Category: 169590-42-5

Deal, Brooke published the artcileBehavioral and inflammatory sex differences revealed by celecoxib nanotherapeutic treatment of peripheral neuroinflammation, Name: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Scientific Reports (2022), 12(1), 8472, database is CAplus and MEDLINE.

Abstract: Neuropathic pain affects millions of people worldwide, yet the mol. mechanisms of how it develops and persists are poorly understood. Given that males have historically been utilized as the primary sex in preclin. studies, less is known about the female neuroinflammatory response to injury, formation of pain, or response to pain-relieving therapies. Macrophages contribute to the development of neuroinflammatory pain via the activation of their cyclooxygenase-2 (COX-2) enzyme, which leads to the production of prostaglandin E₂ (PGE₂). PGE₂ activates nociception and influences addnl. leukocyte infiltration. Attenuation of COX-2 activity decreases inflammatory pain, most commonly achieved by nonsteroidal anti-inflammatory drugs (NSAIDs), yet NSAIDs are considered ineffective for neuropathic pain due to off target toxicity. Using chronic constriction injury of the rat sciatic nerve, we show that males and females exhibit quant. the same degree of mech. allodynia post injury. Furthermore, a low-dose nanotherapeutic containing the NSAID celecoxib is phagocytosed by circulating monocytes that then naturally accumulate at sites of injury as macrophages. Using this nanotherapeutic, we show that treated males exhibit complete reversal of hypersensitivity, while the same dose of nanotherapeutic in females provides an attenuated relief. The difference in behavioral response to the nanotherapy is reflected in the reduction of infiltrating macrophages at the site of injury. The observations contained in this study reinforce the notion that female neuroinflammation is different than males.

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, Name: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.

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

Ghitman, Jana published the artcileMacrophage-targeted mannose-decorated PLGA-vegetable oil hybrid nanoparticles loaded with anti-inflammatory agents, SDS of cas: 169590-42-5, the publication is Colloids and Surfaces, B: Biointerfaces (2022), 112423, database is CAplus and MEDLINE.

This work pledge to extend the therapeutic windows of hybrid nanoparticulate systems by engineering mannose-decorated hybrid nanoparticles based on poly lactic-co-glycolic acid (PLGA) and vegetable oil for efficient delivery of two lipophilic anti-inflammatory therapeutics (Celecoxib-CL and Indomethacin-IMC) to macrophages. The mannose surface modification of nanoparticles is achieved via O-palmitoyl-mannose spacer during the emulsification and nanoparticles assembly process. The impact of targeting motif on the hydrodynamic features (RH, PdI), stability (ζ-potential), drug encapsulation efficiency (DEE) is thoroughly investigated. Besides, the in vitro biocompatibility (MTT, LDH) and susceptibility of mannose-decorated formulations to macrophage as well their immunomodulatory activity (ELISA) are also evaluated. The monomodal distributed mannose-decorated nanoparticles are in the range of nanometric size (RH < 115 nm) with PdI < 0.20 and good encapsulation efficiency (DEE = 46.15% for CL and 76.20% for IMC). The quant. investigation of macrophage uptake shows a 2-fold increase in fluorescence (RFU) of cells treated with mannose-decorated formulations as compared to non-decorated ones (p < 0.001) suggesting an enhanced cell uptake resp. improved macrophage targeting while the results of ELISA experiments suggest the potential immunomodulatory properties of the designed mannose-decorated hybrid formulations.

Colloids and Surfaces, B: Biointerfaces 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

Aydogdu, Ozgu published the artcileTreatment with the soluble guanylate cyclase activator BAY 60-2770 normalizes bladder function in an in vivo rat model of chronic prostatitis, HPLC of Formula: 169590-42-5, the publication is European Journal of Pharmacology (2022), 175052, database is CAplus and MEDLINE.

Chronic pelvic pain syndrome (CPPS) is a common and bothersome condition for which no pharmacol. treatment options with acceptable efficacy exist. The aim of this study was to investigate the effects of the soluble guanylate cyclase (sGC) activator BAY 60-2770 and the COX-2 inhibitor celecoxib on bladder function in a rat model of CPPS. Forty-eight male Sprague-Dawley rats were intraprostatically injected with either saline, serving as control, or zymosan, to induce prostatitis. On days 8-20, the rats were treated with either dimethylsulfoxide (DMSO; vehicle), celecoxib, BAY 60-2770 or a combination of celecoxib and BAY 60-2770. Thereafter, micturition parameters were assessed in a metabolic cage and urine samples were collected. The following day, cystometry was performed. Subsequently, the urinary bladder and prostate were removed and examined histopathol. Induction of prostatitis led to a significant increase of micturition frequency and corresponding decrease of volume per micturition. These alterations were ameliorated by celecoxib, and completely normalized by BAY 60-2770. Induction of prostatitis led to a significantly increased number of non-voiding contractions, decreased bladder compliance and increased voiding time. These parameters were normalized by treatment with BAY 60-2770, either alone or in combination with celecoxib. The immunohistochem. anal. showed signs of prostate inflammation, but not bladder inflammation. Induction of prostatitis led to significant impairment in bladder function. These alterations could be prevented by BAY 60-2770, alone or in combination with celecoxib. This is the first study to show that sGC activators could be a promising option for the treatment of CPPS.

European 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, HPLC of Formula: 169590-42-5.

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

Bell, Charlotte R. published the artcileChemotherapy-induced COX-2 upregulation by cancer cells defines their inflammatory properties and limits the efficacy of chemoimmunotherapy combinations, Computed Properties of 169590-42-5, the publication is Nature Communications (2022), 13(1), 2063, database is CAplus and MEDLINE.

Cytotoxic therapies, besides directly inducing cancer cell death, can stimulate immune-dependent tumor growth control or paradoxically accelerate tumor progression. The underlying mechanisms dictating these opposing outcomes are poorly defined. Here, we show that cytotoxic therapy acutely upregulates cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) production in cancer cells with pre-existing COX-2 activity. Screening a compound library of 1280 approved drugs, we find that all classes of chemotherapy drugs enhance COX-2 transcription while arresting cancer cell proliferation. Genetic manipulation of COX-2 expression or its gene promoter region uncover how augmented COX-2/PGE2 activity post-treatment profoundly alters the inflammatory properties of chemotherapy-treated cancer cells in vivo. Pharmacol. COX-2 inhibition boosts the efficacy of the combination of chemotherapy and PD-1 blockade. Crucially, in a poorly immunogenic breast cancer model, only the triple therapy unleashes tumor growth control and significantly reduces relapse and spontaneous metastatic spread in an adjuvant setting. Our findings suggest COX-2/PGE2 upregulation by dying cancer cells acts as a major barrier to cytotoxic therapy-driven tumor immunity and uncover a strategy to improve the outcomes of immunotherapy and chemotherapy combinations.

Nature Communications 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

Hamoud, Mohamed M. S. published the artcileDesign and Synthesis of Novel 1,3,4-Oxadiazole and 1,2,4-Triazole Derivatives as Cyclooxygenase-2 Inhibitors with Anti-inflammatory and Antioxidant activity in LPS-stimulated RAW264.7 Macrophages, SDS of cas: 169590-42-5, the publication is Bioorganic Chemistry (2022), 105808, database is CAplus and MEDLINE.

In an attempt to obtain new candidates with potential anti-inflammatory activity, two series of 1,3,4-oxadiazole based derivatives (8a-g) and 1,2,4-triazole based derivatives (10a,b and 11a-g) were synthesized and evaluated for their COX-1/COX-2 inhibitory activity. In vitro assays showed potent COX-2 inhibitory activity and selectivity of the novel designed compounds (IC₅₀ = 0.04 – 0.16 μM, SI = 60.71 – 337.5) compared to celecoxib (IC₅₀ = 0.045 μM, SI = 326.67). The anti-inflammatory and antioxidant activity of the synthesized compounds was investigated via testing their ability to inhibit pro-inflammatory [tumor necrosis factor (TNF-α) and interleukin-6 (IL-6)] and oxidative stress [nitric oxide (NO) and reactive oxygen species (ROS)] markers production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Most of the novel compounds exhibited potent anti-inflammatory and antioxidant activity. In particular, the novel compounds showed excellent IL-6 inhibitory activity (IC₅₀ = 0.96 – 11.14 μM) when compared to celecoxib (IC₅₀ = 13.04 μM) and diclofenac sodium (IC₅₀ = 22.97 μM). Moreover, the most potent and selective COX-2 inhibitor 11c (IC₅₀ = 0.04 μM, SI = 337.5) displayed significantly higher activity against NO and ROS production compared to celecoxib (IC₅₀ = 2.60 and 3.01 μM vs. 16.47 and 14.30 μM, resp.). Mol. modeling studies of the novel designed mols. into COX-2 active sites analyzed their binding affinity. In-silico simulation studies indicated their acceptable physicochem. properties and pharmacokinetic profiles. This study suggests that the novel synthesized COX-2 inhibitors exert potent anti-inflammatory and antioxidant activity, highlighting their potential as promising therapeutic agents for the treatment of inflammation and oxidative stress-related diseases.

Bioorganic Chemistry 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

Abdelall, Eman K. A. published the artcileTrimethoxyphenyl containing compounds: Synthesis, biological evaluation, nitric oxide release, modeling, histochemical and histopathological studies, SDS of cas: 169590-42-5, the publication is Bioorganic Chemistry (2022), 105806, database is CAplus and MEDLINE.

Novel series of trimethoxy Ph containing chalcone 3, 5, 6, 7, pyrazoline 4a&b, 9a-h and pyrazole 10a&b scaffolds were designed and synthesized. They were characterized by spectral data and elemental analyses. All newly synthesized compounds were screened for their in vitro COX-1/COX-2 inhibitory activities and in vivo anti-inflammatory activity. All the target compounds showed COX-2 inhibitory activity over COX-1. Compound 5c was the most active derivative with higher COX-2 inhibitory activity (IC50 = 0.039μM) than celecoxib (IC50 = 0.045μM), and selectivity index value of 321.28 nearly equal to that of celecoxib (S.I. = 326.66). Four addnl. derivatives 5a, 6, 8b and 9f exhibited excellent COX-2 inhibitory activity (IC₅₀ = 0.041 – 0.049μM) if compared to the reference drug, celecoxib, with selectivity index values (S.I. = 230.61 – 278.05). Addnl., prolonged in vivo A. I activity was observed in compounds 9e, 9 g, 10a and 10b with % inhibition ranged from 33.21 to 44.52%, after 7 h from carrageenan injection. Compound 9e appeared normal without degeneration similar to celecoxib as resulted from histolopathogical study. Compounds containing NO releasing moieties, 7, 10a and 10b were assesses to overcome the gastrointestinal side effects. Mol. modeling study was operated and achieved a parallel correlation with in vitro COX-2 assay results. Pharmacokinetic study for all the prepared compounds was developed.

Bioorganic Chemistry 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

Abdallah el hadj, A. published the artcileAI-PCSAFT approach: New high predictive method for estimating PC-SAFT pure component properties and phase equilibria parameters, Computed Properties of 169590-42-5, the publication is Fluid Phase Equilibria (2022), 113297, database is CAplus.

In this work, a new approach based on the association of Artificial intelligence method (AI) and PC-SAFT equation of state is applied to conceive a model for estimating the solubility of solid drugs in supercritical carbon dioxide. Neuro-equation of state approach (NES) is the new technique that takes benefit from the advantages of both ANN and PC-SAFT equation of state. The new method decomposes into three main stages, first the optimization of direct ANN for predicting solids-scCO₂ phase equilibrium (where 15 binary systems are used), then the ANN inverse is performed to be an alternative to group contribution methods (GCMs) for estimating the pure components and phys. properties (reduce the uncertainty committed in estimating these properties) and enhance the PCSAFT equation of state to estimate phase equilibrium parameters and finally, ANN-PCSAFT approach is used to estimate the solubility of 213 solid solutes in supercritical carbon dioxide. The performance strategy has been carried out using a linear regression anal. of the predicted vs. exptl. outputs, as an indication of the predictive ability of the developed method. The new approach is successfully applied to the phase equilibrium modeling for 213 binary systems with high accuracy (the comparison in terms of average absolute relative deviation (AARD %) showed a variation from 2 to 6%) and allowed to enhance the phase equilibrium modeling by reducing the number of optimized parameters and surpass the main drawbacks faced in this area mainly the non-availability of phys. properties and EOS pure component properties and the limitation of the equation of state.

Fluid Phase Equilibria 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

Santhosh, Akhil published the artcileRandomized double-blind, placebo-controlled study of topical diclofenac in the prevention of hand-foot syndrome in patients receiving capecitabine (the D-TORCH study), SDS of cas: 169590-42-5, the publication is Trials (2022), 23(1), 420, database is CAplus and MEDLINE.

Abstract: Introduction: Hand-foot syndrome (HFS) is a common cutaneous side effect of capecitabine therapy. Apart from oral cyclooxygenase-2 (COX-2) inhibitor (celecoxib), there are no proven strategies for the prevention of HFS. However, celecoxib is associated with significant cardiotoxicity. To date, no study has evaluated the role of topical COX inhibitor, diclofenac. In this study, we aim to compare topical 1% diclofenac gel with placebo in the prevention of capecitabine-induced HFS. Methods: This is a randomized, placebo-controlled, double-blind, parallel-group superiority trial: the Diclofenac Topical in Reducing Capecitabine induced HFS (D-TORCH) study. A total of 264 patients with breast and gastrointestinal malignancies will be randomly allocated (stratified by sex and type of therapy [monotherapy or combination regimen with capecitabine]) to receive either 1% topical diclofenac or placebo that will be applied over the palmar and dorsal surface of the hands twice daily while taking capecitabine for 12 wk. The patients will be followed up until the end of four cycles. The primary objective of this study is to compare the effect of topical diclofenac with placebo in preventing HFS (incidence of NCI CTCAEv5.0 grade 2 or higher HFS). The secondary objective is to compare the effect of topical diclofenac with placebo on preventing all grades of HFS (incidence of NCI CTCv5.0 all grade HFS), time to develop HFS (from the start of capecitabine), patient-reported outcomes (PROs) (HF-HRQoL questionnaire), adherence with the application (self-reported), capecitabine dose changes (number of patients with dose modifications due to HFS) and safety profile (NCICTCv5.0 all grade HFS) Discussion: The D-TORCH study aims to determine if 1% topical diclofenac reduces the incidence of grade 2 or higher HFS in patients receiving capecitabine. To date, there have been a lot of trials for hand-foot syndrome prevention using agents like pyridoxine, vitamin E, carvedilol, and various polyherbal formulations, but none has been found successful. If the trial meets the primary end point, 1% topical diclofenac will be the new standard of care for HFS prevention. Trial registration: Clin. Trials Registry of India CTRI/2021/01/030592. Prospectively registered on Jan. 19, 2021

Trials 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

Lucas, Dominic published the artcileDesigning highly porous amorphous celecoxib particles by spray freeze drying leads to accelerated drug absorption in-vivo, Application In Synthesis of 169590-42-5, the publication is European Journal of Pharmaceutics and Biopharmaceutics (2022), 20-28, database is CAplus and MEDLINE.

Poorly water-soluble drugs are still a major challenge to overcome in order to achieve sufficiently high oral bioavailability. Spray freeze drying (SFD) is proposed here as an alternative for the preparation of amorphous, free-flowing porous celecoxib spheres for enhanced drug dissolution Tert-Bu alc. solutions of celecoxib + excipient (povidone, hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and Soluplus) at variable ratios were sprayed into a cooled spray tower, followed by vacuum freeze drying. Final porous particles were free-flowing, highly spherical (circularity ≥ 0.96) and mean diameters ranging from 210 to 800μm, depending on excipient and drug content. XRPD measurements showed that Celecoxib was amorphous in all formulations and remained stable during 6 mo storage. Kollidon 25 and HPMC-AS combinations resulted in the highest dissolution rates as well as dissolved drug amounts (30.4 ± 1.5μg/mL and 41.8 ± 1.7μg/mL) which in turn was 2-fold and 1.3-fold increase compared to film casted amorphous reference formulations, resp. This phenomenon also translated into a faster onset of the drug absorption in-vivo, with significantly lower tmax values, while AUC values were non-significantly lowered compared to amorphous references The high porosity of SFDs led to the advantageous accelerated dissolution which also translated into faster onset of absorption in-vivo.

European Journal of Pharmaceutics and Biopharmaceutics 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 In Synthesis of 169590-42-5.

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

Wang, Yuan published the artcileCelecoxib induces adipogenic differentiation of hemangioma-derived mesenchymal stem cells through the PPAR-γ pathway in vitro and in vivo, Formula: C17H14F3N3O2S, the publication is Experimental and Therapeutic Medicine (2022), 23(6), 375, database is CAplus and MEDLINE.

Infantile hemangioma (IH) is a benign tumor that produces a permanent scar or a mass of fibro-fatty tissue after involution in 40-80% of cases. Celecoxib is an inhibitor of cyclooxygenase-2 (COX-2), and can inhibit angiogenesis and fibrosis. The present study aimed to clarify whether celecoxib is able to induce tumor regression with minimal side effects. For that purpose, the regulation of celecoxib in the involution of IH was investigated in an IH model. Hemangioma-derived mesenchymal stem cells (Hem-MSCs) were isolated from proliferating specimens, and an IH model was established by injecting these cells into nude mice. Celecoxib was administered in vitro and in vivo. Oil Red O staining and reverse transcription-quant.-PCR were used to detect the adipogenic differentiation of Hem-MSCs. Histol. anal. and immunohistochem. staining of the tumor xenografts were performed to investigate the pathol. evolution of the tumor. The results showed that celecoxib inhibited the proliferation and induced the adipogenic differentiation of Hem-MSCs in vitro. In vivo, adipocytes were only present in the celecoxib group at week 4, while a larger number of fibro- blasts and collagenous fibers could be observed in the basic fibroblast growth factor group. Therefore, celecoxib may be a potential agent used for IH treatment by inducing adipogenesis and inhibiting fibroblast formation.

Experimental and Therapeutic Medicine 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 C23H43NP2, Formula: C17H14F3N3O2S.

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