Synthesis and biological activity of anthelmintic thiadiazoles using an AF-2 receptor binding assay.
Following our discovery of the strong binding of thiadiazole 1 to the AF-2 neuropeptide receptor of gastrointestinal nematodes (e.g., Ascaris suum), we prepared two series of analogs. Only the series containing the thiadiazole ring had potencies comparable to that of compound 1. Analog 50 exhibited an apparent potency in the AF-2 binding assay 300 times that of compound 1.
Animal Health Discovery Research, Pharmacia & Upjohn, Inc., Kalamazoo, MI 49001, USA.
B H
BH
Lee
F E
FE
Dutton
M F
MF
Clothier
J W
JW
Bowman
J P
JP
Davis
S S
SS
Johnson
E M
EM
Thomas
M R
MR
Zantello
E W
EW
Zinser
J C
JC
McGuire
D P
DP
Thompson
T G
TG
Geary
D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017165:Ascaris suum; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology; D015801:Helminth Proteins / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000871:Anthelmintics; D015801:Helminth Proteins; D009479:Neuropeptides; D013830:Thiadiazoles; C073964:AF2 neuropeptide