145013-05-4

Usage

Uses

Used in Pharmaceutical Industry:
N,N'-BIS-TERT-BUTOXYCARBONYLTHIOUREA is used as a thioacylating agent for the preparation of thiocarbonyl compounds, which are essential in the synthesis of various pharmaceuticals.
Used in Organic Chemistry:
N,N'-BIS-TERT-BUTOXYCARBONYLTHIOUREA is used as a guanylating agent for the synthesis of guanidines, which are important building blocks in organic chemistry and have applications in the development of various chemical compounds.
Used in Medicinal Chemistry:
N,N''-Di(tert-butoxycarbonyl)thiourea is used in the preparation of bis-imidazoline diphenyl derivatives, which serve as α1-adrenoceptor antagonists. These antagonists have potential applications in the treatment of various medical conditions, such as hypertension and benign prostatic hyperplasia.

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 17356-08-0 thiourea 
• 34619-03-9 tert-butyldicarbonate 

Downstream Products

• 145013-08-7 C₂₆H₄₀N₄O₈ 
• 145013-07-6 C₂₅H₃₈N₄O₈ 
• 153114-32-0 N,N′-bis(tert-butoxycarbonyl)-N′′-(2-chlorophenyl)guanidine 
• 145013-06-5 C₁₈H₂₇N₃O₄ 
• 176755-29-6 C₅₄H₆₉Cl₂N₉O₁₂ 
• 175721-64-9 (3R,4S,5S,6S)-6-acetamido-4-(N,N'-bis(tert-butoxycarbonyl)quanidino)-1-N-(tert-butoxycarbonyl)-5-hydroxy-3-[(diphenylmethoxy)carbonyl]piperidine 
• 41651-87-0 p-guanidinomethyl benzoic acid 
• 191530-53-7 (3R,4S,5S,6S)-6-[(benzyloxycarbonyl)amino]-1-N-(tert-butoxycarbonyl)-4-(N,N'-bis(tert-butoxycarbonyl)guanidino)-5-hydroxy-3-[(diphenylmethoxy)carbonyl]piperidine 
• 190447-74-6 C₃₁H₄₆N₆O₁₀ 
• 152120-56-4 N,N′-bis(tert-butoxycarbonyl)-N′′-phenylguanidine 
• 145013-06-5 N,N′-bis(tert-butoxycarbonyl)-N′′-benzylguanidine 
• 183430-93-5 ethyl 3-amino-5-({[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl}amino)benzoate 

Relevant academic research and scientific papers

Preparation of N,N'-bis-tert-butoxycarbonylthiourea

The preparation of N,N'-bis-tert-butoxycarbonylthiourea from thiourea and di-tert-butyl dicarbonate in tetrahydrofuran is described.

Preparation of N-tert-butoxycarbonylthiourea opens the way to protected 2-aminothiazoles

The preparation of N-tert-butoxycarbonylthiourea from thiourea and di-tert-butyldicarbonate in tetrahydrofuran is described. It has been successfully used for the preparation of 2-aminothiazole intermediates.

Di-aryl guanidinium derivatives: Towards improved α2-Adrenergic affinity and antagonist activity

Compounds with excellent receptor engagement displaying α2-AR antagonist activity are useful not only for therapeutic purposes (e.g. antidepressants), but also to help in the crystallization of this particular GPCR. Therefore, based on our broad experience in the topic, we have prepared eighteen di-aryl (phenyl and/or pyridin-2-yl) mono- or di-substituted guanidines and 2-aminoimidazolines. The in vitro α2-AR binding affinity experiments in human brain tissue showed the advantage of a 2-aminoimidazolinium cation, a di-arylmethylene core, a conformationally locked pyridin-2-yl-guanidine and a di-substituted guanidinium to achieve good α2-AR engagement. After different in vitro [35S]GTPγS binding experiments in human prefrontal cortex tissue, it was possible to identify that compounds 7a, 7b and 7c were α2-AR partial agonist, whereas 8h was a potent α2-AR antagonist. Docking and MD studies with a model of α2A-AR and two crystal structures suggest that antagonism is achieved by compounds carrying a di-substituted guanidine which substituent occupy a pocket adjacent to TM5 without engaging S2005.42 or S2045.46, and a mono-substituted cationic group, which favorably interacts with E942.65.

ANTI-INFLAMMATORY DRUG AND USES THEREOF

An anti-inflammatory drug containing a G0/G1 switch 2 (G0S2) inhibitor as an active ingredient is useful as a novel anti-inflammatory drug.

α-Amino Acid-Isosteric α-Amino Tetrazoles

The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α-amino acid-isosteric α-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field.

