Category: 169590-42-5

Aziz, Faisal published the artcilePartners in crime: The Lewis Y antigen and fucosyltransferase IV in Helicobacter pylori-induced gastric cancer, Computed Properties of 169590-42-5, the publication is Pharmacology & Therapeutics (2022), 107994, database is CAplus and MEDLINE.

A review. Helicobacter pylori (H. pylori) is a major causative agent of chronic gastritis, gastric ulcer and gastric carcinoma. H. pylori cytotoxin associated antigen A (CagA) plays a crucial role in the development of gastric cancer. Gastric cancer is associated with glycosylation alterations in glycoproteins and glycolipids on the cell surface. H. pylori cytotoxin associated antigen A (CagA) plays a significant role in the progression of gastric cancer through post-translation modification of fucosylation to develop gastric cancer. The involvement of a variety of sugar antigens in the progression and development of gastric cancer has been investigated, including type II blood group antigens. Lewis Y (LeY) is overexpressed on the tumor cell surface either as a glycoprotein or glycolipid. LeY is a difucosylated oligosaccharide, which is catalyzed by fucosyltransferases such as FUT4 (α1,3). FUT4/LeY overexpression may serve as potential correlative biomarkers for the prognosis of gastric cancer. We discuss the various aspects of H. pylori in relation to fucosyltransferases (FUT1-FUT9) and its fucosylated Lewis antigens (LeY, LeX, LeA, and LeB) and gastric cancer. In this review, we summarize the carcinogenic effect of H. pylori CagA in association with LeY and its synthesis enzyme FUT4 in the development of gastric cancer as well as discuss its importance in the prognosis and its inhibition by combination therapy of anti-LeY antibody and celecoxib through MAPK signaling pathway preventing gastric carcinogenesis.

Pharmacology & Therapeutics 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, Computed Properties of 169590-42-5.

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

Lee, Wongyu published the artcilePhotoinduced α-C-H Amination of Cyclic Amine Scaffolds Enabled by Polar-Radical Relay, SDS of cas: 169590-42-5, the publication is Angewandte Chemie, International Edition (2022), 61(25), e202202971, database is CAplus and MEDLINE.

Herein, a polar-radical relay strategy for α-C-H amination of cyclic amines with N-chloro-N-sodio-carbamates is reported. The relay is initiated by in situ generation of a cyclic iminium intermediate using N-iodosuccinimide oxidant as an initiator, which then operates through a series of polar (addition and elimination) and radical (homolysis, hydrogen- and halogen atom transfer) reactions to enable the challenging C-N bond formation in a controlled manner. A broad range of α-amino cyclic amines were readily accessed with excellent regioselectivity, and the superb applicability was further demonstrated by functionalization of biol. relevant compounds

Angewandte Chemie, International Edition 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, SDS of cas: 169590-42-5.

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

Kwon, Kee Woong published the artcileHost-directed anti-mycobacterial activity of colchicine, an anti-gout drug, via strengthened host innate resistance reinforced by the IL-1β/PGE₂ axis, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is British Journal of Pharmacology (2022), 179(15), 3951-3969, database is CAplus and MEDLINE.

To diversify and expand possible tuberculosis (TB) drug candidates and maximize limited global resources, we investigated the effect of colchicine, an FDA-approved anti-gout drug, against Mycobacterium tuberculosis (Mtb) infection because of its immune-modulating effects. We evaluated the intracellular anti-Mtb activity of different concentrations of colchicine in murine bone marrow-derived macrophages (BMDMs). To elucidate the underlying mechanism, RNA sequencing, biol. and chem. inhibition assays, and Western blot, quant. real-time PCR, ELISA (ELISA), and immunohistochem. analyses were employed. Finally, type I interferon-dependent highly TB-susceptible A/J mice were challenged with virulent Mtb H37Rv, and the host-directed therapeutic effect of oral colchicine administration on bacterial burdens and lung inflammation was assessed 30 days post-infection (2.5 mg·kg-1 every 2 days). Colchicine reinforced the anti-Mtb activity of BMDMs without affecting cell viability, indicating that colchicine facilitated macrophage immune activation upon Mtb infection. The results from RNA sequencing, NLRP3 knockout BMDM, IL-1 receptor blockade, and immunohistochem. analyses revealed that this unexpected intracellular anti-Mtb activity of colchicine was mediated through NLRP3-dependent IL-1β signalling and Cox-2-regulated PGE2 production in macrophages. Consequently, the TB-susceptible A/J mouse model showed remarkable protection, with decreased bacterial loads in both the lungs and spleens of oral colchicine-treated mice, with significantly elevated Cox-2 expression at infection sites. The repurposing of colchicine against Mtb infection in this study highlights its unique function in macrophages upon Mtb infection and its novel potential use in treating TB as host-directed or adjunctive therapy.

British Journal of Pharmacology 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, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

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

Kramarczyk, Daniel published the artcileInhibition of celecoxib crystallization by mesoporous silica – Molecular dynamics studies leading to the discovery of the stabilization origin, Synthetic Route of 169590-42-5, the publication is European Journal of Pharmaceutical Sciences (2022), 106132, database is CAplus and MEDLINE.

In this article, the effect of mesoporous silica (MS) on the phys. stability and mol. dynamics of the amorphous form of Celecoxib (CEL) is investigated. It has been proven that the recrystallization process of CEL slows down with increasing the MS content. Beside the elongation of stabilization time with the increase silica content leads to an increase in the amorphous drug fraction remaining after the finished crystallization The conducted analyses show that the observed inhibition of CEL’s recrystallization is associated with the formation of a monomol. drug layer on the silica’s surface. The performed non-isothermal dielec. studies of CEL + MS systems having both fully and partially amorphous CEL shows that the biggest impact of the drug’s the temperature dependences of structural relaxation time τα(T) has a crystalline fraction of the API. Silica, even in high concentration, does not modify the temperature dependence of structural relaxation of CEL.

European Journal of Pharmaceutical Sciences 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, Synthetic Route of 169590-42-5.

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

Poestges, Florian published the artcileBoost of solubility and supersaturation of celecoxib via synergistic interactions of methacrylic acid-ethyl acrylate copolymer (1:1) and hydroxypropyl cellulose in ternary amorphous solid dispersions, SDS of cas: 169590-42-5, the publication is International Journal of Pharmaceutics: X (2022), 100115, database is CAplus and MEDLINE.

A current trend in the development of amorphous solid dispersions (ASDs) is the combination of two polymers for synergistic enhancement in supersaturation of poorly soluble drugs. We investigated the supersaturation potential of celecoxib (CXB) using combinations of methacrylic acid-Et acrylate copolymer (1:1) (EL 100-55) and hydroxypropyl cellulose (HPC) SSL. Initially, the supersaturation potential of single polymers and combinations in various ratios was assessed. While EL 100-55 and HPC SSL alone showed limited potential in solubility enhancement of CXB the combination of both polymers led to a boost of CXB solubility, whereby most promising results were obtained using a 50:50 polymer ratio. Binary and ternary CXB ASDs (10% drug load) were prepared via vacuum compressing molding (VCM) and hot melt extrusion (HME). ASDs were studied by exploring the miscibility and intermol. interactions and tested for their dissolution performance. HPC SSL was identified to be a suitable precipitation inhibitor when added to a fast dissolving CXB: EL 100-55 ASD. Ternary ASDs showed even further dissolution improvement, when processed by HME. The combination of heat and shear stress led to a homogeneous and intimate mixture of EL 100-55 and HPC SSL, resulting in formation of synergistic interactions with pronounced impact on CXB supersaturation

International Journal of Pharmaceutics: X 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, SDS of cas: 169590-42-5.

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

Micovic, Tijana published the artcileIn vitro, in vivo and in silico evaluation of the anti-inflammatory potential of Hyssopus officinalis L. subsp. aristatus (Godr.) Nyman (Lamiaceae), Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Journal of Ethnopharmacology (2022), 115201, database is CAplus and MEDLINE.

Medicinal properties of hyssop have been used in traditional medicine since ancient times, inter alia, in diseases/conditions with an inherent inflammatory process. Aim of the study: Accordingly, the aim of this study was to investigate the anti-inflammatory properties of hyssop herb preparations (essential oil and methanol extracts) in vivo, in vitro and in silico. For in vitro testing of essential oils and extracts of hyssop herb, the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays were used. In vivo anti-inflammatory potential of the extracts (at doses of 50, 100 and 200 mg/kg) was assessed using the carrageenan-induced rat paw edema test. Mol. docking and dynamics were used for in silico testing of the inhibitory activity of chlorogenic (CA) and rosmarinic (RA) acids, as the dominant compounds in the tested methanol extracts against COX-1 and COX-2 enzymes. Significant inhibitory activity was shown in the COX-2 test regarding extracts (essential oils did not exhibit any significant activity). Namely, all analyzed extracts, at a concentration of 20μg/mL, showed a percentage of inhibition of COX-2 enzyme (54.04-63.04%), which did not indicate a statistically significant difference from the pos. control of celecoxib (61.60%) at a concentration of 8.8μM. In vivo testing showed that all methanol extracts of hyssop herb, at the highest test dose of 200 mg/kg in the third and fourth hours, after carrageenan administration, exhibited a statistically significant (p < 0.05) inhibitory effect on the increase in rat paw edema in relation to control. This activity is comparable or higher in relation to the reference substance, indomethacin, at a concentration of 8 mg/kg. The preliminary in silico results suggest that investigated compounds (RA and CA) showed better inhibitory activity against COX-1 and COX-2 than standard non-steroidal anti-inflammatory drug (NSAID), ibuprofen, as evident from the free binding energy (δGbind in kJ mol^-1). The binding energies of the docked compounds to COX-1 and -2 were found to be in the range between -47.4 and -49.2 kJ mol^-1. Ibuprofen, as the one NSAID, for the same receptors targets, showed remarkably higher binding energy (ΔG_bind = -31.3 kJ mol^-1 to COX-1, and ΔG_bind = -30.9 kJ mol^-1 to COX-2). The results obtained not only support the traditional use of hyssop herb in inflammatory conditions in folk medicine, but also open the door to and the need for further in vivo testing of extracts in order to examine the mol. mechanism of anti-inflammatory activity in living systems and possibly develop a new anti-inflammatory drug or supplement.

Journal of Ethnopharmacology 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, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

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

Miek, Laura published the artcileStaphylococcus aureus controls eicosanoid and specialized pro-resolving mediator production via lipoteichoic acid, Computed Properties of 169590-42-5, the publication is Immunology (2022), 166(1), 47-67, database is CAplus and MEDLINE.

Staphylococcus aureus causes severe infections associated with inflammation, such as sepsis or osteomyelitis. Inflammatory processes are regulated by distinct lipid mediators (LMs) but how their biosynthetic pathways are orchestrated in S. aureus infections is elusive. We show that S. aureus strikingly not only modulates pro-inflammatory, but also inflammation-resolving LM pathways in murine osteomyelitis and osteoclasts as well as in human monocyte-derived macrophages (MDMs) with different phenotype. Targeted LM metabololipidomics using ultra-performance liquid chromatog.-tandem mass spectrometry revealed massive generation of LM with distinct LM signature profiles in acute and chronic phases of S. aureus-induced murine osteomyelitis in vivo. In human MDM, S. aureus elevated cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1), but impaired the levels of 15-lipoxygenase-1 (15-LOX-1), with resp. changes in LM signature profiles initiated by these enzymes, i.e., elevated PGE2 and impaired specialized pro-resolving mediators, along with reduced M2-like phenotypic macrophage markers. The cell wall component, lipoteichoic acid (LTA), mimicked the impact of S. aureus elevating COX-2/mPGES-1 expression via NF-κB and p38 MAPK signalling in MDM, while the impairment of 15-LOX-1 correlates with reduced expression of Lamtor1. In conclusion, S. aureus dictates LM pathways via LTA resulting in a shift from anti-inflammatory M2-like towards pro-inflammatory M1-like LM signature profiles.

Immunology 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, Computed Properties of 169590-42-5.

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

Schultz, David C. published the artcilePyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2, Computed Properties of 169590-42-5, the publication is Nature (London, United Kingdom) (2022), 604(7904), 134-140, database is CAplus and MEDLINE.

The SARS-CoV-2 virus has infected more than 261 million people and has led to more than 5 million deaths in the past year and a half¹ (https://www.who.org/). Individuals with SARS-CoV-2 infection typically develop mild-to-severe flu-like symptoms, whereas infection of a subset of individuals leads to severe-to-fatal clin. outcomes. Although vaccines have been rapidly developed to combat SARS-CoV-2, there has been a dearth of antiviral therapeutics. There is an urgent need for therapeutics, which has been amplified by the emerging threats of variants that may evade vaccines. Large-scale efforts are underway to identify antiviral drugs. Here we screened approx. 18,000 drugs for antiviral activity using live virus infection in human respiratory cells and validated 122 drugs with antiviral activity and selectivity against SARS-CoV-2. Among these candidates are 16 nucleoside analogs, the largest category of clin. used antivirals. This included the antivirals remdesivir and molnupiravir, which have been approved for use in COVID-19. RNA viruses rely on a high supply of nucleoside triphosphates from the host to efficiently replicate, and we identified a panel of host nucleoside biosynthesis inhibitors as antiviral. Moreover, we found that combining pyrimidine biosynthesis inhibitors with antiviral nucleoside analogs synergistically inhibits SARS-CoV-2 infection in vitro and in vivo against emerging strains of SARS-CoV-2, suggesting a clin. path forward.

Nature (London, United Kingdom) 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 C4H12ClNO, Computed Properties of 169590-42-5.

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

Jiang, Wenhao published the artcilePGE2 activates EP4 in subchondral bone osteoclasts to regulate osteoarthritis, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Bone Research (2022), 10(1), 27, database is CAplus and MEDLINE.

Prostaglandin E2 (PGE2), a major cyclooxygenase-2 (COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis (OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts (EP4LysM) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in the EP4LysM mice, with reduced Netrin-1 secretion and CGRP-pos. sensory innervation of the subchondral bone. The expression of platelet-derived growth factor-BB (PDGF-BB) was also lower in the EP4LysM mice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in the EP4LysM mice. Finally, we showed that the Gαs/PI3K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA.

Bone Research 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, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

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

Wang, Daoxin published the artcileAlternating Current Electrolysis Enabled Formal C-O/O-H Cross-Metathesis of 4-Alkoxy Anilines with Alcohols, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Angewandte Chemie, International Edition (2022), 61(18), e202201543, database is CAplus and MEDLINE.

A new protocol to achieve the formal C-O/O-H cross-metathesis via a.c. electrolysis was reported. Featuring mild reaction conditions, the protocol allowed readily available 4-alkoxy anilines and alcs. to be converted into a wide range of valuable complex 4-alkoxy anilines I [R = n-Bu, (CH₂)₂OH, (CH₂)₄OH, etc.; R¹ = t-BuC(O), Ts, 4-MeOC₆H₄C(O), etc.; R² = H, 2-Me, 3-Cl, etc.] in highly regioselective and chemoselective manner. Moreover, the present strategy could be used in the late-stage modification of pharmaceuticals as well as biol. active compounds, which demonstrated the potential application.

Angewandte Chemie, International Edition 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 C8H5F3O3, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

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