Synthesis and methemoglobinemia-inducing properties of benzocaine isosteres designed as humane rodenticides.

Abstract:

:A number of isosteres (oxadiazoles, thiadiazoles, tetrazoles and diazines) of benzocaine were prepared and evaluated for their capacity to induce methemoglobinemia-with a view to their possible application as humane pest control agents. It was found that an optimal lipophilicity for the formation of methemoglobin (metHb) in vitro existed within each series, with 1,2,4-oxadiazole 3 (metHb%=61.0±3.6) and 1,3,4-oxadiazole 10 (metHb%=52.4±0.9) demonstrating the greatest activity. Of the 5 candidates (compounds 3, 10, 11, 13 and 23) evaluated in vivo, failure to induce a lethal end-point at doses of 120mg/kg was observed in all cases. Inadequate metabolic stability, particularly towards hepatic enzymes such as the CYPs, was postulated as one reason for their failure.

journal_name

Bioorg Med Chem

authors

Conole D,Beck TM,Jay-Smith M,Tingle MD,Eason CT,Brimble MA,Rennison D

doi

10.1016/j.bmc.2014.02.013

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

2220-35

issue

7

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(14)00119-9

journal_volume

22

pub_type

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