Category: 87694-53-9

Structure Kinetics Relationships and Molecular Dynamics Show Crucial Role for Heterocycle Leaving Group in Irreversible Diacylglycerol Lipase Inhibitors was written by Janssen, Antonius P. A.;van Hengst, Jacob M. A.;Bequignon, Olivier J. M.;Deng, Hui;van Westen, Gerard J. P.;van der Stelt, Mario. And the article was included in Journal of Medicinal Chemistry in 2019.Application of 87694-53-9 This article mentions the following:

Drug discovery programs of covalent irreversible, mechanism-based enzyme inhibitors often focus on optimization of potency as determined by IC₅₀-values in biochem. assays. These assays do not allow the characterization of the binding activity (K_i) and reactivity (k_inact) as individual kinetic parameters of the covalent inhibitors. Here, we report the development of a kinetic substrate assay to study the influence of the acidity (pK_a) of heterocyclic leaving group of triazole urea derivatives as diacylglycerol lipase (DAGL)-浼?inhibitors. Surprisingly, we found that the reactivity of the inhibitors did not correlate with the pK_a of the leaving group, whereas the position of the nitrogen atoms in the heterocyclic core determined to a large extent the binding activity of the inhibitor. This finding was confirmed and clarified by mol. dynamics simulations on the covalently bound Michaelis-Menten complex. A deeper understanding of the binding properties of covalent serine hydrolase inhibitors is expected to aid in the discovery and development of more selective covalent inhibitors. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Application of 87694-53-9).

(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Application of 87694-53-9

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

PADAM reactions of 浼?aminoaldehydes: Identity of major and minor diastereomers from the Passerini reaction was written by Zimuwandeyi, Memory;Kola, Fatima;Lemmerer, Andreas;Brady, Dean;Rousseau, Amanda L.;Bode, Moira L.. And the article was included in Tetrahedron in 2018.Computed Properties of C16H24N2O4 This article mentions the following:

The Passerini reaction was conducted using N-Boc-L-phenylalaninal and a variety of achiral or chiral acids and isocyanides to prepare a library of 27 Passerini products. Reaction diastereoselectivity varied between 1.7:1 and 2.5:1 and in most cases isolation of the individual diastereomers was possible. Passerini products were subjected to a deprotection and acyl migration sequence to give a library of peptidomimetic 浼?hydroxy-灏?acylaminoamides in generally excellent yield. Single crystal X-ray anal. of two of the final products enabled identification of the major diastereomer as having an (R) configuration at the newly-formed stereogenic center, which corresponds to anti-Felkin-Anh addition of the isocyanide to the aldehyde. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Computed Properties of C16H24N2O4).

(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Esters perform as high-grade solvents for a broad array of plastics, plasticizers, resins, and lacquers, and are one of the largest classes of synthetic lubricants on the commercial market. Liquid esters of low volatility serve as softening agents for resins and plastics. Esters also include many industrially important polymers. Polymethyl methacrylate is a glass substitute sold under the names Lucite and Plexiglas; polyethylene terephthalate is used as a film (Mylar) and as textile fibres sold as Terylene, Fortrel, and Dacron.Computed Properties of C16H24N2O4

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

PADAM reactions of 伪-aminoaldehydes: Identity of major and minor diastereomers from the Passerini reaction was written by Zimuwandeyi, Memory;Kola, Fatima;Lemmerer, Andreas;Brady, Dean;Rousseau, Amanda L.;Bode, Moira L.. And the article was included in Tetrahedron in 2018.Computed Properties of C16H24N2O4 This article mentions the following:

The Passerini reaction was conducted using N-Boc-L-phenylalaninal and a variety of achiral or chiral acids and isocyanides to prepare a library of 27 Passerini products. Reaction diastereoselectivity varied between 1.7:1 and 2.5:1 and in most cases isolation of the individual diastereomers was possible. Passerini products were subjected to a deprotection and acyl migration sequence to give a library of peptidomimetic 伪-hydroxy-尾-acylaminoamides in generally excellent yield. Single crystal X-ray anal. of two of the final products enabled identification of the major diastereomer as having an (R) configuration at the newly-formed stereogenic center, which corresponds to anti-Felkin-Anh addition of the isocyanide to the aldehyde. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Computed Properties of C16H24N2O4).

