Structure-activity studies on a potent antagonist to organophosphate-induced toxicity.
Molecular modifications have been made on a highly potent, active antagonist to organophosphate-induced toxicity, 4,4'-bis[1,3-dioxan-2-ylmethyl)methylamino]acetyl]biphenyl dimethobromide (1). Stepwise removal of the oxygen atoms from the dioxane rings, as well as changing the position of attachment of substituents on the 1,3-dioxane rings and decreasing the ring size from six-membered to five-membered caused drastic or complete loss of pharmacological effect. Partial structures of 1 were all inactive. Thus, the structure of 1 seems to be remarkably specific. Additional pharmacological data are reported for 1.
Cannon
J G
JG
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242.
Sahin
M F
MF
Bhatnagar
R K
RK
Flynn
J R
JR
Long
J P
JP
D000818:Animals; D002801:Cholinesterase Reactivators / Q000138:chemical synthesis* / Q000494:pharmacology; D006426:Hemicholinium 3 / Q000031:analogs & derivatives; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010261:Paraoxon / Q000037:antagonists & inhibitors* / Q000633:toxicity; D013329:Structure-Activity Relationship
D002801:Cholinesterase Reactivators; D006426:Hemicholinium 3; D010261:Paraoxon