Month: November 2022

Chen, Jia-Shiong published the artcileCC-01 (chidamide plus celecoxib) modifies the tumor immune microenvironment and reduces tumor progression combined with immune checkpoint inhibitor, Application of 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Scientific Reports (2022), 12(1), 1100, database is CAplus and MEDLINE.

Immune checkpoint inhibitors (ICIs) have shown clin. benefit in solid tumors, with modest rates of clin. response. Hence, improved therapeutic approaches need to be investigated. Herein, we assessed a combination of chidamide plus celecoxib (called CC-01) combined with programmed cell death protein 1 (PD-1) blockade in a CT26 model as potent tumor microenvironment (TME) regulator. The antitumor activity was assessed by measuring tumor size, overall response rate, and survival rate. Immune profiling of tumor-infiltrating lymphocytes was performed by flow cytometry. Tumor tissues were assessed by chip assay to predict the possible pathway. Tumor size was significantly reduced in mice treated with CC-01 combined with or without anti-PD-1 antibody, however the triple combination therapy consistently demonstrated that it significantly increased both the ORR and survival rate in term of clin. applications. In the combination group, immune landscape profiling revealed decreased populations of immunosuppressive regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Anal. of the mouse tumor chip data using Gene Ontol. enrichment anal. of biol. processes revealed that the triple combination upregulated genes associated with responses to interferon-gamma. Our results demonstrated that CC-01 possessed potent TME regulatory properties, augmenting the antitumor effect when combined with ICIs. This antitumor effect was achieved by altering the immune landscape in TILs (tumor-infiltrating lymphocytes) and was associated with immune cell activation in the TME. Furthermore, CC-01 demonstrated potent anticancer immune response activity, mainly reducing the number and function of several immunosuppressive cells. The combination of CC-01 with an ICI will further enhance the anticancer effect and boost the immune response rate. Collectively, our results support the clin. evaluation of CC-01 in combination with ICIs in several advanced cancers.

Scientific Reports published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Application of 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Hussain, Muhammad Asif published the artcileAn efficient hydration of nitriles with ruthenium-supported heterogeneous catalyst in water under moderate conditions, HPLC of Formula: 1453-82-3, the publication is Journal of Industrial and Engineering Chemistry (Amsterdam, Netherlands) (2021), 187-195, database is CAplus.

A facile eco-friendly heterogeneous catalytic system has been developed for amide synthesis that further utilized in pharmaceutical and organic chem. The Ru/MnO₂ catalyst has shown outstanding and unprecedented activity for a wide range of aliphatic and benzylic nitriles in green solvent water at 60°C. The system has also exhibited a remarkable tolerance for selective hydration of heteroatom (e.g. nitrogen, oxygen and sulfur atoms) containing nitriles. Pharmaceutically important nicotinamides and pyrazinamide has been synthesized by hydration of the heteroat. nitriles with appreciable yields and selectivities. Moreover, the Ru/MnO₂ catalyst has employed water as a benign solvent, with more than 30,000 TONs and reusability five times after isolation from the reaction mixture by centrifugation and easy workup that established a path for green environmental and technol. acceptable protocol.

Journal of Industrial and Engineering Chemistry (Amsterdam, Netherlands) published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C6H6N2O, HPLC of Formula: 1453-82-3.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Drsata, J. published the artcileBiological side-effects of potential antituberculotic agents. XIII. Use of serum aspartate aminotransferase for the examination of organ toxicity of thiobenzamides, Formula: C8H9NOS, the publication is Cesko-Slovenska Farmacie (1988), 37(6), 243-5, database is CAplus and MEDLINE.

Ten title compounds (I; R¹ = H, 4-Br, 3-Cl, 4-Cl, 3-Me, 4-Me, 3-MeO, 4-MeO, 4-NMe₂; R² = H, 4-Cl) were screened for hepatotoxicity as indicated by blood serum levels of aspartate aminotransferase (AST). An equation is derived relating the values of Hammett’s constants for I and log AST. The hepatotoxicity of I decreases with an increase in the value of Hammett’s constant

Cesko-Slovenska Farmacie published new progress about 64559-06-4. 64559-06-4 belongs to amides-buliding-blocks, auxiliary class Amine,Benzene,Amide,Ether, name is 3-Methoxybenzothioamide, and the molecular formula is C8H9NOS, Formula: C8H9NOS.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Willis, Julian C. W. published the artcileMutually orthogonal pyrrolysyl-tRNA synthetase/tRNA pairs, Formula: C11H22N2O4, the publication is Nature Chemistry (2018), 10(8), 831-837, database is CAplus and MEDLINE.