(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Esters perform as high-grade solvents for a broad array of plastics, plasticizers, resins, and lacquers, and are one of the largest classes of synthetic lubricants on the commercial market. Liquid esters of low volatility serve as softening agents for resins and plastics. Esters also include many industrially important polymers. Polymethyl methacrylate is a glass substitute sold under the names Lucite and Plexiglas; polyethylene terephthalate is used as a film (Mylar) and as textile fibres sold as Terylene, Fortrel, and Dacron.Computed Properties of C16H24N2O4

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Substrate Specificity Profiling and Identification of a New Class of Inhibitor for the Major Protease of the SARS Coronavirus was written by Goetz, D. H.;Choe, Y.;Hansell, E.;Chen, Y. T.;McDowell, M.;Jonsson, C. B.;Roush, B. C.;McKerrow, J.;Craik, C. S.. And the article was included in Biochemistry in 2007.Synthetic Route of C16H24N2O4 This article mentions the following:

Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a high rate of mortality. The SARS-associated coronavirus (SARS-CoV) has been identified as the etiol. agent of the disease. Although public health procedures have been effective in combating the spread of SARS, concern remains about the possibility of a recurrence. Various approaches are being pursued for the development of efficacious therapeutics. One promising approach is to develop small mol. inhibitors of the essential major polyprotein processing protease 3Clpro. Here we report a complete description of the tetrapeptide substrate specificity of 3Clpro using fully degenerate peptide libraries consisting of all 160 000 possible naturally occurring tetrapeptides. The substrate specificity data show the expected P1-Gln P2-Leu specificity and elucidate a novel preference for P1-His containing substrates equal to the expected preference for P1-Gln. These data were then used to develop optimal substrates for a high-throughput screen of a 2000 compound small-mol. inhibitor library consisting of known cysteine protease inhibitor scaffolds. We also report the 1.8 Å X-ray crystal structure of 3Clpro bound to an irreversible inhibitor. This inhibitor, an α,β-epoxyketone, inhibits 3Clpro with a k₃/K_i of 0.002 μM^-1 s^-1 in a mode consistent with the substrate specificity data. Finally, we report the successful rational improvement of this scaffold with second generation inhibitors. These data provide the foundation for a rational small-mol. inhibitor design effort based upon the inhibitor scaffold identified, the crystal structure of the complex, and a more complete understanding of P1-P4 substrate specificity. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Synthetic Route of C16H24N2O4).

(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Because of their lack of hydrogen-bond-donating ability, esters do not self-associate. Consequently, esters are more volatile than carboxylic acids of similar molecular weight.Synthetic Route of C16H24N2O4

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding was written by Deng, Hui;Kooijman, Sander;van den Nieuwendijk, Adrianus M. C. H.;Ogasawara, Daisuke;van der Wel, Tom;van Dalen, Floris;Baggelaar, Marc P.;Janssen, Freek J.;van den Berg, Richard J. B. H. N.;den Dulk, Hans;Cravatt, Benjamin F.;Overkleeft, Herman S.;Rensen, Patrick C. N.;van der Stelt, Mario. And the article was included in Journal of Medicinal Chemistry in 2017.Product Details of 87694-53-9 This article mentions the following:

Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoyl glycerol (2-AG) that activates cannabinoid CB₁ receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4-substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5-position of the piperidine ring provided ultrapotent inhibitor I (DH376) with picomolar activity. Compound I temporarily reduces fasting-induced refeeding of mice, thereby emulating the effect of cannabinoid CB₁-receptor inverse agonists. This was mirrored by II (DO34) but also by the neg. control compound III (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple mol. targets. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Product Details of 87694-53-9).

(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Product Details of 87694-53-9

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

α-Amino ketones from amino acids as precursors for the Knorr pyrrole synthesis was written by Hamby, James M.;Hodges, John C.. And the article was included in Heterocycles in 1993.Product Details of 87694-53-9 This article mentions the following:

A useful and versatile modification of the Knorr pyrrole synthesis is described. Key α-amino ketone intermediates for the Knorr condensation were readily prepared from the N-methoxy-N-methylamides of amino acids and condensed with 1,3-dicarbonyl compounds to afford tetrasubstituted pyrroles, e.g. I, in good yields. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Product Details of 87694-53-9).

