Category: amides-buliding-blocks

Jiang, Wenxiao published the artcileEffects of Different Nonsteroidal Anti-Inflammatory Drugs Combined with Platelet-Rich Plasma on Inflammatory Factor Levels in Patients with Osteoarthritis., Computed Properties of 169590-42-5, the publication is Journal of healthcare engineering (2022), 1979892, database is MEDLINE.

Objective: To investigate the effects of different nonsteroidal anti-inflammatory drugs combined with platelet-rich plasma on inflammatory factor levels in patients with osteoarthritis. Methods: The clinic data of 120 patients with osteoarthritis who were treated in our hospital (June 2019-June 2021) were retrospectively reviewed. All the patients were given platelet-rich plasma. According to the different nonsteroidal anti-inflammatory drugs the patients received, they were equalized into diclofenac sodium group, celecoxib group, and iguratimod group, with 40 cases in each group. After treatment, the patients’ clinical efficacy was compared and analyzed. Results: After treatment, the pain degrees of the patients in the three groups were gradually reduced. After 4 weeks and 8 weeks of treatment, the statistical differences in the scores of Visual Analogue Scale (VAS) were found among the three groups. Specifically, compared with the other two groups, the iguratimod group had remarkably lower VAS scores (P < 0.05) and the celecoxib group had signally lower VAS scores compared with the diclofenac sodium group (P < 0.05). After treatment, the inflammatory factor levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) in the diclofenac sodium group were observably higher compared with the celecoxib group (P < 0.05), and the inflammatory factor levels in the celecoxib group were remarkably higher compared with the iguratimod group (P < 0.05). Before treatment, no notable difference in the Lysholm scores was found among the three groups, and the patients’ knee joint function was gradually improved after treatment. To be specific, after 4 and 8 weeks of treatment, the iguratimod group had observably higher Lysholm scores compared with the other two groups (P < 0.05), and the celecoxib group had signally higher Lysholm scores compared with the diclofenac sodium group (P < 0.05). The iguratimod group got markedly lower Western Ontario and McMaster Universities (WOMAC) score compared with the celecoxib group (P < 0.05); Compared with the diclofenac sodium group, the celecoxib group got remarkably lower WOMAC score (P < 0.05). During treatment, few patients suffered from mild gastrointestinal discomfort and hepatic dysfunction in the three groups, and no other severe adverse reactions were found. No statistical difference in the total incidence of adverse reactions among the three groups was observed (P > 0.05). Conclusion: The combination of nonsteroidal anti-inflammatory drugs with platelet-rich plasma can further reduce the inflammatory reactions of the patients with osteoarthritis and improve their knee joint function. Significantly, the iguratimod, with high safety, has observably better effects on inhibiting inflammatory factors and improving knee joint function compared with diclofenac sodium and celecoxib.

Journal of healthcare engineering 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

Teng, Fan published the artcileA copper-mediated oxidative N-cyanation reaction, COA of Formula: C15H14N2, the publication is Chemical Communications (Cambridge, United Kingdom) (2014), 50(61), 8412-8415, database is CAplus and MEDLINE.

Copper-promoted N-cyanation of aliphatic sec-amine by CuCN is achieved via oxidative coupling. This procedure employs O₂ as a clean oxidant. Notably, sulfoximines and 1,1,3,3-tetramethylguanidine also worked well in this procedure. Thus, it represents a key progress in the C-N bond formation reaction as well as in the cyanation reaction.

Chemical Communications (Cambridge, United Kingdom) 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 C13H9FO2, COA of Formula: C15H14N2.

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

Zhang, Rui-Bo published the artcileDesign, Synthesis, and Molecular Mechanism Studies of N-Phenylisoxazoline-thiadiazolo[3,4-a]pyridazine Hybrids as Protoporphyrinogen IX Oxidase Inhibitors, Synthetic Route of 372136-76-0, the publication is Journal of Agricultural and Food Chemistry (2020), 68(47), 13672-13684, database is CAplus and MEDLINE.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an important target for green agrochem. discovery. Herein, a novel N-phenylisoxazoline-thiadiazolo[3,4-a]pyridazine herbicidal active scaffold was designed by the scaffold hybridization strategy. Systematic structural optimization enabled the discovery of a series of derivatives with excellent weed control at 9.375-150 g ai/ha by the post-emergent application. Some derivatives exhibited improved Nicotiana tabacum PPO (NtPPO)-inhibitory activity than fluthiacet-Me. Of these, I, with K_i = 21.8 nM, displayed higher weed control than fluthiacet-Me at the rate of 12-75 g ai/ha, and selective to maize at 75 g ai/ha. In planta, I was converted into a bioactive metabolite II (K_i = 4.6 nM), which exhibited 4.6-fold more potency than I in inhibiting the activity of NtPPO. Mol. dynamics simulation explained that II formed stronger π-π interaction with Phe392 than that of I. This work not only provides a promising lead compound for weed control in maize fields but is also helpful to understand the mol. mechanism and basis of the designed hybrids.

Journal of Agricultural and Food Chemistry published new progress about 372136-76-0. 372136-76-0 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Amine,Aliphatic hydrocarbon chain, name is N-Methyl-N-isopropylsulfamoyl amide, and the molecular formula is C38H74Cl2N2O4, Synthetic Route of 372136-76-0.