Genetically encoding distinct non-canonical amino acids (ncAAs) into proteins synthesized in cells requires mutually orthogonal aminoacyl-tRNA synthetase (aaRS)/tRNA pairs. The pyrrolysyl-tRNA synthetase/^PyltRNA pair from Methanosarcina mazei (Mm) has been engineered to incorporate diverse ncAAs and is commonly considered an ideal pair for genetic code expansion. However, finding new aaRS/tRNA pairs that share the advantages of the MmPylRS/Mm^PyltRNA pair and are orthogonal to both endogenous aaRS/tRNA pairs and the MmPylRS/Mm^PyltRNA pair has proved challenging. Here we demonstrate that several ΔNPylRS/^PyltRNA_CUA pairs, in which PylRS lacks an N-terminal domain, are active, orthogonal and efficiently incorporate ncAAs in Escherichia coli. We create new PylRS/^PyltRNA pairs that are mutually orthogonal to the MmPylRS/Mm^PyltRNA pair and show that transplanting mutations that reprogram the ncAA specificity of MmPylRS into the new PylRS reprograms its substrate specificity. Finally, we show that distinct PylRS/^PyltRNA-derived pairs can function in the same cell, decode distinct codons and incorporate distinct ncAAs.

Nature Chemistry published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C18H15N3O3, Formula: C11H22N2O4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Shcherbakov, Nikolay V. published the artcileRedox-Neutral and Atom-Economic Route to β-Carbolines via Gold-Catalyzed [4 + 2] Cycloaddition of Indolylynamides and Cyanamides, Safety of N,N-Dibenzylcyanamide, the publication is Journal of Organic Chemistry (2021), 86(24), 17804-17815, database is CAplus and MEDLINE.

Gold(I)-catalyzed [4 + 2] cycloaddition of indolylynamides I (R = Ts, Boc; R¹ = R² = H BnO; R³ = tosyl, mesyl, brosyl, etc.; R⁴ = Me, cyclopropyl, benzyl, etc.; R³R⁴ = -C(O)O(CH₂)₂-) and cyanamides (aminonitriles) R⁵CN [R⁵ = diethylamino, methylphenylamino, pyrrolidino, etc.] is an efficient redox-neutral and atom-economic route to diversely substituted 1,3-diamino-α-carbolines II. The protocol operates under mild conditions (Ph₃PAuNTf₂ 5 mol%, DCE, 60°C) with a good tolerance to functional groups (23 examples and yields up to 98%). The obtained α-carboline systems represent a versatile synthetic platform with modifiable substituents for successive functionalizations. Control experiments indicate the crucial role of both the nature of reactants and the identity of employed catalysts in the developed cycloaddition

Journal of Organic Chemistry published new progress about 2451-91-4. 2451-91-4 belongs to amides-buliding-blocks, auxiliary class Nitrile,Amine,Benzene, name is N,N-Dibenzylcyanamide, and the molecular formula is C14H18BNO2, Safety of N,N-Dibenzylcyanamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Hintermann, Samuel published the artcileIdentification of a series of highly potent activators of the Nurr1 signaling pathway, Application In Synthesis of 100377-32-0, the publication is Bioorganic & Medicinal Chemistry Letters (2007), 17(1), 193-196, database is CAplus and MEDLINE.

The nuclear receptor Nurr1 (NR4A2) is critically involved in the development and maintenance of midbrain dopaminergic neurons and is believed to function independently of endogenous activation. The hit identification and SAR studies leading to isoxazolo-pyridinone 7e (I), a highly potent, brain penetrable activator of the Nurr1 signaling pathway, are described.

Bioorganic & Medicinal Chemistry Letters published new progress about 100377-32-0. 100377-32-0 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is N-Methoxy-N-methylisonicotinamide, and the molecular formula is C8H10N2O2, Application In Synthesis of 100377-32-0.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Nechaev, Ilya V. published the artcileThree-Component Reaction of 3,3-Difluorocyclopropenes, s-Tetrazines, and (benzo) Pyridines, Related Products of amides-buliding-blocks, the publication is Journal of Organic Chemistry (2021), 86(1), 1037-1052, database is CAplus and MEDLINE.

A new three-component reaction leading to 1-α-(pyridyl-2-[1,2,4]triazolyl)-2-alkyl-ethanones has been discovered while studying the reactivity of monosubstituted 3,3-difluorocyclopropenes in an inverse electronic demand Diels-Alder (IEDDA) cycloaddition-cycloreversion sequence with s-tetrazines. The reaction involving the above-mentioned reactants and (benzo)pyridine as a third component results in a complex transformation proceeding in mild conditions in a stoichiometric ratio of reactants and has high functional group tolerance (phenols, amides, ethers, carboxylic acids, ketones, and acrylic esters). As a result, simple pyridines are selectively functionalized at the α-position in good isolated yields. The reaction mechanism includes a rare azaphilic [4 + 2]-cycloaddition step between s-tetrazine and intermediate 1-hydroxyindolizine, suggested after byproduct identification and tracked with a deuterium label. To date, it is only the third known example of skewed azaphilic cycloaddition of tetrazine. The reaction is truly three-component and cannot be effectively performed stepwise.

