The Action of Ammonia and Amines on the Substituted Ureas and Urethanes. Ii. Allophanic Ester.

Dains, F. B.; Wertheim, E.

doi:10.1021/ja01456a023

Cited by 33 publications

(21 citation statements)

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“…[20] 1,2-Diphenylurazole was obtained by condensation of 1,2-diphenylhydrazine and ethyl allophanate, which was prepared from urea and ethyl chloroformate. [21] For the synthesis of building block 6, [19] anthraquinone was converted into 5H-dibenzo[b,e]azepine-6,11-dione (3) by Schmidt reaction (Scheme 2). The resulting ketone was reduced to the alcohol 4 by sodium borohydride in ethanol at reflux.…”

Section: Synthesismentioning

confidence: 99%

Application of the Guanidine–Acylguanidine Bioisosteric Approach to Argininamide‐Type NPY Y₂ Receptor Antagonists

et al. 2011

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Strongly basic groups such as guanidine moieties are crucial structural elements, but they compromise the drug-likeness of numerous biologically active compounds, including ligands of G-protein-coupled receptors (GPCRs). As part of a project focused on the search for guanidine bioisosteres, argininamide-type neuropeptide Y (NPY) Y₂ receptor (Y₂R) antagonists related to BIIE0246 were synthesized. Starting from ornithine derivatives, N(G) -acylated argininamides were obtained by guanidinylation with tailor-made mono-Boc-protected N-acyl-S-methylisothioureas. The compounds were investigated for Y₂R antagonism (calcium assays), Y₂R affinity, and NPY receptor subtype selectivity (flow cytometric binding assays). Most of the N(G) -substituted (S)-argininamides showed Y₂R antagonistic activities and binding affinities similar to those of the parent compound, whereas N(G)-acylated or -carbamoylated analogues with a terminal amine were superior (Y₂R: K(i) and K(B) values in the low nanomolar range). This demonstrates that the basicity of the compounds, although 4-5 orders of magnitude lower than that of guanidines, is sufficient to form key interactions with acidic amino acids of the Y₂R. The acylguanidines bind with high affinity and selectivity to Y₂R over the Y₁, Y₄, and Y₅ receptors. As derivatization of the amino group is tolerated, these compounds can be considered building blocks for the preparation of versatile fluorescent and radiolabeled pharmacological tools for in vitro studies of the Y₂R. The results support the concept of bioisosteric guanidine-acylguanidine exchange as a broadly applicable approach to retain pharmacological activity despite decreased basicity.

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Section: Synthesismentioning

confidence: 99%

Application of the Guanidine–Acylguanidine Bioisosteric Approach to Argininamide‐Type NPY Y₂ Receptor Antagonists

et al. 2011

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“…The thermal cyclization of 1-phenyl-4-carbethoxysemicarbazide has been shown to result in the formation of 1-phenyl-1,2,4-triazolidine-3,5-dione [1]. The nucleophilic addition of Lewis bases with carboisocyanatidic acid ethyl ester (1) is well known since 1908 [2].…”

Section: Introductionmentioning

confidence: 99%

“…In former work we have described the multistage preparation of [1,2,4]triazolo[1,2-a][1,2,4]triazole-1,3,5,7-tetraone 8 [5]. In the reaction of 1,2,4-triazole-3,5-dione (6) with 1, a quantitative yield of (3,5-dioxo [1,2,4]triazolidine-1-carbonyl)-carbamic acid ethyl ester (7) is obtained.…”

Section: Introductionmentioning

confidence: 99%

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An Easy Access to Hydrazinocarbonyl Carbamic Acid Ethyl Esters

Faleschini

1999

Monatshefte fuer Chemie

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“…The latter's argument was not rigorous enough to solve the problem of Pinner's "phenylurazole" structure. There is also some doubt about the structure of the "phenylurazole" of Dains (11). The controversy on whether Pinner's "phenylurazole" and "diphenylurazine" are sym-tetrazines or 1,2,4-triazoles has now been settled in this laboratory by 13C n.m.r.…”

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confidence: 99%

Hydrazine Derivatives. I. Transcarbamylation Reaction

Lenoir¹,

Colebrook²,

Williams³

1972

Can. J. Chem.

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Improvements in the synthesis of urazoles via a proposed transcarbamylation reaction are reported. Some experimental evidence for a transcarbamylation mechanism as indicated by the formation of identified intermediate products is shown. 13C n.m.r. studies on I-phenyl-4-anilinourazole have settled the controversy on the structure of Pinner's compounds by establishing that they are 1,2,4-triazoles rather than sym-tetrazines.Amelioration dessynthesesdes urazoles au moyen deconditions favorablesaux reactionsde transcarbamylation. L'identification de quelques produits intermediaires favorise le postulat d'un mecanisme de transcarbamylation. La controverse sur la structure des tetrazines symmetriques et triazoles-1,2,4 est definitivement reglee. Les etudes de r.m.n. basees sur le CI3 Btablissent clairement la nature des produits de Pinner.

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The Action of Ammonia and Amines on the Substituted Ureas and Urethanes. Ii. Allophanic Ester.

Cited by 33 publications

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Application of the Guanidine–Acylguanidine Bioisosteric Approach to Argininamide‐Type NPY Y₂ Receptor Antagonists

Application of the Guanidine–Acylguanidine Bioisosteric Approach to Argininamide‐Type NPY Y₂ Receptor Antagonists

An Easy Access to Hydrazinocarbonyl Carbamic Acid Ethyl Esters

Hydrazine Derivatives. I. Transcarbamylation Reaction

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The Action of Ammonia and Amines on the Substituted Ureas and Urethanes. Ii. Allophanic Ester.

Cited by 33 publications

References 0 publications

Application of the Guanidine–Acylguanidine Bioisosteric Approach to Argininamide‐Type NPY Y2 Receptor Antagonists

Application of the Guanidine–Acylguanidine Bioisosteric Approach to Argininamide‐Type NPY Y2 Receptor Antagonists

An Easy Access to Hydrazinocarbonyl Carbamic Acid Ethyl Esters

Hydrazine Derivatives. I. Transcarbamylation Reaction

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Application of the Guanidine–Acylguanidine Bioisosteric Approach to Argininamide‐Type NPY Y₂ Receptor Antagonists

Application of the Guanidine–Acylguanidine Bioisosteric Approach to Argininamide‐Type NPY Y₂ Receptor Antagonists