Month: November 2022

Hansen, Trond Vidar published the artcileThe novel lipid mediator PD1_n-3 DPA: An overview of the structural elucidation, synthesis, biosynthesis and bioactions, Related Products of amides-buliding-blocks, the publication is Prostaglandins and Other Lipid Mediators (2017), 103-110, database is CAplus and MEDLINE.

A review. Resolvins, protectins and maresins are individual families of specialized pro-resolving mediators biosynthesized from the dietary n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid. These enzymically oxygenated polyunsaturated lipid mediators were first elucidated during the resolution phase of acute inflammation in animal models of self-limited inflammation. Specialized pro-resolving mediators display potent bioactions when administrated in vivo. Biosynthetic pathway studies have revealed that individual lipoxygenases and cyclooxygenase-2 converts eicosapentaenoic acid and docosahexaenoic acid into distinct families of the resolvins, protectins and maresins. Recently n-3 docosapentaenoic acid was found to be a substrate for the biosynthesis of several novel families of specialized pro-resolving mediators. One example is PD1_n-3 DPA. During the 6th European Workshop on Lipid Mediators, Frankfurt, Germany, the structural elucidation, total organic synthesis, studies on the biosynthetic pathway, as well as the potent anti-inflammatory and pro-resolving properties of PD1_n-3 DPA were presented. Herein, we provide an overview of these topics for the new member PD1_n-3 DPA of the super-family of pro-resolving mediators.

Prostaglandins and Other Lipid Mediators published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, Related Products of amides-buliding-blocks.

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

Morgan, Charles W. published the artcileSelective CRAF Inhibition Elicits Transactivation, Product Details of C11H22N2O4, the publication is Journal of the American Chemical Society (2021), 143(12), 4600-4606, database is CAplus and MEDLINE.

Discovering mols. that regulate closely related protein isoforms is challenging, and in many cases the consequences of isoform-specific pharmacol. regulation remains unknown. RAF isoforms are commonly mutated oncogenes that serve as effector kinases in MAP kinase signaling. BRAF/CRAF heterodimers are believed to be the primary RAF signaling species, and many RAF inhibitors lead to a “paradoxical activation” of RAF kinase activity through transactivation of the CRAF protomer; this leads to resistance mechanisms and secondary tumors. It has been hypothesized that CRAF-selective inhibition might bypass paradoxical activation, but no CRAF-selective inhibitor has been reported and the consequences of pharmacol. inhibiting CRAF have remained unknown. Here, we use bio-orthogonal ligand tethering (BOLT) to selectively target inhibitors to CRAF. Our results suggest that selective CRAF inhibition promotes paradoxical activation and exemplify how BOLT may be used to triage potential targets for drug discovery before any target-selective small mols. are known.

Journal of the American Chemical Society 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 C11H22N2O4, Product Details of C11H22N2O4.

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

Zhao, Qiuying published the artcilePrenatal disruption of blood-brain barrier formation via cyclooxygenase activation leads to lifelong brain inflammation, Recommanded Product: 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Proceedings of the National Academy of Sciences of the United States of America (2022), 119(15), e2113310119, database is CAplus and MEDLINE.

Gestational maternal immune activation (MIA) in mice induces persistent brain microglial activation and a range of neuropathologies in the adult offspring. Although long-term phenotypes are well documented, how MIA in utero leads to persistent brain inflammation is not well understood. Here, we found that offspring of mothers treated with polyriboinosinic-polyribocytidylic acid [poly(I:C)] to induce MIA at gestational day 13 exhibit blood-brain barrier (BBB) dysfunction throughout life. Live MRI in utero revealed fetal BBB hyperpermeability 2 d after MIA. Decreased pericyte-endothelium coupling in cerebral blood vessels and increased microglial activation were found in fetal and 1- and 6-mo-old offspring brains. The long-lasting disruptions result from abnormal prenatal BBB formation, driven by increased proliferation of cyclooxygenase-2 (COX2; Ptgs2)-expressing microglia in fetal brain parenchyma and perivascular spaces. Targeted deletion of the Ptgs2 gene in fetal myeloid cells or treatment with the inhibitor celecoxib 24 h after immune activation prevented microglial proliferation and disruption of BBB formation and function, showing that prenatal COX2 activation is a causal pathway of MIA effects. Thus, gestational MIA disrupts fetal BBB formation, inducing persistent BBB dysfunction, which promotes microglial overactivation and behavioral alterations across the offspring life span. Taken together, the data suggest that gestational MIA disruption of BBB formation could be an etiol. contributor to neuropsychiatric disorders.

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 C8H11BO2, 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

Abd-Eldayem, Ahmed M. published the artcileCelecoxib has Preventive and Therapeutic Benefits against Nephrotoxicity Caused by Gentamicin in Mice, Formula: C17H14F3N3O2S, the publication is Drug Research (Stuttgart, Germany) (2022), 72(5), 259-267, database is CAplus and MEDLINE.

It’s crucial to comprehend the impact of oxidative stress and pro-inflammatory cytokines in the gentamicin-induced kidney injury mechanism. Celecoxib was administered orally either before or after i.p. therapy with gentamicin in mice. The serum levels of creatinine (SCr), blood urea nitrogen (BUN), IL-6, and TNF-α were measured by ELISA test, as well as the levels of the kidney tissue malondialdehyde (MDA), and glutathione (GSH) were also estimated spectrophotometrically. The renal expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase 2 (COX-2) mRNAs were evaluated by qPCR. Histopathol. evaluation and Immunohistochem. examination of kidney NF-κB, IL-6, and COX-2 were also, performed. Celecoxib successfully prevented gentamicin-induced kidney damage as indicated by reducing blood BUN, SCr, and tissue MDA levels and increasing renal tissue GSH levels as well as lowering the blood IL-6 and TNF-α in comparison to mice received gentamicin. Furthermore, celecoxib has inhibited COX-2, NF-κB, IL-6, and TNF-α expression in the renal tissue. It is noteworthy that celecoxib therapy after gentamicin administration brought about substantially the same results as celecoxib treatment before gentamicin injection in mice. Our results showed the role of celecoxib as a therapeutic tool for gentamicin-induced nephrotoxicity as well as raised its beneficial prophylactic role in this medical challenge by attenuating oxidative stress and inflammation.

Drug Research (Stuttgart, Germany) 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, Formula: C17H14F3N3O2S.

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

Chen, Chen published the artcileA Convenient Synthetic Method for Trisubstituted s-Triazines, Name: 2,4-Dichlorobenzamide, the publication is Journal of Organic Chemistry (1995), 60(26), 8428-30, database is CAplus.

S-Triazines bearing a variety of substituents at the 1, 3 and 5-positions are obtained in good yields by the condensation of N’-acyl-N,N-dimethylamidines with amidines or guanidines . The N’-acyl-N,N-dimethylamidines are readily prepared from amides and N,N-dimethylformamide di-Me acetal or N,N-dimethylacetamide di-Me acetal .

Journal of Organic Chemistry published new progress about 2447-79-2. 2447-79-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Benzene,Amide, name is 2,4-Dichlorobenzamide, and the molecular formula is C7H5Cl2NO, Name: 2,4-Dichlorobenzamide.

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

Mydock-McGrane, Laurel published the artcileAntivirulence C-Mannosides as Antibiotic-Sparing, Oral Therapeutics for Urinary Tract Infections, SDS of cas: 1197171-76-8, the publication is Journal of Medicinal Chemistry (2016), 59(20), 9390-9408, database is CAplus and MEDLINE.

Gram-neg. uropathogenic Escherichia coli (UPEC) bacteria are a causative pathogen of urinary tract infections (UTIs). Previously developed antivirulence inhibitors of the type 1 pilus adhesin, FimH, demonstrated oral activity in animal models of UTI but were found to have limited compound exposure due to the metabolic instability of the O-glycosidic bond (O-mannosides). Herein, we disclose that compounds having the O-glycosidic bond replaced with carbon linkages had improved stability and inhibitory activity against FimH. We report on the design, synthesis, and in vivo evaluation of this promising new class of carbon-linked C-mannosides that show improved pharmacokinetic (PK) properties relative to O-mannosides. Interestingly, we found that FimH binding is stereospecifically modulated by hydroxyl substitution on the methylene linker, where the R-hydroxy isomer has a 60-fold increase in potency. This new class of C-mannoside antagonists have significantly increased compound exposure and, as a result, enhanced efficacy in mouse models of acute and chronic UTI.

Journal of Medicinal Chemistry published new progress about 1197171-76-8. 1197171-76-8 belongs to amides-buliding-blocks, auxiliary class Boronic acid and ester,Amine,Benzene,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is N-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, and the molecular formula is C14H20BNO3, SDS of cas: 1197171-76-8.

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

Pabon, Maria A. published the artcileNatriuretic peptide-based inclusion criteria in heart failure with preserved ejection fraction clinical trials: insights from PARAGON-HF, Recommanded Product: (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is European Journal of Heart Failure (2022), 24(4), 672-677, database is CAplus and MEDLINE.

Natriuretic peptides (NPs) are now routinely incorporated as key inclusion criteria in clin. trials of heart failure with preserved ejection fraction (HFpEF) as objective measures of risk. An early amendment in PARAGON-HF required all participants to have elevated NP concentrations, but some were enrolled pre-amendment, providing a unique opportunity to understand the influence of enrolment pathway in HFpEF clin. trials. Among 4796 participants in PARAGON-HF, 193 (4.0%) did not meet the final NP-based enrolment criteria (N-terminal pro-B-type natriuretic peptide >300 pg/mL for patients in sinus rhythm or >900 pg/mL for patients in atrial fibrillation/flutter). These patients had lower rates of the primary endpoint of total heart failure hospitalizations and cardiovascular death as compared with patients meeting final enrolment criteria (8.6 [6.7-11.2] events per 100 patient-years vs. 14.0 [13.4-14.7] events per 100 patient-years; p = 0.01). The rate ratio for the treatment effect comparing sacubitril/valsartan with valsartan was 0.85 (95% confidence interval 0.74-0.99; p = 0.04) in those who met final criteria. Natriuretic peptides are an important tool in HFpEF clin. trials to objectively affirm diagnoses and enrich clin. event rates.

European Journal of Heart Failure published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, Recommanded Product: (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid.

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

Kummer, David A. published the artcileIdentification and structure activity relationships of quinoline tertiary alcohol modulators of RORγt, Application of N-Methoxy-N-methylisonicotinamide, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(9), 2047-2057, database is CAplus and MEDLINE.

A high-throughput screen of the ligand binding domain of the nuclear receptor retinoic acid-related orphan receptor gamma t (RORγt) employing a thermal shift assay yielded a quinoline tertiary alc. hit. Optimization of the 2-, 3- and 4-positions of the quinoline core using structure-activity relationships and structure-based drug design methods led to the discovery of a series of modulators with improved RORγt inhibitory potency and inverse agonism properties.

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 of N-Methoxy-N-methylisonicotinamide.

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

Gao, Yu published the artcileOscillatory shear stress induces the transition of EPCs into mesenchymal cells through ROS/PKCζ/p53 pathway, Name: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is Life Sciences (2020), 117728, database is CAplus and MEDLINE.

Studies indicate that the pattern of shear stress determines the direction of endothelial progenitor cells (EPCs) differentiation. However, the mechanism remains largely unknown. Herein, we try to identify the role of oscillatory shear stress (OSS) in the transdifferentiation of EPCs into mesenchymal cells and the mechanism involved. OSS was applied to EPCs using the flow chamber system in vitro. Matrigel, Boyden chamber, and healing assay were used to observe the changes in EPCs function. EPCs transduced with Lentivirus carrying Tp53 were implanted into the arterial vessel in the balloon injured rat model, and neointimal thickening was verified by HE staining. In the meantime, OSS time-dependently decreased p53 expression in EPCs, which was partially abolished by treatment with ROS scavenger N-acetylcysteine (NAC) or protein kinase C zeta (PKCζ) inhibitor Go6983. Moreover, the p53 agonist tenovin-1 attenuated the changes of OSS-mediated the mesenchymal cell markers and EPCs function. Besides, we also found that transplanting EPCs transfected with LV-Tp53 significantly inhibited neointimal thickening and promoted reendothelialization in vivo. This study demonstrates OSS-induced EPC transdifferentiation into mesenchymal cells and ROS/PKCζ/p53 pathway play an essential role in it. It may serve as a promising therapeutic target for cardiovascular disease in the future.

Life Sciences 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, Name: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide.

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

Zhang, YaHan published the artcileA hyperbranched polymer-based water-resistant adhesive: Durable underwater adhesion and primer for anchoring anti-fouling hydrogel coating, Safety of N-(2-Amino-2-oxoethyl)acrylamide, the publication is Science China: Technological Sciences (2022), 65(1), 201-213, database is CAplus.

Direct deployment of gluing and achieving durable robust adhesion in water is challenging due to difficulty in repelling interface water. This work reports a novel hyperbranched polymer-based water-resistant adhesive (HBPBA) based on Michael addition reaction of multi-vinyl monomers with dopamine and 3-aminophenylboronic acid. Upon encountering water, the HBPBA forms coacervates whose hydrophobic chains aggregate to displace interface water, and meanwhile the catechols exposing outwards contribute to underwater adhesion. The HBPBA can strongly glue diverse substrates including PTFE, PE, PET, ceramic, Ti and stainless steel. The HBPBA can maintain stable adhesion in different environments, such as tap water, simulated sea water, PBS, and a wide range of pH solutions (pH 2 to 10) for 3 mo, supposedly due to the complexation of catechol with boronic acid. Intriguingly, HBPBA film can be bonded to the titanium surface as a primer, which firmly anchors the antifouling PNAGA-PCBAA hydrogel coating through copolymerization of remaining double bonds in HBPBA and NAGA plus CBAA. The PNAGA-PCBAA hydrogel-modified titanium is biocompatible and shows outstanding antifouling ability both in vitro and in vivo. This work proposes a new strategy for creating underwater deployable and water-resistant adhesives that may find promising applications in engineering and biomedical fields.

Science China: Technological Sciences published new progress about 2479-62-1. 2479-62-1 belongs to amides-buliding-blocks, auxiliary class Monomers,Acrylamide Monomers, name is N-(2-Amino-2-oxoethyl)acrylamide, and the molecular formula is C13H18N2, Safety of N-(2-Amino-2-oxoethyl)acrylamide.

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