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

Conole, Daniel; Beck, Thorsten M.; Jay-Smith, Morgan; Tingle, Malcolm D.; Eason, Charles; Brimble, Margaret A.; Rennison, David

doi:10.1016/j.bmc.2014.02.013

Cited by 28 publications

(23 citation statements)

References 71 publications

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“…These benzaldehyde derivatives (5a–d ) converted to their respective nitriles (4a–d) upon heating with hydroxylamine hydrochloride in DMSO at 100 °C for 3 h . Further reflux of nitrile (4a–d) with hydroxylamine hydrochloride in ethanol led to benzamidoxime intermediates (3a–d) , which on further refluxing with 1,4‐ or 1,3‐benzene dicarboxylic acid chlorides in pyridine afforded p ‐substituted polycatenars (1a, 1p/n) and m ‐substituted polycatenars (2a, 2m/n) . The structures of all the intermediates and target molecules were confirmed using 1 H NMR, 13 C NMR, IR spectroscopy and ESI‐HRMS or MALDI‐TOF analysis.…”

Section: Resultsmentioning

confidence: 96%

Hexacatenars Exhibiting π-π Driven Supergelation, Aggregation Induced Blue Light Emission and Thermochromism

et al. 2016

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Two series of five ring polycatenars, which vary from each other with respect to the position of connection to the central benzene ring are reported. The overall shape of the molecule plays a major role than the number of flexible tails in the periphery in dictating the self-assembly (liquid crystallinity and gelation) and the photophysical behavior. Tetracatenars were crystalline and meta-substituted compounds exhibited reduced tendency to stabilize the mesophase. In the para-substituted series, all the hexacatenars exhibited columar hexagonal phase. p-Sub-stituted hexacatenar with n-dodecyloxy tails exhibited thermochromism, with the highly emissive Col h phase and non-emissive soft crystal phase. Three p-substituted compounds exhibited supergelation exclusively promoted by p-p interactions. Besides the capability to form self-standing, moldable gel, one of the compounds exhibited technologically important aggregation-induced blue light emission. The columnar order and emissive nature in the aggregated state makes these molecules promising for the application in emissive displays.

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Section: Resultsmentioning

confidence: 96%

Hexacatenars Exhibiting π-π Driven Supergelation, Aggregation Induced Blue Light Emission and Thermochromism

et al. 2016

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“…The first approach is regarded as a tandem reaction: a mixture of amidoxime 5 and carboxylic acid chloride is treated with a base followed by in situ heating of the formed O-acylamidoxime 4 to induce cyclization into 1,2,4oxadiazole, e.g., by heating in a sealed tube at 175 o C in pyridine, 22 26 or Py. 27 The second approach for the construction of 3,5disubstituted 1,2,4-oxadiazole core involves preliminary isolation of the O-acylamidoximes 4 with the subsequent individual cyclization step proceeding in the presence of a condensation reagent. However, almost in all cases, long-term heating is required for the cyclization to proceed, e.g., refluxing in AcOH, 28 in acetone in the presence of K 2 CO 3,29 in dioxane in the presence of KF, 30 or in xylene.…”

Section: Resultsmentioning

confidence: 99%

Efficient assembly of mono- and bis(1,2,4-oxadiazol-3-yl)furoxan scaffolds via tandem reactions of furoxanylamidoximes

2015

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A general, facile, highly effective one-pot protocol for the synthesis of new types of heterocyclic systems incorporating mono-and bis(1,2,4-oxadiazol-3-yl)furoxan cores based on the tandem heterocyclization of furoxanylamidoximes with various aliphatic, aromatic, and heterocyclic carboxylic acid chlorides under very mild conditions (Cs2CO3,MeCN, 20 o C) has been developed. In addition, a solvent-free approach for the (1,2,4-oxadiazol-3-yl)furoxan synthesis by the reaction of furoxanylamidoximes with trimethyl orthoformate catalyzed by Sc(OTf)3 has been achieved. The advantages of step economy and scope make these reactions a powerful tool for assembling heterocyclic scaffolds of general chemistry and biomedical interest.

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“…There is an increasing movement toward the development of oral toxicants whose primary mode of action is through acute methemoglobinemia because this pathway is relatively humane [29][30][31][32][33] . Rapid induction of acute methemoglobinemia induces unconsciousness and death with minimal symptoms of distress.…”

Section: Discussionmentioning

confidence: 99%

Lethal methemoglobinemia in the invasive brown treesnake after acetaminophen ingestion

Mathies

Mauldin

2020

Sci Rep

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the invasive brown treesnake (Boiga irregularis) has extirpated much of Guam's native birdlife and poses significant threats to other parts of the western Pacific. Acetaminophen (APAP) is a proven lethal oral toxicant in reptiles but the physiological mechanism is unknown. The effects of a lethal APAP oral dose on methemoglobin (MetHb, non-oxygen carrying form) levels and other blood parameters were examined in brown treesnakes. Co-oximetry was used to measure MetHb (%) and other hemoglobin species. Assessment of red blood cell integrity, white blood cell differential counts, and plasma biochemical analyses were conducted to evaluate tissue damage, stress, and liver function. Changes in oxygen carrying capacity were noted in APAP-treated snakes indicated by a 50-60% increase in methemoglobin levels and a 40% decrease in oxyhemoglobin (oxygen-carrying form) levels compared to controls. APAP-treated snakes had decreased lymphocyte and increased monocyte counts while also having increased levels of blood analytes associate with impaired liver function and muscle damage. the proximate cause of death in APAP-treated snakes was likely acute methemoglobinemia and respiratory failure due to severe hypoxia with no observed signs of distress or pain. An orally-ingested lethal dose of APAP appears to be a humane method for lethal control of this species.

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

Cited by 28 publications

References 71 publications

Hexacatenars Exhibiting π-π Driven Supergelation, Aggregation Induced Blue Light Emission and Thermochromism

Hexacatenars Exhibiting π-π Driven Supergelation, Aggregation Induced Blue Light Emission and Thermochromism

Efficient assembly of mono- and bis(1,2,4-oxadiazol-3-yl)furoxan scaffolds via tandem reactions of furoxanylamidoximes

Lethal methemoglobinemia in the invasive brown treesnake after acetaminophen ingestion

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