21075-83-2

Usage

Uses

Used in Pharmaceutical Industry:
METHYL TERT BUTYL CARBAZATE OR CEP 11841 is used as a reactant for the synthesis of the hydrazide of (2S,3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane, which is the lead structure of the irreversible cathepsin C inhibitor. This application is significant because it contributes to the development of new drugs that can potentially treat various medical conditions by targeting specific enzymes or proteins in the body.

Upstream product

• 29518-83-0 S-Methyl-monothiokohlensaeure-tert.-butylester 
• 60-34-4 methylhydrazine 
• 16965-08-5 1,1-dimethylethyl 2,4,5-trichlorophenyl carbonate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 691-64-5 di-tert-butyl oxalate 
• 302-15-8 methylhydrazine sulfuric acid 
• 220294-77-9 N^β,N^β-[bis(tert-butoxycarbonyl)amino]phthalimide 
• 215655-64-4 1-tert-butyloxycarbonyl-2-(2'-carboxybenzoyl)-hydrazine 
• 109473-36-1 N-tert-butyloxycarbonylaminoisophthalimide 
• 870-46-2 t-butoxycarbonylhydrazine 
• 34387-89-8 N-(tert-butoxycarbonylamino)phthalimide 
• 287728-99-8 tert-butyl (1,3-dioxoisoindolin-2-yl)(methyl)carbamate 

Downstream Products

• 58647-44-2 4-Benzyl-1-(tert.-butoxycarbonyl)-1-methyl-thiosemicarbazid 
• 21076-00-6 1-tert.-Butoxycarbonyl-1-methyl-4-phenyl-thiosemicarbazid 
• 58647-46-4 1-(tert.-Butoxycarbonyl)-1-methyl-4-(2,6-dimethyl-phenyl)-thiosemicarbazid 
• 74-93-1 methylthiol 
• 83274-34-4 N²-tert-Butoxycarbonyl-N²-methylbenzamidrazoniumiodid 
• 150650-87-6 1-(N-benzyloxycarbonyl-L-tyrosyl)-2-methyl-2-tert-butoxycarbonyl hydrazine 
• 150650-88-7 1-(N-benzyloxycarbonyl-3-iodo-L-tyrosyl)-2-methyl-2-tert-butoxycarbonyl hydrazine 
• 113220-18-1 (Z)-3-(N'-Methyl-hydrazino)-2-(2,3,4,5-tetrafluoro-benzoyl)-acrylic acid ethyl ester 
• 65806-35-1 1-(N-Benzyloxycarbonyl-O-benzyl-L-tyrosyl)-2-t-butoxycarbonyl-2-methyl-hydrazid 
• 485831-43-4 N'-(2-benzyloxycarbonylamino-3-hydroxy-propionyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester 
• 959658-40-3 N-Boc-N-methyl-N'-benzylcarbamoyl-hydrazine 

Relevant academic research and scientific papers

Design, Synthesis, and Characterization of Cyclic Peptidomimetics of the Inducible Nitric Oxide Synthase Binding Epitope That Disrupt the Protein-Protein Interaction Involving SPRY Domain-Containing Suppressor of Cytokine Signaling Box Protein (SPSB) 2 and Inducible Nitric Oxide Synthase

SPRY domain-containing suppressor of cytokine signaling box protein (SPSB) 2-deficient macrophages have been found to exhibit prolonged expression of inducible nitric oxide synthase (iNOS) and enhanced killing of persistent pathogens, suggesting that inhibitors of the SPSB2-iNOS interaction have potential as novel anti-infectives. In this study, we describe the design, synthesis, and characterization of cyclic peptidomimetic inhibitors of the SPSB2-iNOS interaction constrained by organic linkers to improve stability and druggability. SPR, ITC, and 19F NMR analyses revealed that the most potent cyclic peptidomimetic bound to the iNOS binding site of SPSB2 with low nanomolar affinity (KD 29 nM), a 10-fold improvement over that of the linear peptide DINNN (KD 318 nM), and showed strong inhibition of SPSB2-iNOS interaction in macrophage cell lysates. This study exemplifies a novel approach to cyclize a Type II β-turn linear peptide and provides a foundation for future development of this group of inhibitors as new anti-infectives.

3-Cyano-3-aza-β-amino acid derivatives as inhibitors of human cysteine cathepsins

Nitrile-type inhibitors are known to interact with cysteine proteases in a covalent-reversible manner. The chemotype of 3-cyano-3-aza-β-amino acid derivatives was designed in which the N-cyano group is centrally arranged in the molecule to allow for interactions with the nonprimed and primed binding regions of the target enzymes. These compounds were evaluated as inhibitors of the human cysteine cathepsins K, S, B, and L. They exhibited slow-binding behavior and were found to be exceptionally potent, in particular toward cathepsin K, with second-order rate constants up to 52 900 × 103M-1s-1.

WEE1 KINASE INHIBITORS AND METHODS OF TREATING CANCER USING THE SAME

A compound, or a pharmaceutically acceptable salts or prodrugs thereof, having the chemical structure (I) and methods of using these compounds to inhibit WEE1 kinase and treat cancer in a subject.

Development of Potent Pyrazolopyrimidinone-Based WEE1 Inhibitors with Limited Single-Agent Cytotoxicity for Cancer Therapy

WEE1 kinase regulates the G2/M cell-cycle checkpoint, a critical mechanism for DNA repair in cancer cells that can confer resistance to DNA-damaging agents. We previously reported a series of pyrazolopyrimidinones based on AZD1775, a known WEE1 inhibitor, as an initial investigation into the structural requirements for WEE1 inhibition. Our lead inhibitor demonstrated WEE1 inhibition in the same nanomolar range as AZD1775, and potentiated the effects of cisplatin in medulloblastoma cells, but had reduced single-agent cytotoxicity. These results prompted the development of a more comprehensive series of WEE1 inhibitors. Herein we report a series of pyrazolopyrimidinones and identify a more potent WEE1 inhibitor than AZD1775 and additional compounds that demonstrate that WEE1 inhibition can be achieved with reduced single-agent cytotoxicity. These studies support that WEE1 inhibition can be uncoupled from the potent cytotoxic effects observed with AZD1775, and this may have important ramifications in the clinical setting where WEE1 inhibitors are used as chemosensitizers for DNA-targeted chemotherapy.

Synthetic method of Fmoc-Aza-beta 3-Ala

The invention discloses a synthetic method of Fmoc-Aza-Beta 3-Ala. The method comprises the following steps: processing methylhydrazine by utilizing excessive di-tert-butyl dicarbonate ester to obtaina compound 1 as shown in formula B1, Fmoc-cl and NaHCO3 are added into the compound 1 shown in the formula B1 to have nucleophilic substitution to obtain a compound 2 as shown in formula B2, the compound 2 as shown in the formula B2 is obtained by virtue of the acidification of trifluoroacetic acid (TFA) or HCLG, so that a Boc protection group is broken to obtain a compound 3 as shown in formulaB3; the compound 3 as shown in the formula B3 is enable to have nucleophilic substitution with tert-butyl bromoacetate to obtain a compound 4 as shown in formula A4; and the compound 4 as shown in theformula A4 is enabled to have degreasing reaction with dichloromethane introduced with HCl gas to obtain a target product Fmoc-Aza-Beta 3-Ala as shown in formula B5. The preparation method provided by the invention is mild in reaction condition, the Fmoc protection group can be easily removed by utilizing a mild alkaline condition, the operation is simple, the acid instable group can be used forprotecting a side chain, and a route is simple and efficient.

Preparation method of anamorelin intermediate

The invention relates to the field of medicine synthesis, in particular to a preparation method of an anamorelin intermediate. On one hand, 1-boc-1-methylhydrazine is taken as a reaction material, anda key intermediate tert-butyl N,N',N'-trimethylhydrazinecarboxylate is prepared in one pot with a formaldehyde compound and palladium catalyst/hydrogen source alternative reaction method. The methodis simple to operate, and the used raw material is safe and easy to obtain; compared with the prior art, the method has the increased yield; on the other hand, in the method, tert-butyl N,N',N'-trimethylhydrazinecarboxylate and hydrochloric acid are subjected to a reaction in an organic solvent, and a high-yield and high-purity crystallized product of N,N',N'-trimethylhydrazine hydrochloride can be directly obtained, and the crystallized product is not required to be further purified and is low in moisture absorption, convenient to store and very suitable for industrial mass production.

N -aminopyridinium salts as precursors for N-centered radicals - Direct amidation of arenes and heteroarenes

Readily prepared N-aminopyridinium salts are valuable precursors for the generation of N-centered radicals. Reduction of these salts by single electron transfer allows for clean generation of amidyl radicals. It is shown that direct radical C-H amination of heteroarenes and arenes can be achieved with N-aminopyridinium salts under mild conditions by using photoredox catalysis.

Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs

Optimization of a new series of S-adenosyl-l-homocysteine hydrolase (AdoHcyase) inhibitors based on non-adenosine analogs led to very potent compounds 14n, 18a, and 18b with IC50 values of 13 ± 3, 5.0 ± 2.0, and 8.5 ± 3.1 nM, respectively. An X-ray crystal structure of AdoHcyase with NAD+ and 18a showed a novel open form co-crystal structure. 18a in the co-crystals formed intramolecular eight membered ring hydrogen bond formations. A single crystal X-ray structure of 14n also showed an intramolecular eight-membered ring hydrogen bond interaction.

Design and synthesis of 5-[(2-chloro-6-fluorophenyl)acetylamino]-3-(4- fluorophenyl)-4-(4-pyrimidinyl)isoxazole (AKP-001), a novel inhibitor of p38 MAP kinase with reduced side effects based on the antedrug concept

Inhibitors of p38 mitogen-activated protein (MAP) kinase, which are closely involved in the production of inflammatory cytokines, are considered promising curative drugs for chronic inflammatory disorders. However, there is also a growing concern regarding its systemic side effects. To reduce the occurrence of side effects, we have identified a novel p38 MAP kinase inhibitor that shows properties of an antedrug, which imparts its effect solely on the inflammatory site and is metabolically inactivated right after. We have designed isoxazole derivatives through the addition of a fresh interacting fourth site to the structure of the prototypical p38 MAP kinase inhibitor that harbors three point interactive sites. The derivative 26d (AKP-001) shows excellent p38 MAP kinase inhibitory activity and a high selectivity for various kinases. Its rapid metabolism has been confirmed in rats. Moreover, 26d has been shown to be effective in animal models of inflammatory bowel disease.

Stereodynamics of nitrogen chiral centers in aza-β3- cyclodipeptides

The present work is devoted to the synthesis, conformational analysis, and stereodynamic study of aza-β3-cyclodipeptides. This pseudopeptidic ring shows E/Z hydrazide bond isomerism, eight-membered ring conformation, and chirotopic nitrogen atoms, all of which are elements that are prone to modulate the ring shape. The (E,E) twist boat conformation observed in the solid state by X-ray diffraction is also the ground conformation in solution, and emerges as the lowest in energy when using quantum chemical calculations. The relative configuration associated with ring chirality and with the two nitrogen chiral centers is governed by steric crowding and adopts the (P)SNSN/(M)RNRN combination which projects side chains in equatorial position. The nitrogen pyramidal inversion (NPI) at the two chiral centers is correlated with the ring reversal. The process is significantly hindered as was shown by VT-NMR experiments run in C2D2Cl4, which did not make it possible to determine the barrier to inversion. Finally, these findings make it conceivable to resolve enantiomers of aza-β3-cyclodipeptides by modulating the backbone decoration appropriately.