27610-07-7

Upstream product

• 13139-15-6 N-tert-butoxycarbonyl-L-leucine 
• 5680-79-5 glycine ethyl ester hydrochloride 
• 126748-97-8 C₁₉H₃₆N₃O₇P 
• 616-34-2 methoxycarbonylmethylamine 
• 75243-94-6 (S)-2-tert-Butoxycarbonylamino-4-methyl-pentanoic acid 3-oxo-2-phenyl-3H-inden-1-yl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 13139-15-6 Boc-DL-Leu-OH 
• 67-56-1 methanol 
• 137169-45-0 Boc-Leu-SH 
• 24608-52-4 tert-butyl chloroformate 
• 61-90-5 L-leucine 
• 33900-00-4 (S)-2-tert-Butoxycarbonylamino-4-methyl-pentanoic acid pyridin-2-yl ester 

Downstream Products

• 1391105-08-0 Boc-Cys(Trt)-Pro-Leu-Gly-OMe 
• 1391105-10-4 Boc-Asn(Trt)-Cys(Trt)-Pro-Leu-Gly-OMe 
• 17912-60-6 H-Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH₂ 
• 50-56-6 oxytocin 
• 32991-17-6 2-((2S)-2-((tert-butoxycarbonyl)amino)-4-methylpentanamido)acetic acid 
• 603111-42-8 N^α-(4-trifluoromethoxybenzoyl)-Arg(NO2)-Leu-Gly-OH 

Relevant academic research and scientific papers

Electrochemical Dimethyl Sulfide-Mediated Esterification of Amino Acids

Dimethyl sulfide-mediated electrochemical synthetic strategy for esterification of amino acids has been reported. A series of amino acids could react smoothly with alcohols, affording the desired esterification products with good efficiency. Importantly, the tolerance of peptides and gram-scale synthesis shed light on the utility of this protocol. Mechanistically, the dimethyl sulfide as a mediator plays an essential role in the transformation of amino acids.

Structure-Based Design of Inhibitors Selective for Human Proteasome β2c or β2i Subunits

Subunit-selective proteasome inhibitors are valuable tools to assess the biological and medicinal relevance of individual proteasome active sites. Whereas the inhibitors for the β1c, β1i, β5c, and β5i subunits exploit the differences in the substrate-binding channels identified by X-ray crystallography, compounds selectively targeting β2c or β2i could not yet be rationally designed because of the high structural similarity of these two subunits. Here, we report the development, chemical synthesis, and biological screening of a compound library that led to the identification of the β2c- and β2i-selective compounds LU-002c (4; IC50 β2c: 8 nM, IC50 β2i/β2c: 40-fold) and LU-002i (5; IC50 β2i: 220 nM, IC50 β2c/β2i: 45-fold), respectively. Co-crystal structures with β2 humanized yeast proteasomes visualize protein-ligand interactions crucial for subunit specificity. Altogether, organic syntheses, activity-based protein profiling, yeast mutagenesis, and structural biology allowed us to decipher significant differences of β2 substrate-binding channels and to complete the set of subunit-selective proteasome inhibitors.

COMBINATION OF A SELECTIVE HISTONE DEACETYLASE 3 (HDAC3) INHIBITOR AND AN IMMUNOTHERAPY AGENT FOR THE TREATMENT OF CANCER

Aspects of the disclosure relate to compositions, kits, and methods for the treatment of cancer that utilize a selective histonc deacetylase 3 (HDAC3) inhibitor. In some aspects, the compositions, kits, and methods relate to use of a selective HDAC3 inhibitor in combination with an immunotherapy agent (e.g., an immune checkpoint inhibitor).

Preparation and biological evaluation of soluble tetrapeptide epoxyketone proteasome inhibitors

A series of novel tetrapeptidyl epoxyketone inhibitors of 20S proteasome was designed and synthesized. To fully understand the SAR, various groups at R1, R2, R3, R4 and R5 positions, including aromatic and aliphatic substituents were designed, synthesized and biologically assayed. Based on the enzymatic results, seven compounds were selected to evaluate their cellular activities and soluble compound 36 showed strong potency against human multiple myeloma (MM) cell lines. Microsomal stability results indicated that compound 36 was more stable in mice, rat and human microsomes than marketed carfilzomib. The in vivo activities of this compound were evaluated with the xenograft mice models of MM cell lines ARH77 and RPMI-8226 with luciferase expression and the T/C value of the two models were 49.5% and 37.6%, respectively. To evaluate the potential cardiovascular toxicity, inhibition of hERG ion channel in HEK293 cells by compound 36 and carfilzomib was carried out. The results indicated that 36 had no binding affinity for the hERG ion channel while carfilzomib could bind it with IC50 of 92.1 μM.

Novel l-prolyl-l-leucylglycinamide (PLG) tripeptidomimetics based on a 2-azanorbornane scaffold as positive allosteric modulators of the D2R

An efficient and straightforward orthogonal methodology was successfully developed to achieve constrained l-prolyl-l-leucylglycinamide (PLG) analogues starting from two proline mimetics based on a 2-azanorbornane scaffold. A preliminary dopamine D2 receptor radiolabeled binding assay with [3H]-N-propylnorapomorphine shows that enantiopurity of PLG peptidomimetics based on 2-azanorbornane is a requirement to achieve statistically significant positive modulators of the D2 receptor. This is the first documented active peptidomimetic of PLG whose bioactivity is not correlated with the C-terminal carboxamide pharmacophore and which cannot adopt the hypothesized type II β-turn conformation.

Design and Synthesis of Simplified Largazole Analogues as Isoform-Selective Human Lysine Deacetylase Inhibitors

Selective inhibition of KDAC isoforms while maintaining potency remains a challenge. Using the largazole macrocyclic depsipeptide structure as a starting point for developing new KDACIs with increased selectivity, a combination of four different simplified largazole analogue (SLA) scaffolds with diverse zinc-binding groups (for a total of 60 compounds) were designed, synthesized, and evaluated against class I KDACs 1, 3, and 8, and class II KDAC6. Experimental evidence as well as molecular docking poses converged to establish the cyclic tetrapeptides (CTPs) as the primary determinant of both potency and selectivity by influencing the correct alignment of the zinc-binding group in the KDAC active site, providing a further basis for developing new KDACIs of higher isoform selectivity and potency.

ISOFORM-SELECTIVE LYSINE DEACETYLASE INHIBITORS

Isoform-selective lysine deacetylase inhibitors are described. Inhibitors of the lysine deacetylase enzyme are useful as antitumor drugs and for treating addiction, asthma, cardio-vascular disease, immunosuppression, neurodegenerative diseases, sepsis, sickle-cell disease, uveal melanoma and termination of viral latency, particularly HIV-1 latency.

First Total Synthesis and Biological Potential of a Heptacyclopeptide of Plant Origin

Synthesis of a natural glycine-rich heptacyclopeptide - mahafacyclin A (7) was accomplished by solution-phase technique of peptide synthesis via coupling of tetrapeptide unit Boc-L-Thr-L-Ile-L-Leu-Gly-OH with tripeptide unit L-Val-L-Phe-Gly-OMe followed b

Inhibitors of histone deacetylase

The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R2a, R2b, R2c, R5 and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.

AGRICULTURAL PLANT-PROTECTING AGENTS CONTAINING DIPEPTIDE DERIVATIVE AS ACTIVE INGREDIENT

Provided is an agricultural plant-protecting agent including a dipeptide derivative or an agro-pharmaceutically acceptable salt thereof as an active ingredient, which has a plant disease-preventing effect, a plant growth-promoting effect, and a plant immunity-activating effect.