Synthesis of NovelN1-Substituted Bicyclic Pyrazole Amino Acids and Evaluation of Their Interaction with Glutamate Receptors

Conti, Paola; Grazioso, Giovanni; Ventimiglia, Samuele Joppolo di; Pinto, Andrea; Roda, Gabriella; Madsen, Ulf; Bräuner‐Osborne, Hans; Nielsen, Birgitte; Costagli, Chiara; Galli, Alessandro

doi:10.1002/cbdv.200590052

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…Importantly, both pyrazole‐ and CO 2 ‐mediated euthanasia may induce metabolic changes, potentially resulting in changes in lactate or glucose concentrations within the serum or CSF. For example, pyrazole has been demonstrated to inhibit glutamatergic signaling by metabotropic glutamate receptors and impair mitochondrial oxidative phosphorylation and calcium uptake (Cederbaum and Rubin, ; Chae et al., ; Conti et al., ). Similarly, CO 2 exposure prior to death may result in transient respiratory acidosis (Traslavina et al., ).…”

Section: Discussionmentioning

confidence: 99%

Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte–Neuron Lactate Shuttle in the Brain

Lindberg

Peyton

et al. 2019

Alcoholism Clin & Exp Res

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Background: Impairment of monocarboxylate transporter (MCT)-dependent astrocyte-neuron lactate transfer disrupts long-term memory and erases drug-associated memories in mice. However, few studies have examined how drugs of abuse alter astrocyte-neuron lactate transfer in neurocircuits related to addiction. This is particularly pertinent for ethanol (EtOH), which has been demonstrated to impair central nervious system (CNS) glucose uptake and significantly alter peripheral levels of glucose, lactate, acetate, and ketones.Methods: We subjected C57BL/6J mice to a chronic intermittent EtOH (CIE) exposure paradigm to investigate how chronic EtOH exposure alters the concentration of glucose and lactate within the serum and CNS during withdrawal. Next, we determine how chronic injections of lactate (1 g/kg, twice daily for 2 weeks) influence central and peripheral glucose and lactate concentrations. Finally, we determine how CIE and chronic lactate injection affect astrocyte-neuron lactate transfer by analyzing the expression of MCTs.Results: Our results show that CIE induces lasting changes in CNS glucose and lactate concentrations, accompanied by increased expression of MCTs. Interestingly, although chronic lactate injection mimics the effect of EtOH on CNS metabolites, chronic lactate injection is not associated with increased expression of MCTs.Conclusion: CIE increases CNS concentrations of glucose and lactate and augments the expression of MCTs. Although we found that chronic lactate injection mimics EtOH-induced increases in CNS lactate and glucose, lactate failed to alter the expression of MCTs. This suggests that although lactate may influence the homeostasis of bioenergetic molecules in the CNS, EtOH-associated increases in lactate are not responsible for increased MCT expression.

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Section: Discussionmentioning

confidence: 99%

Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte–Neuron Lactate Shuttle in the Brain

Lindberg

Peyton

et al. 2019

Alcoholism Clin & Exp Res

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“…Instead, chlorohydrazone 3d was obtained after the Boc protecting group present in 8d was removed under acidic conditions and the deprotected hydrazonoacetate 10d was chlorinated with N-chlorosuccinimide in analogy with a literature precedent (Scheme 2). 10 Having successfully prepared several (alkylhydrazono)(chloro)acetates 3, we next examined their transformation into the desired 6-aminopyridazin-3(2H)-ones 6 ( Table 1). For example, treatment of 3a with three equivalents of diethylamine at 100°C in 1,4-dioxane for four hours ( 13 After a second basic workup, the crude material thus obtained was briefly exposed to a slight excess of sodium ethoxide in ethanol at 50°C to afford the desired 6-aminopyridazin-3(2H)-one 6a (cf.…”

Section: Methodsmentioning

confidence: 99%

“…We therefore began the development of our new methodology with the preparation of several (alkylhydrazono)(chloro)acetates 3 (R 1 = alkyl). 10…”

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confidence: 99%

Regiospecific Synthesis of Novel 6-Amino-5-hydroxypyridazin-3(2H)-ones

Dragovich¹,

Blazel²,

Dao³

et al. 2008

Synthesis

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The synthesis of a novel class of 6-amino-5-hydroxypyridazin-3(2H)-ones (3-oxo-2,3-dihydropyridazines) is described. These compounds also contain an ethoxycarbonyl moiety at the 4-position of the pyridazinone ring. They are prepared in good to moderate yields (30-72%) by the condensation of disubstituted amines with (alkylhydrazono)-or (arylhydrazono)(chloro)acetates followed by subsequent acylation with ethyl malonyl chloride and Dieckmann cyclization. An initial assessment of the scope and limitations of the new methodology is described along with the novel synthesis of several (alkylhydrazono)(chloro)acetate substrates utilized in the pyridazinone preparations.

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A survey of applications of tetrahydropyrrolo-3,4-azoles and tetrahydropyrrolo-2,3-azoles in medicinal chemistry

Meanwell

Sistla²

2021

Advances in Heterocyclic Chemistry

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Synthesis of NovelN1-Substituted Bicyclic Pyrazole Amino Acids and Evaluation of Their Interaction with Glutamate Receptors

Cited by 4 publications

References 22 publications

Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte–Neuron Lactate Shuttle in the Brain

Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte–Neuron Lactate Shuttle in the Brain

Regiospecific Synthesis of Novel 6-Amino-5-hydroxypyridazin-3(2H)-ones

A survey of applications of tetrahydropyrrolo-3,4-azoles and tetrahydropyrrolo-2,3-azoles in medicinal chemistry

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