Debenzylation of 2,6,8,12-tetraacetyl-4,10-dibenzyl-2,4,6,8,10,12-hexaazatetracyclo[5.5.0.03,11.05,9]dodecane

Калашников, А. И.; Sysolyatin, S. V.; Сакович, Г. В.; Surmacheva, I. A.; Surmachev, V. N.; Lapina, Yu. T.

doi:10.1007/s11172-009-0295-9

Cited by 9 publications

(3 citation statements)

References 2 publications

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“…Synthetic methods for tetraacetyl hexaazaisowurtzitane ( III ) are commonly known and industrially employed. − A cascade condensation of benzylamine with glyoxal furnished hexabenzyl hexaazaisowurtzitane ( V ). Two-stage hydrogenation of V over the Pd catalyst produced VI (Scheme ).…”

Section: Results and Discussionmentioning

confidence: 99%

Discovery of a Novel Non-Narcotic Analgesic Derived from the CL-20 Explosive: Synthesis, Pharmacology, and Target Identification of Thiowurtzine, a Potent Inhibitor of the Opioid Receptors and the Ion Channels

et al. 2021

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The number of candidate molecules for new non-narcotic analgesics is extremely limited. Here, we report the identification of thiowurtzine, a new potent analgesic molecule with promising application in chronic pain treatment. We describe the chemical synthesis of this unique compound derived from the hexaazaisowurtzitane (CL-20) explosive molecule. Then, we use animal experiments to assess its analgesic activity in vivo upon chemical, thermal, and mechanical exposures, compared to the effect of several reference drugs. Finally, we investigate the potential receptors of thiowurtzine in order to better understand its complex mechanism of action. We use docking, molecular modeling, and molecular dynamics simulations to identify and characterize the potential targets of the drug and confirm the results of the animal experiments. Our findings finally indicate that thiowurtzine may have a complex mechanism of action by essentially targeting the mu opioid receptor, the TRPA1 ion channel, and the Ca v voltage-gated calcium channel.

show abstract

Section: Results and Discussionmentioning

confidence: 99%

Discovery of a Novel Non-Narcotic Analgesic Derived from the CL-20 Explosive: Synthesis, Pharmacology, and Target Identification of Thiowurtzine, a Potent Inhibitor of the Opioid Receptors and the Ion Channels

et al. 2021

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“…Synthetic methods for tetraacetyl hexaazaisowurtzitane ( III ) are commonly known and industrially employed. 23 24 25 A cascade condensation of benzylamine with glyoxal furnished hexabenzyl hexaazaisowurtzitane ( V ). A twostage hydrogenation of V over Pd catalyst produced VI (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Discovery of a Novel Non-Narcotic Analgesic Derived from the CL-20 Explosive: Synthesis, Pharmacology and Target Identification of Thio-wurtzine, a Potent Inhibitor of the Opioid Receptors and the Voltage-Dependent Calcium Channels

Aguero

Mégy

Fournier

et al. 2021

Preprint

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The number of candidate molecules for new non-narcotic analgesics is extremely limited. Here we report the identification of thiowurtzine, a new potent analgesic molecule with promising application in chronic pain treatment. We describe the chemical synthesis of this unique compound derived from the hexaazaisowurtzitane (CL-20) explosive molecule. Then we use animal experiments to assess its analgesic activity in vivo upon chemical, thermal and mechanical exposures, compared to the effect of several reference drugs. Finally, we investigate the potential receptors of thiowurtzine in order to better understand its complex mechanism of action. We use docking, molecular modeling and molecular dynamics simulations to identify and characterize the potential targets of the drug and confirm the results of the animal experiments. Our findings finally indicate that thiowurtzine may have a complex mechanism of action, by targeting the mu, kappa, delta and ORL1 opioid receptors, and the voltage-gated calcium channels as well.

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“…In order to eliminate the step of isolation of crystalline TADB from the solution in acetic acid, conduction of the second debenzylation step in a mixture of formic and acetic acids was proposed. 626 A TEM study of catalyst samples demonstrated that in the repeated use of the catalyst, palladium particle size considerably increases and, hence, the active metal surface area decreases. The coarsening of palladium particles in both the first and second debenzylation steps occurs from one cycle to another to reach a definite threshold value after which the catalyst completely loses activity.…”

Section: Scheme 149mentioning

confidence: 99%

Development of new methods in modern selective organic synthesis: preparation of functionalized molecules with atomic precision

Ananikov¹,

Khemchyan²,

Іvanova³

et al. 2014

Russ. Chem. Rev.

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Debenzylation of 2,6,8,12-tetraacetyl-4,10-dibenzyl-2,4,6,8,10,12-hexaazatetracyclo[5.5.0.03,11.05,9]dodecane

Cited by 9 publications

References 2 publications

Discovery of a Novel Non-Narcotic Analgesic Derived from the CL-20 Explosive: Synthesis, Pharmacology, and Target Identification of Thiowurtzine, a Potent Inhibitor of the Opioid Receptors and the Ion Channels

Discovery of a Novel Non-Narcotic Analgesic Derived from the CL-20 Explosive: Synthesis, Pharmacology, and Target Identification of Thiowurtzine, a Potent Inhibitor of the Opioid Receptors and the Ion Channels

Discovery of a Novel Non-Narcotic Analgesic Derived from the CL-20 Explosive: Synthesis, Pharmacology and Target Identification of Thio-wurtzine, a Potent Inhibitor of the Opioid Receptors and the Voltage-Dependent Calcium Channels

Development of new methods in modern selective organic synthesis: preparation of functionalized molecules with atomic precision

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