Neuraminic acid inhibitor prodrug composition and use thereof

Provided are a compound as represented by formula Ia, or pharmaceutically acceptable salt, solvate, polymorph, enantiomer or racemic mixture thereof. As a neuraminidase inhibitor prodrug, the compound can improve the half-life in vivo of the neuraminidase inhibitor. Also provided are a preparation method of the compound, pharmaceutical composition containing the compound, and uses of the compound and the pharmaceutical composition in the preparation of neuraminidase inhibitor drugs for treating related diseases.

INHIBITORS OF BETA-SECRETASE

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the β-secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates.

Copper(II) chloride promoted transformation of amines into guanidines and asymmetrical N,N'-disubstituted guanidines

We present a concise, less-toxic and broadly applicable method for coupling weakly nucleophilic amines with N,N'-di-(tert-butoxycarbonyl)thiourea, N-(tert-butxoycarbonyl), N'-alkyl/arylsubstituted-thioureas and N,N'-di-(tert-butoxycarbonyl)imidazolidine-2-thione in the presence of copper(II) chloride. Subsequent removal of Boc protecting groups affords guanidines, di-substituted guanidines and 2-aminoimidazolines in modest to excellent overall yields.

Proline editing: A general and practical approach to the synthesis of functionally and structurally diverse peptides. Analysis of steric versus stereoelectronic effects of 4-substituted prolines on conformation within peptides

Functionalized proline residues have diverse applications. Herein we describe a practical approach, proline editing, for the synthesis of peptides with stereospecifically modified proline residues. Peptides are synthesized by standard solid-phase peptide synthesis to incorporate Fmoc-hydroxyproline (4R-Hyp). In an automated manner, the Hyp hydroxyl is protected and the remainder of the peptide synthesized. After peptide synthesis, the Hyp protecting group is orthogonally removed and Hyp selectively modified to generate substituted proline amino acids, with the peptide main chain functioning to "protect" the proline amino and carboxyl groups. In a model tetrapeptide (Ac-TYPN-NH2), 4R-Hyp was stereospecifically converted to 122 different 4-substituted prolyl amino acids, with 4R or 4S stereochemistry, via Mitsunobu, oxidation, reduction, acylation, and substitution reactions. 4-Substituted prolines synthesized via proline editing include incorporated structured amino acid mimetics (Cys, Asp/Glu, Phe, Lys, Arg, pSer/pThr), recognition motifs (biotin, RGD), electron-withdrawing groups to induce stereoelectronic effects (fluoro, nitrobenzoate), handles for heteronuclear NMR (19F:fluoro; pentafluorophenyl or perfluoro-tert-butyl ether; 4,4-difluoro; 77SePh) and other spectroscopies (fluorescence, IR: cyanophenyl ether), leaving groups (sulfonate, halide, NHS, bromoacetate), and other reactive handles (amine, thiol, thioester, ketone, hydroxylamine, maleimide, acrylate, azide, alkene, alkyne, aryl halide, tetrazine, 1,2-aminothiol). Proline editing provides access to these proline derivatives with no solution-phase synthesis. All peptides were analyzed by NMR to identify stereoelectronic and steric effects on conformation. Proline derivatives were synthesized to permit bioorthogonal conjugation reactions, including azide-alkyne, tetrazine-trans-cyclooctene, oxime, reductive amination, native chemical ligation, Suzuki, Sonogashira, cross-metathesis, and Diels-Alder reactions. These proline derivatives allowed three parallel bioorthogonal reactions to be conducted in one solution.

Chemical insight into the emergence of influenza virus strains that are resistant to Relenza

A reagent panel containing ten 4-substituted 4-nitrophenyl α-d-sialosides and a second panel of the corresponding sialic acid glycals were synthesized and used to probe the inhibition mechanism for two neuraminidases, the N2 enzyme from influenza type A virus and the enzyme from Micromonospora viridifaciens. For the viral enzyme the logarithm of the inhibition constant (Ki) correlated with neither the logarithm of the catalytic efficiency (kcat/Km) nor catalytic proficiency (kcat/Kmkun). These linear free energy relationship data support the notion that these inhibitors, which include the therapeutic agent Relenza, are not transition state mimics for the enzyme-catalyzed hydrolysis reaction. Moreover, for the influenza enzyme, a correlation (slope, 0.80 ± 0.08) is observed between the logarithms of the inhibition (Ki) and Michaelis (Km) constants. We conclude that the free energy for Relenza binding to the influenza enzyme mimics the enzyme-substrate interactions at the Michaelis complex. Thus, an influenza mutational response to a 4-substituted sialic acid glycal inhibitor can weaken the interactions between the inhibitor and the viral neuraminidase without a concomitant decrease in free energy of binding for the substrate at the enzyme-catalyzed hydrolysis transition state. The current findings make it clear that new structural motifs and/or substitution patterns need to be developed in the search for a bona fide influenza viral neuraminidase transition state analogue inhibitor.