18684-16-7

Upstream product

• 67-56-1 methanol 
• 71-00-1 L-histidine 
• 71-00-1 L-histidine 
• 645-35-2 L-histidine monohydrochloride 
• 1007-42-7 L-Histidine dihydrochloride 
• 149-73-5 trimethyl orthoformate 
• 1604-44-0 N-α-trifluoroacetyl-L-histidine methyl ester 
• 2488-14-4 N-(tert-butoxycarbonyl)-L-histidine methyl ester 
• 328526-86-9 (R)-histidine monohydrochloride monohydrate 
• 6341-24-8 D-histidine monohydrochloride 
• 351-50-8 D-histidin 
• 30032-32-7 D-histidine ; L_g-tartrate 
• 71-00-1 D-histidine 
• 17791-52-5 (S)-2-tert-Butoxycarbonylamino-3-(3H-imidazol-4-yl)-propionic acid 

Downstream Products

• 3884-02-4 Z-glycyl-glycyl-L-histidine methyl ester 
• 72827-24-8 Z-Val-Tyr(Bu^t)-His-OMe 
• 15545-10-5 Z-His-OMe 
• 37941-52-9 Cbz-Gly-His-OMe 
• 215313-29-4 Dodecanoic acid (2S,3R,4S,5S,6R)-4,5-bis-dodecanoyloxy-6-dodecanoyloxymethyl-2-{2-[(S)-2-(1H-imidazol-4-yl)-1-methoxycarbonyl-ethylamino]-cyclohexylsulfanyl}-tetrahydro-pyran-3-yl ester 
• 215313-26-1 Dodecanoic acid (2S,3R,4S,5S,6R)-4,5-bis-dodecanoyloxy-6-dodecanoyloxymethyl-2-{3-[(S)-2-(1H-imidazol-4-yl)-1-methoxycarbonyl-ethylamino]-cyclohexylsulfanyl}-tetrahydro-pyran-3-yl ester 
• 215313-27-2 Dodecanoic acid (2S,3R,4S,5S,6R)-4,5-bis-dodecanoyloxy-6-dodecanoyloxymethyl-2-{5-[(S)-2-(1H-imidazol-4-yl)-1-methoxycarbonyl-ethylamino]-2,2-dimethyl-cyclohexylsulfanyl}-tetrahydro-pyran-3-yl ester 
• 628737-82-6 histidine phenylhydrazide 
• 2488-14-4 N-(tert-butoxycarbonyl)-L-histidine methyl ester 
• 945265-25-8 Boc-Val-Phe-His-OMe 
• 252372-06-8 Boc-His-His-OMe 
• 69614-04-6 S-(+)-7-Methoxycarbonyl-5,6,7,8-tetrahydroimidazo<1,5-c>pyrimidin-5-on 
• 27748-73-8 Boc-Lys(εZ)-His-OMe 
• 1220697-20-0 C₁₅H₁₇N₃O₄ 

Relevant academic research and scientific papers

Synthesis of Imidazole and Histidine-Derived Cross-Linkers as Analogues of GOLD and Desmosine

Amino acid derivatives with a central cationic heterocyclic core (e.g., imidazolium) are biologically relevant cross-linkers of proteins and advanced glycation end (AGE) products. Here, imidazolium-containing cross-linkers were synthesized from imidazole or histidine by N-alkylation employing aspartate- and glutamate-derived mesylates as key step. Biological investigations were carried out to probe the biocompatibility of these compounds.

Inhibitors of cysteine proteases and methods of use thereof

The disclosure provides compounds with warheads and their use in treating medical diseases or disorders, such as viral infections. Pharmaceutical compositions and methods of making various compounds with warheads are provided. The compounds are contemplated to inhibit proteases, such as the 3C, CL- or 3CL-like protease. Exemplary compounds provided include Formula II-I, where R3, RB are provided herein:

N(?)-2-Naphthylmethoxymethyl-Protected Histidines: Scalable, Racemization-Free Building Blocks for Peptide Synthesis

Histidine (His) racemizes with relative ease during peptide synthesis. One strategy to suppress this racemization is to protect the nitrogen atom of the imidazole moiety in His with a suitable protecting group. Among the numerous protecting groups that have already been tested, the p-methoxybenzyloxymethyl (PMBOM) group on the ?-nitrogen atom effectively suppresses the racemization. However, a large-scale synthesis of N(?)-PMBOM-protected derivatives has hitherto been hampered by the requirement of a freshly prepared unstable reagent. Herein we report the synthesis of N(?)-2-naphthylmethoxymethyl (NAPOM)-protected His derivatives, which can be prepared on a gram scale and do not suffer from the aforementioned instability problems. Furthermore, these NAPOM-protected His derivatives suppress the racemization in Boc- A nd Fmoc-based peptide synthesis.

A Novel N-Substituted Valine Derivative with Unique Peroxisome Proliferator-Activated Receptor γbinding Properties and Biological Activities

A proprietary library of novel N-Aryl-substituted amino acid derivatives bearing a hydroxamate head group allowed the identification of compound 3a that possesses weak proadipogenic and peroxisome proliferator-Activated receptor γ(PPARI) activating properties. The systematic optimization of 3a, in order to improve its PPARγagonist activity, led to the synthesis of compound 7j (N-Aryl-substituted valine derivative) that possesses dual PPARI/PPARα agonistic activity. Structural and kinetic analyses reveal that 7j occupies the typical ligand binding domain of the PPARγagonists with, however, a unique high-Affinity binding mode. Furthermore, 7j is highly effective in preventing cyclin-dependent kinase 5-mediated phosphorylation of PPARγserine 273. Although less proadipogenic than rosiglitazone, 7j significantly increases adipocyte insulin-stimulated glucose uptake and efficiently promotes white-To-brown adipocyte conversion. In addition, 7j prevents oleic acid-induced lipid accumulation in hepatoma cells. The unique biochemical properties and biological activities of compound 7j suggest that it would be a promising candidate for the development of compounds to reduce insulin resistance, obesity, and nonalcoholic fatty liver disease.

Development of an LC–tandem mass spectrometry method for the quantitative analysis of hercynine in human whole blood

Given that the peculiar redox behavior of ergothioneine involves a rapid regeneration process, the measurement of its precursor and redox metabolite hercynine could be particularly useful in assessing its role in oxidative stress or other biological processes. Thus, a LC-MS/MS method for the determination of hercynine concentrations in whole blood was developed. After lysis of red blood cells by cold water, samples were filtered on micro concentrators at a controlled temperature of 4 ?C. The clear filtered fluid was then treated with diethylpyrocarbonate to derivatize hercynine for the analysis by LC-MS/MS. The derivatized analyte was isocratically separated as a carbethoxy derivative on a C18 column with a mobile phase of an aqueous 0.1% v/v formic acid and acetonitrile (95:5). Effluents were monitored by MRM transitions at m/z 270.28→95 and 273.21→95 for hercynine and its deuterated counterpart, respectively. No cross-talk between MRM transitions was observed and a good linearity was found within a range of 35–1120 nmol/L. The LOD and LOQ were, respectively, 10.30 and 31.21 nmol/L with an intraday and intermediate precision below 7%. The average hercynine concentration in whole blood from 30 healthy male volunteers (aged 77 ± 12 years) was 178.5 ± 118.1 nmol/L. Overall, the method is easy to perform, allowing a rapid and accurate assessment of whole blood concentrations of hercynine.

A novel high-capacity immunoadsorbent with PAMAM dendritic spacer arms by click chemistry

Polyamidoamine (PAMAM) dendrimers, bearing multiple peripheral end groups that can be used as clickable modules, make it possible to bind a large number of small-molecule ligands via click chemistry to prepare high-capacity immunoadsorbents. Thus, an immunoadsorbent with PAMAM dendritic spacer arms possessing pseudo-biospecific affinity for IgG from human plasma, Sep-PAMAM-AA, was designed and prepared by click chemistry using sepharose gel as a support and the amino acids His, Phe and Trp as ligands; two sepharose-based control samples, Sep-triazole-His and Sep-PA, with linear spacer arms were prepared using l-histidine and protein A as ligands, respectively. The ligand density and IgG adsorption performance of Sep-PAMAM-AA from human plasma were measured and evaluated. The influences of the structure and generation number of the PAMAM spacer arms on the performances of the products were also investigated. The results indicate that the immunoadsorbent with PAMAM G3 as a spacer arm and His as a ligand, Sep-G3-His, is the best among the prepared immunoadsorbents. Its ligand density reaches 1.58 mmol g?1 sepharose gel, almost 5-fold higher than that of Sep-triazole-His; its IgG adsorption capacity is 28.43 mg g?1, which is higher than those of Sep-triazole-His and Sep-PA. Moreover, Sep-G3-His exhibits a relatively low level of non-specific adsorption, which indicates that the immunoadsorbents with PAMAM as a spacer arm and His as a ligand are expected to have great application prospects in the field of blood purification.

Reevaluating the Substrate Specificity of the L-Type Amino Acid Transporter (LAT1)

The L-type amino acid transporter 1 (LAT1, SLC7A5) transports essential amino acids across the blood-brain barrier (BBB) and into cancer cells. To utilize LAT1 for drug delivery, potent amino acid promoieties are desired, as prodrugs must compete with millimolar concentrations of endogenous amino acids. To better understand ligand-transporter interactions that could improve potency, we developed structural LAT1 models to guide the design of substituted analogues of phenylalanine and histidine. Furthermore, we evaluated the structure-activity relationship (SAR) for both enantiomers of naturally occurring LAT1 substrates. Analogues were tested in cis-inhibition and trans-stimulation cell assays to determine potency and uptake rate. Surprisingly, LAT1 can transport amino acid-like substrates with wide-ranging polarities including those containing ionizable substituents. Additionally, the rate of LAT1 transport was generally nonstereoselective even though enantiomers likely exhibit different binding modes. Our findings have broad implications to the development of new treatments for brain disorders and cancer.

NUCLEOSIDE AND NUCLEOTIDE ANALOGUES AS CD73 INHIBITORS AND THERAPEUTIC USES THEREOF

Nucleoside and nucleotide compounds and analogues, and pharmaceutically acceptable compositions thereof, as inhibitors of CD73 for the treatment of diseases or disorders associated with CD73 activities, especially cancers, and methods of preparing these compounds are disclosed.

Triterpene-amino acid derivative as well as preparation method and application thereof

The invention relates to application of a triterpene derivative in a formula in preparation of medicines for preventing or treating influenza diseases. The definition of substituent groups is shown ina description. The triterpene derivative has obvious inhibiting function on influenza viruses, and can obviously inhibit the influenza viruses from entering cells. The formula is shown in the description.

An Amphotericin B derivative equally potent to Amphotericin B and with increased safety

Amphotericin B is the most potent antimycotic known to date. However due to its large collateral toxicity, its use, although long standing, had been limited. Many attempts have been made to produce derivatives with reduced collateral damage. The molecular mechanism of polyene has also been closely studied for this purpose and understanding it would contribute to the development of safe derivatives. Our study examined polyene action, including chemical synthesis, electrophysiology, pharmacology, toxicology and molecular dynamics. The results were used to support a novel Amphotericin B derivative with increased selectivity: L-histidine methyl ester of Amphotericin B. We found that this derivative has the same form of action as Amphotericin B, i.e. pore formation in the cell membrane. Its reduced dimerization in solution, when compared to Amphotericin B, is at least partially responsible for its increased selectivity. Here we also present the results of preclinical tests, which show that the derivative is just as potent as Amphotericin B and has increased safety.