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 Chemjournal_title
Bioorganic & medicinal chemistryauthors
Conole D,Beck TM,Jay-Smith M,Tingle MD,Eason CT,Brimble MA,Rennison Ddoi
10.1016/j.bmc.2014.02.013subject
Has Abstractpub_date
2014-04-01 00:00:00pages
2220-35issue
7eissn
0968-0896issn
1464-3391pii
S0968-0896(14)00119-9journal_volume
22pub_type
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