Journal of Organic Chemistry published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C6H6N2O, Related Products of amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Coppi, Elisabetta published the artcileAdenosine A_2B receptors inhibit K⁺ currents and cell differentiation in cultured oligodendrocyte precursor cells and modulate sphingosine-1-phosphate signaling pathway, Related Products of amides-buliding-blocks, the publication is Biochemical Pharmacology (Amsterdam, Netherlands) (2020), 113956, database is CAplus and MEDLINE.

Oligodendrocytes are the only myelinating cells in the brain and differentiate from their progenitors (OPCs) throughout adult life. However, this process fails in demyelinating pathologies. Adenosine is emerging as an important player in OPC differentiation and we recently demonstrated that adenosine A_2A receptors inhibit cell maturation by reducing voltage-dependent K⁺ currents. No data are available to date about the A_2B receptor (A_2BR) subtype. The bioactive lipid mediator sphingosine-1-phosphate (S1P) and its receptors (S1P_1-5) are also crucial modulators of OPC development. An interaction between this pathway and the A_2BR is reported in peripheral cells. We studied the role of A_2BRs in modulating K⁺ currents and cell differentiation in OPC cultures and we investigated a possible interplay with S1P signaling. Our data indicate that the A_2BR agonist BAY60-6583 and its new analog P453 inhibit K⁺ currents in cultured OPC and the effect was prevented by the A_2BR antagonist MRS1706, by K⁺ channel blockers and was differently modulated by the S1P analog FTY720-P. An acute (10 min) exposure of OPCs to BAY60-6583 also increased the phosphorylated form of sphingosine kinase 1 (SphK1). A chronic (7 days) treatment with the same agonist decreased OPC differentiation whereas SphK1/2 inhibition exerted the opposite effect. Furthermore, A_2BR was overexpressed during OPC differentiation, an effect prevented by the pan SphK1/2 inhibitor VPC69047. Finally, A_2BR silenced cells showed increased cell maturation, decreased SphK1 expression and enhanced S1P lyase levels. We conclude that A_2BRs inhibit K⁺ currents and cell differentiation and pos. modulate S1P synthesis in cultured OPCs.

Biochemical Pharmacology (Amsterdam, Netherlands) published new progress about 264622-53-9. 264622-53-9 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Adenosine Receptor, name is N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, and the molecular formula is C27H29N5O5, Related Products of amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Czaplewski, Lloyd G. published the artcileAntibacterial alkoxybenzamide inhibitors of the essential bacterial cell division protein FtsZ, Synthetic Route of 64559-06-4, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(2), 524-527, database is CAplus and MEDLINE.

3-Methoxybenzamide is a weak inhibitor of the essential bacterial cell division protein FtsZ. Exploration of the structure-activity relationships of 3-methoxybenzamide analogs led to the identification of potent anti-staphylococcal compounds

Bioorganic & Medicinal Chemistry Letters published new progress about 64559-06-4. 64559-06-4 belongs to amides-buliding-blocks, auxiliary class Amine,Benzene,Amide,Ether, name is 3-Methoxybenzothioamide, and the molecular formula is C8H9NOS, Synthetic Route of 64559-06-4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Rocca, P. published the artcileFirst metalation of aryl iodides: directed ortho-lithiation of iodopyridines, halogen-dance, and application to synthesis, Computed Properties of 146140-95-6, the publication is Journal of Organic Chemistry (1993), 58(27), 7832-8, database is CAplus.

Metalation of iodopyridines was successfully achieved by LDA at low temperature In many cases, lithiation is ortho directed by the iodo group which subsequently ortho-migrates very fast to give stabilized iodolithiopyridines. This procedure was applied to 2-fluoro- and 2-chloro-3-iodopyridines, 3-fluoro-4-iodopyridine, and 2-chloro-3-fluoro-4-iodopyridine. The resulting lithio intermediates were obtained in high yields before being reacted with electrophiles leading to various polysubstituted pyridines. Some of these iodopyridines were used as key mols. for the preparation of fused polyaromatic alkaloids. Thus, perlolidine (I), δ-carbolines, and 2,10-diazaphenanthrenes were readily prepared in few steps taking advantage of the iodo reactivity for heteroring cross-coupling. Coupling of [2-(pivaloylamino)phenyl]boronic acid with 2-fluoro-4-iodo-3-pyridinecarboxaldehyde gave I.

Journal of Organic Chemistry published new progress about 146140-95-6. 146140-95-6 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (2-Pivalamidophenyl)boronic acid, and the molecular formula is C11H16BNO3, Computed Properties of 146140-95-6.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics