Tag: M.W=350-400

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

Neogi, Tuhina published the artcileObserved efficacy and clinically important improvements in participants with osteoarthritis treated with subcutaneous tanezumab: results from a 56-week randomized NSAID-controlled study, Name: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Arthritis Research & Therapy (2022), 24(1), 78, database is CAplus and MEDLINE.

A recent phase 3 study demonstrated that treatment with tanezumab, a nerve growth factor inhibitor, or nonsteroidal anti-inflammatory drugs (NSAIDs) improves pain and phys. function in participants with moderate-to-severe osteoarthritis (OA) of the hip or knee. Here, we evaluated the time course and clin. importance of these initial efficacy findings using a mixture of primary, secondary, and post hoc endpoints. Participants on stable NSAID therapy and with a history of inadequate response to other standard OA analgesics were enrolled in an 80-wk (56-wk treatment/24-wk safety follow-up), randomized, NSAID-controlled, phase 3 study primarily designed to assess the safety of tanezumab for moderate-to-severe OA of the knee or hip. Participants received oral NSAID (twice daily naproxen, celecoxib, or diclofenac) or s.c. tanezumab (2.5mg or 5mg every 8 wk). Non-responders were discontinued at week 16. Changes from baseline in WOMAC Pain and Phys. Function, Patients Global Assessment of Osteoarthritis (PGA-OA), and average pain in the index joint were compared between tanezumab and NSAID groups over the 56-wk treatment period. Clin. meaningful response (e.g., ≥30% and ≥50% improvement in WOMAC Pain and Phys. Function), rescue medication use, and safety were also assessed. All groups improved WOMAC Pain, WOMAC Phys. Function, PGA-OA, and average pain in the index joint over the 56-wk treatment period relative to baseline. Across all groups, improvements generally occurred from the time of first assessment (week 1 or 2) to week 16 and then slightly decreased from week 16 to 24 before stabilizing from weeks 24 to 56. The magnitude of improvement and the proportion of participants achieving ≥30% and ≥50% improvement in these measures was greater (unadjusted p≤0.05) with tanezumab than with NSAID at some timepoints on or before week 16. Adverse events of abnormal peripheral sensation, prespecified joint safety events, and total joint replacement surgery occurred more frequently with tanezumab than with NSAID. Tanezumab and NSAID both provided early and sustained (up to 56 wk) efficacy relative to baseline. Improvements in pain and function were clin. meaningful in a substantial proportion of participants. Adverse events of abnormal peripheral sensation and joint safety events occurred more frequently with tanezumab than with NSAID. Trial registration: ClinicalTrials.govNCT02528188. Registered on 19 July 2015.

Arthritis Research & Therapy 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

Pearson, Caroline A. published the artcileWhen the BBB goes MIA, Application In Synthesis of 169590-42-5, the publication is Proceedings of the National Academy of Sciences of the United States of America (2022), 119(19), e2204159119, database is CAplus and MEDLINE.

A review. Epidemiol. studies implicate maternal immune activation (MIA) as a risk factor for a variety of neurodevelopmental disorders. Early MIA results in BBB disruption and inflammatory responses that lead to persistent postnatal structural and cellular defects associated with MIA, rescuable by celecoxib treatment. The findings advance our understanding of the developmental origins of MIA-associated cognitive deflicits and unveil a potential therapeutic intervention for the BBB dysfunction and chronic inflammation associated with neurodevelopmental disease. In addition, the data raise the possibility that the BBB alterations induced by MIA may also contribute to other diseases associated with chronic neuroinflammation. In this regard, MIA in the setting of the SARS-CoV-2 pandemic should alert health-care providers to this potential risk, warranting careful monitoring of the offspring in infected mothers.

Proceedings of the National Academy of Sciences of the United States of America 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

Herron, Alastair N. published the artcileδ-C-H Halogenation Reactions Enabled by a Nitrogen-Centered Radical Precursor, COA of Formula: C17H14F3N3O2S, the publication is Organic Letters (2022), 24(20), 3652-3656, database is CAplus and MEDLINE.

Herein, new hydrazonyl carboxylic acids RN(S(O)₂R¹)N=C(Me)C(O)OH (R = octyl, 2-(adamantan-1-yl)ethyl, 4-methylpentyl, etc.; R¹ = 4-methylphenyl, 4-methoxyphenyl, 4-bromophenyl, 4-(trifluoromethyl)phenyl) precursor to nitrogen-centered radicals and its application toward remote C-H fluorination and chlorination reactions of sulfonyl-protected alkyl amines R¹S(O)₂NHR² (R² = 4-fluorooctyl, 2-(2-fluorocyclobutyl)ethyl, 4-fluoro-4-methylpentyl, etc.) via 1,5-HAT were disclosed.

Organic Letters 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, COA of Formula: C17H14F3N3O2S.

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

Lin, Jialiang published the artcilePoly(lactic acid-co-glycolic acid)-based celecoxib extended-release microspheres for the local treatment of traumatic heterotopic ossification, SDS of cas: 169590-42-5, the publication is Journal of Biomaterials Applications (2022), 36(8), 1458-1468, database is CAplus and MEDLINE.

Traumatic heterotopic ossification (THO) is a serious and common clin. post-traumatic complication for which there is no effective and safe drug treatment. Routine administration of nonsteroidal anti-inflammatory drugs (NSAIDs) after injury is extensively used approach for THO. However, serious adverse events can occur in the event of an overdose of NSAIDs. In our study, we have developed a poly(lactic acid-co-glycolic acid) (PLGA) microsphere by emulsifying solvent volatilization for the prolonged slow delivery of celecoxib (CLX). Three groups of celecoxib-poly(lactic acid-co-glycolic acid) microspheres (CLX-PLGA MPs) were prepared with particle sizes of 3.75±1.28μm, 49.56±17.15μm, and 94.98±42.53μm. Meanwhile, related parameters of microspheres in each group were studied: drug loading (DL), encapsulation rate (EE), and slow-release behavior. The DL and EE of the 3 CLX-PLGA MPs did not vary significantly, and subsequently, we selected the second drug loading microspheres with a retardation period of about 70 days for subsequent experiments Moreover, cellular and animal experiments suggest that the microspheres are biocompatible and can be safely applied to localized trauma tissue. Finally, it is demonstrated that CLX-PLGA MPs have an effect on inhibiting the osteogenic differentiation of bone marrow mesenchymal stem cells and have the potential to inhibit ectopic bone formation of the THO model in Sprague-Dawley rat. Therefore, this study suggests that CLX-PLGA MPs are expected to be applied topically in the early post-traumatic period to prevent the development of THO.

Journal of Biomaterials Applications 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

Wang, Wei published the artcileScaffold Hopping Strategy to Identify Prostanoid EP4 Receptor Antagonists for Cancer Immunotherapy, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Journal of Medicinal Chemistry (2022), 65(11), 7896-7917, database is CAplus and MEDLINE.

Cancer cells can effectively suppress the natural immune response in humans, and prostaglandin E₂ (PGE₂) is a key mediator in the development of tumor cell resistance to immunotherapy. As a major contributor to PGE₂-elicited immunosuppressive activity, the EP4 receptor promotes tumor development and progression in the tumor microenvironment, and the development of selective and potent EP4 receptor antagonists should have promising potential for tumor immunotherapy. Aiming at improving the drug-like properties, a series of 4,7-dihydro-5H-thieno[2,3-c]pyran derivatives were designed and synthesized through a scaffold hopping strategy. The most promising compound 47 exhibited good EP4 antagonistic activity and excellent subtype selectivity, as well as favorable drug-like properties. It effectively suppressed the expression of multiple immunosuppression-related genes in macrophages. Meanwhile, oral administration of compound 47, alone or in combination with anti-PD-1 antibody, significantly enhanced the antitumor immune response and inhibited tumor growth in the mouse CT26 colon carcinoma model.

Journal of Medicinal 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 C7H8BClO3, 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

Ansari, Shaquib Rahman published the artcileHyperthermia-Induced In Situ Drug Amorphization by Superparamagnetic Nanoparticles in Oral Dosage Forms, Category: amides-buliding-blocks, the publication is ACS Applied Materials & Interfaces (2022), 14(19), 21978-21988, database is CAplus and MEDLINE.

Superparamagnetic iron oxide nanoparticles (SPIONs) generate heat upon exposure to an alternating magnetic field (AMF), which has been studied for hyperthermia treatment and triggered drug release. This study introduces a novel application of magnetic hyperthermia to induce amorphization of a poorly aqueous soluble drug, celecoxib, in situ in tablets for oral administration. Poor aqueous solubility of many drug candidates is a major hurdle in oral drug development. A novel approach to overcome this challenge is in situ amorphization of crystalline drugs. This method facilitates amorphization by mol. dispersion of the drug in a polymeric network inside a tablet, circumventing the phys. instability encountered during the manufacturing and storage of conventional amorphous solid dispersions. However, the current shortcomings of this approach include low drug loading, toxicity of excipients, and drug degradation Here, doped SPIONs produced by flame spray pyrolysis are compacted with polyvinylpyrrolidone and celecoxib and exposed to an AMF in solid state. A design of experiments approach was used to investigate the effects of SPION composition (Zn_0.5Fe_2.5O₄ and Mn_0.5Fe_2.5O₄), doped SPION content (10-20 wt %), drug load (30-50 wt %), and duration of AMF (3-15 min) on the degree of drug amorphization. The degree of amorphization is strongly linked to the maximum tablet temperature achieved during the AMF exposure (r = 0.96), which depends on the SPION composition and content in the tablets. Complete amorphization is achieved with 20 wt % Mn_0.5Fe_2.5O₄ and 30 wt % celecoxib in the tablets that reached the maximum temperature of 165.2 °C after 15 min of AMF exposure. Furthermore, manganese ferrite exhibits no toxicity in human intestinal Caco-2 cell lines. The resulting maximum solubility of in situ amorphized celecoxib is 5 times higher than that of crystalline celecoxib in biorelevant intestinal fluid. This demonstrates the promising capability of SPIONs as enabling excipients to magnetically induce amorphization in situ in oral dosage forms.

ACS Applied Materials & Interfaces 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, Category: amides-buliding-blocks.

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

Lain, Sonia published the artcileDiscovery, in vivo activity, and mechanism of action of a small-molecule p53 activator, HPLC of Formula: 380315-80-0, the publication is Cancer Cell (2008), 13(5), 454-463, database is CAplus and MEDLINE.

We have carried out a cell-based screen aimed at discovering small mols. that activate p53 and have the potential to decrease tumor growth. Here, we describe one of our hit compounds, tenovin-1, along with a more water-soluble analog, tenovin-6. Via a yeast genetic screen, biochem. assays, and target validation studies in mammalian cells, we show that tenovins act through inhibition of the protein-deacetylating activities of SirT1 and SirT2, two important members of the sirtuin family. Tenovins are active on mammalian cells at one-digit micromolar concentrations and decrease tumor growth in vivo as single agents. This underscores the utility of these compounds as biol. tools for the study of sirtuin function as well as their potential therapeutic interest.

Cancer Cell published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, HPLC of Formula: 380315-80-0.

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

Nikolos, Fotis published the artcileCell death-induced immunogenicity enhances chemoimmunotherapeutic response by converting immune-excluded into T-cell inflamed bladder tumors, Quality Control of 169590-42-5, the publication is Nature Communications (2022), 13(1), 1487, database is CAplus and MEDLINE.

Chemoimmunotherapy has recently failed to demonstrate significant clin. benefit in advanced bladder cancer patients; and the mechanism(s) underlying such suboptimal response remain elusive. To date, most studies have focused on tumor-intrinsic properties that render them “immune-excluded”. Here, we explore an alternative, drug-induced mechanism that impedes therapeutic response via disrupting the onset of immunogenic cell death. Using two immune-excluded syngeneic mouse models of muscle-invasive bladder cancer (MIBC), we show that platinum-based chemotherapy diminishes CD8+ T cell tumor infiltration and constraines their antitumoral activity, despite expression of activation markers IFNγ and granzyme B. Mechanistically, chemotherapy induces the release of prostaglandin E2 (PGE2) from dying cancer cells, which is an inhibitory damage-associated mol. pattern (iDAMP) that hinderes dendritic cell maturation. Upon pharmaceutical blockade of PGE2 release, CD8+ T cells become tumoricidal and display an intraepithelial-infiltrating (or inflamed) pattern. This “iDAMP blockade” approach synergizes with chemotherapy and sensitizes bladder tumors towards anti-PD1 immune checkpoint inhibitor therapy. These findings provide a compelling rationale to evaluate this drug combination in future clin. trials.

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, Quality Control of 169590-42-5.

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

Makhortova, Nina R. published the artcileA screen for regulators of survival of motor neuron protein levels, HPLC of Formula: 380315-80-0, the publication is Nature Chemical Biology (2011), 7(8), 544-552, database is CAplus and MEDLINE.

The motor neuron disease spinal muscular atrophy (SMA) results from mutations that lead to low levels of the ubiquitously expressed protein survival of motor neuron (SMN). An ever-increasing collection of data suggests that therapeutics that elevate SMN may be effective in treating SMA. The authors executed an image-based screen of annotated chem. libraries and discovered several classes of compounds that were able to increase cellular SMN. Among the most important was the RTK-PI3K-AKT-GSK-3 signaling cascade. Chem. inhibitors of glycogen synthase kinase 3 (GSK-3) and short hairpin RNAs (shRNAs) directed against this target elevated SMN levels primarily by stabilizing the protein. It was particularly notable that GSK-3 chem. inhibitors were also effective in motor neurons, not only in elevating SMN levels, but also in blocking the death that was produced when SMN was acutely reduced by an SMN-specific shRNA. Thus, the authors have established a screen capable of detecting drug-like compounds that correct the main phenotypic change underlying SMA.

Nature Chemical Biology published new progress about 380315-80-0. 380315-80-0 belongs to amides-buliding-blocks, auxiliary class Apoptosis,p53, name is N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, and the molecular formula is C20H23N3O2S, HPLC of Formula: 380315-80-0.

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