(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Esters perform as high-grade solvents for a broad array of plastics, plasticizers, resins, and lacquers, and are one of the largest classes of synthetic lubricants on the commercial market. Polyesters are important plastics, with monomers linked by ester moieties. Liquid esters of low volatility serve as softening agents for resins and plastics. Esters also include many industrially important polymers. Polymethyl methacrylate is a glass substitute sold under the names Lucite and Plexiglas; polyethylene terephthalate is used as a film (Mylar) and as textile fibres sold as Terylene, Fortrel, and Dacron.Product Details of 87694-53-9

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthesis of Nα-protected amino acid/peptide Weinreb amides employing N,N’-carbonyldiimidazole as activating agent; studies on docking and antibacterial activities was written by Uma, K.;Lalithamba, H. S.;Raghavendra, M.;Chandramohan, Vivek;Anupama, C.. And the article was included in ARKIVOC (Gainesville, FL, United States) in 2016.Computed Properties of C16H24N2O4 This article mentions the following:

An efficient method for the synthesis of Nα-protected amino/peptide Weinreb amides (N-methoxy-N-methylamides) employing N,N’-carbonyldiimidazole (CDI) has been achieved. Nα-protected amino/peptide acids were treated with N,N’-carbonyldiimidazole, followed by the addition of N,O-dimethylhydroxylamine hydrochloride salt to yield the desired compounds The synthesized compounds were mainly gums, a few were solids, after the simple workup, and were characterized by IR, ¹H NMR, ¹³C NMR and HRMS. The Weinreb amides were subjected to in silico studies, to predict the preferred orientation and binding affinity between the mols. using scoring functions. The ligand N-Fmoc-L-Phe-N(OCH₃)CH₃ showed min. binding energy – 29.85 kcal/mol with Escherichia coli and the ligand N-Fmoc-L-Ala-N(OCH₃)CH₃ showed min. binding energy -24.79 kcal/mol with Pseudomonas aeruginosa, -25.01 kcal/mol with Staphylococcus aureus. Based on the min. binding energies, antibacterial activities have been conducted for a few of the synthesized compounds In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Computed Properties of C16H24N2O4).

(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Computed Properties of C16H24N2O4

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Improved Total Synthesis of Tubulysins and Design, Synthesis, and Biological Evaluation of New Tubulysins with Highly Potent Cytotoxicities against Cancer Cells as Potential Payloads for Antibody-Drug Conjugates was written by Nicolaou, K. C.;Erande, Rohan D.;Yin, Jun;Vourloumis, Dionisios;Aujay, Monette;Sandoval, Joseph;Munneke, Stefan;Gavrilyuk, Julia. And the article was included in Journal of the American Chemical Society in 2018.Formula: C16H24N2O4 This article mentions the following:

Improved, streamlined total syntheses of natural tubulysins such as V and U, I (R = β-OH, β-OAc, resp.), and pretubulysin D I (R = H), and their application to the synthesis of designed tubulysin analogs, are described. Cytotoxicity evaluation of the synthesized compounds against certain cancer cell lines revealed a number of novel analogs with exceptional potencies [e.g., II: IC₅₀ = 40 pM against MES SA (uterine sarcoma) cell line; IC₅₀ = 6 pM against HEK 293T (human embryonic kidney cancer) cell line; and IC₅₀ = 1.54 nM against MES SA DX (MES SA with marked multidrug resistance) cell line]. These studies led to a set of valuable structure-activity relationships that provide guidance to further mol. design, synthesis, and biol. evaluation studies. The extremely potent cytotoxic compounds discovered in these investigations are highly desirable as potential payloads for antibody-drug conjugates and other drug delivery systems for personalized targeted cancer chemotherapies. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Formula: C16H24N2O4).

(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Formula: C16H24N2O4

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Inhibition of human leukocyte elastase (HLE) by N-substituted peptidyl trifluoromethyl ketones was written by Skiles, Jerry W.;Fuchs, Victor;Miao, Clara;Sorcek, Ronald;Grozinger, Karl G.;Mauldin, Scott C.;Vitous, Jana;Mui, Philip W.;Jacober, Stephen. And the article was included in Journal of Medicinal Chemistry in 1992.Category: esters-buliding-blocks This article mentions the following:

A series of tripeptides possessing trifluoromethyl or aryl kinase residues at P₁ were prepared and evaluated both in vitro and in vivo as potential inhibitors of human leukocyte elastase (HLE). Tripeptides containing nonnaturally occurring N-substituted glycine residues at the P₂-position have been demonstrated to be potent in vitro inhibitors of HLE, with IC₅₀ values in the submicromolar range. Sterically demanding substituents on the P₂-nitrogen have no detrimental effect on in vitro potency. The inhibition process presumably acts via hemiketal formation with the active site Ser¹⁹⁵ of HLE, and is facilitated by the strongly electron withdrawing trifluoromethyl functionality. Deletion of the amino acid at the P³-subsite region affords inactive compounds Valine is the preferred residue at the P₁-position, whereas the corresponding glycine, alanine, α,α-dimethylglycine, or phenylalanine analogs are all inactive. The compounds described herein all confer a high degree of in vitro specificity when tested against representing cysteine, aspartyl, metallo, and other serine proteases. One of the most potent in vitro inhibitors is tripeptide trifluoromethyl ketone I (IC₅₀ = 0.084 μM). I was also tested in hamsters in an elastase-induced pulmonary hemorrhage (EPH) model. In this model, intratracheal (it) administration of I, 5 min prior to HLE challenge, effectively inhibited hemorrhage in a dose-dependent manner with an ED₅₀ of 4.8 μg. The administration of 20 μg (i.t.) of I 24, 48 and 72 h prior to HLE challenge exhibits significant inhibition against hemorrhage at all time points (97%, 64% and 49%, resp.). In a 21-day chronic model of emphysema in hamsters, 200 μg of HLE administered i.t. caused an elastase-induced emphysema in the lungs which can be quantitated histol. utilizing image anal. In this assay, I significantly inhibited pulmonary lesions associated with septal destruction and increased alveolar spaces, when dosed at 20 μg i.t. 5 min prior to challenge with HLE. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Category: esters-buliding-blocks).

(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Category: esters-buliding-blocks

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthesis of enaminone-based vinylogous peptides was written by Senica, Luka;Groselj, Uros;Kasunic, Marta;Kocar, Drago;Stanovnik, Branko;Svete, Jurij. And the article was included in European Journal of Organic Chemistry in 2014.Recommanded Product: 87694-53-9 This article mentions the following:

Vinylogous peptides 3 [E-I or Z-I (Boc = tert-butoxycarbonyl; R¹ = H, Me, Bn; AA = amino acid or peptide)] with a vinyl fragment inserted into the peptide C-N bond were prepared from ynones (II) (R¹ = H, Me, Bn) and enaminones (E-III) (R¹ = H, Me, Bn) that are easily available from Boc-protected α-amino acids. Coupling at the C terminus was achieved by 1,4-addition of amino esters to the C C bond in II or by substitution of the NMe₂ group in III to give N-terminal vinylogous peptides. Coupling at the N terminus of I and III in contrast, required temporary protection of the acidolytically labile enamino moiety. Cyclization of II or III with hydroxylamine, removal of the Boc group with HBr-AcOH, acylation of free amine hydrobromides (IV) (R¹ = H, Me, Bn) with BocGlyOH, and hydrogenolytic deprotection of the enamino moiety in the presence of GlyOMe led to tripeptides with vinylogous amide as the central building block. Thus, the present method enables incorporation of vinylogous amide (building blocks) BBs into oligopeptides. However, the preparation of oligomers with consecutive vinylogous BBs represents the next synthetic challenge to be met. These preliminary results clearly indicate the viability of this synthetic approach, which enables the incorporation of vinylogous amides into a peptide chain. Vinylogous peptides might be interesting or even useful for various applications, for example, in medicinal chem., chem. biol., and in materials science. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Recommanded Product: 87694-53-9).

(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Esters contain a carbonyl center, which gives rise to 120° C–C–O and O–C–O angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C–O–C bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. Recommanded Product: 87694-53-9

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics