Kaleem Ahmed S

References (1)

Title : Synthesis and anti-acetylcholinesterase properties of novel beta- and gamma-substituted alkoxy organophosphonates - Kaleem_2013_Bioorg.Med.Chem.Lett_23_2048
Author(s) : Kaleem Ahmed S , Belabassi Y , Sankaranarayanan L , Chao CK , Gerdes JM , Thompson CM
Ref : Bioorganic & Medicinal Chemistry Lett , 23 :2048 , 2013
Abstract : Activated organophosphate (OP) insecticides and chemical agents inhibit acetylcholinesterase (AChE) to form OP-AChE adducts. Whereas the structure of the OP correlates with the rate of inhibition, the structure of the OP-AChE adduct influences the rate at which post-inhibitory reactivation or aging phenomena occurs. In this report, we prepared a panel of beta-substituted ethoxy and gamma-substituted propoxy phosphonoesters of the type p-NO(2)PhO-P(X)(R)[(O(CH(2))(n)Z] (R=Me, Et; X=O, S; n=2, 3; Z=halogen, OTs) and examined the inhibition of three AChEs by select structures in the panel. The beta-fluoroethoxy methylphosphonate analog (R=Me, Z=F, n=2) was the most potent anti-AChE compound comparable (ki approximately 6 x 10(6)M(-1)min(-1)) to paraoxon against EEAChE. Analogs with Z=Br, I, or OTs were weak inhibitors of the AChEs, and methyl phosphonates (R=Me) were more potent than the corresponding ethyl phosphonates (R=Et). As expected, analogs with a thionate linkage (PS) were poor inhibitors of the AChEs.
ESTHER : Kaleem_2013_Bioorg.Med.Chem.Lett_23_2048
PubMedSearch : Kaleem_2013_Bioorg.Med.Chem.Lett_23_2048
PubMedID: 23453838