiliensis Lane in vitro and against parasitic nematodes in mice and sheep. Some of them show better activity against Hymenolepis nana Siebold, Heterakis spumosa Schneider and Heligmosomoides polygyrus Dujardin in mice than the natural product PF1022A. In particular an improved efficacy against Haemonchus contortus Rudolphi and Trichostrongylus colubriformis Giles in sheep compared to the potent cyclic octadepsipeptide PF1022A and its mono-thionated derivative has been observed. Here we report on a specific modification at the N-methyl amide linkage by using the mono-thionated PF1022A, resulting in novel anthelmintically active backbone analogues of PF 1022A.
authors.affiliation: Bayer AG, Bayer CropScience, Research Global Chemistry Insecticides, Alfred-Nobel-Str 50, D-40789 Monheim, Germany. peter.jeschke@bayer-cropscience.com
authors.forename: Peter
authors.initials: P
authors.lastname: Jeschke
authors.forename: Achim
authors.initials: A
authors.lastname: Harder
authors.forename: Georg
authors.initials: G
authors.lastname: von Samson-Himmelstjerna
authors.forename: Winfried
authors.initials: W
authors.lastname: Etzel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gau
authors.forename: Gerhard
authors.initials: G
authors.lastname: Thielking
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bonse
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity*; D047630:Depsipeptides; D006189:Haemonchus / Q000187:drug effects; D006374:Helminthiasis, Animal / Q000188:drug therapy; D006926:Hymenolepis / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008956:Models, Chemical; D009348:Nematoda / Q000187:drug effects*; D009351:Nematospiroides dubius / Q000187:drug effects; D009559:Nippostrongylus / Q000187:drug effects; D010091:Oximes / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism*; D012756:Sheep / Q000469:parasitology; D013329:Structure-Activity Relationship; D014234:Trichinella / Q000187:drug effects; D014254:Trichostrongylus / Q000187:drug effects
chemical_list: D000871:Anthelmintics; D047630:Depsipeptides; D010091:Oximes; D010456:Peptides, Cyclic; C075544:PF 1022A