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

Wang, Ruifeng published the artcileDesign, synthesis, biological evaluation and molecular docking study of novel thieno[3,2-d]pyrimidine derivatives as potent FAK inhibitors, Formula: C14H20BNO3, the publication is European Journal of Medicinal Chemistry (2020), 112024, database is CAplus and MEDLINE.

A series of 2,7-disubstituted thieno[3,2-d]pyrimidine derivatives I [R¹ = 2-methoxy, 3-acetyl, 3-methylsulfonyl, etc.], II [R² = methylcarbamoyl, piperidine-3-carbonylamino, diethoxyphosphorylmethyl, etc.], III [R³ = H, Me, ethoxy, etc.; R⁴ = H, fluoro, methyl; R⁵ = H, fluoro] and IV [R⁶ = pyrrolidin-3-yl, tetrahydro-2H-pyran-4-yl, piperidin-3-ylmethyl, etc.] were synthesized and evaluated as novel focal adhesion kinase (FAK) inhibitors. The novel 2,7-disubstituted thieno[3,2-d]pyrimidine scaffold was designed as a new kinase inhibitor platform that mimics the bioactive conformation of the well-known diaminopyrimidine motif. Most of the compounds potently suppressed the enzymic activities of FAK and potently inhibited the proliferation of U-87MG, A-549 and MDA-MB-231 cancer cell lines. Among these derivatives, the optimized compound III [R³ = R⁵ = H, R⁴ = fluoro] potently inhibited the enzyme (IC₅₀ = 28.2 nM) and displayed stronger potency than TAE-226 in U-87MG, A-549 and MDA-MB-231 cells, with IC₅₀ values of 0.16, 0.27, and 0.19μM, resp. Compound III [R³ = R⁵ = H, R⁴ = fluoro] also exhibited relatively less cytotoxicity (IC₅₀ = 3.32μM) toward a normal human cell line, HK2. According to the flow cytometry results, compound III [R³ = R⁵ = H, R⁴ = fluoro] induced the apoptosis of MDA-MB-231 cells in a dose-dependent manner and effectively arrested MDA-MB-231 cells in G0/G1 phase. Further investigations revealed that compound III [R³ = R⁵ = H, R⁴ = fluoro] potently suppressed the migration of MDA-MB-231 cells. Collectively, these data support the further development of compound III [R³ = R⁵ = H, R⁴ = fluoro] as a lead compound for FAK-targeted anticancer drug discovery.

European 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 C10H15ClO3S, Formula: C14H20BNO3.

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

Qiu, Xinyi published the artcileRemodeling the periodontitis microenvironment for osteogenesis by using a reactive oxygen species-cleavable nanoplatform, Computed Properties of 1869-45-0, the publication is Acta Biomaterialia (2021), 593-605, database is CAplus and MEDLINE.

Modestly removing the excessive reactive oxygen species (ROS) plays a crucial role in regulating the microenvironment of periodontitis and provides favorable conditions for osteogenesis. However, the current strategy for scavenging ROS is not controllable, substantially limiting the outcomes in periodontitis. Herein, we introduced a controllable ROS-scavenging nanoplatform by encasing N-acetylcysteine NAC, (a well-known ROS scavenger) into tailor-made ROS-cleavable amphiphilic polymer nanoparticles (PEG-ss-PCL NPs) as an intracellular delivery carrier. The existing ROS in the inflammatory microenvironment facilitated polymer degradation via breakage of thioketal bonds, and then led to encapsulated NAC release. NAC eliminated all ROS induced by lipopolysaccharide (LPS), while PssL-NAC adjusted the ROS level slightly higher than that of the control group. The percentage of apoptotic cells cultured with NAC and PssL-NAC decreased observably compared with that of cells cultured with 10 Μg/mL LPS. The microenvironment regulated by PssL-NAC was highly suitable for osteogenic differentiation based on PCR and Western blot results, which showed higher expression levels of BMP2, Runx2, and PKA. Anal. of ALP activity and Alizarin red S staining showed consistent results. Addnl., the injection of PssL-NAC into the periodontitis area could alleviate the tissue destruction induced by ligation of the maxillary second molar. PssL-NAC showed a better ability to decrease osteoclast activity and inflammation, consequently improving the restoration of destroyed tissue. Our study suggests that ROS-responsive polymer nanoparticles loaded with NAC (PssL-NAC) can be new promising materials for the treatment of periodontitis. More and more studies indicate that periodontal tissue damage is closely related to the high reactive oxygen species (ROS) environment. Excessive ROS will aggravate periodontal tissue damage and is not conducive to tissue repair. However, as an essential signal mol. in human physiol. activities, ROS absence is also useless for tissue repair. In this study, we proposed to improve ROS imbalance in the environment of periodontitis as a strategy to promote periodontal regeneration and successfully synthesized a smart drug-releasing nanoplatform that can respond to ROS. Besides, we validated its ability to regulate the ROS environment and promote osteogenesis through exptl. data in vivo and in vitro.

Acta Biomaterialia published new progress about 1869-45-0. 1869-45-0 belongs to amides-buliding-blocks, auxiliary class Trifluoromethylated Building Blocks, name is 2,2,2-Trifluoro-N-(2-mercaptoethyl)acetamide, and the molecular formula is C4H6F3NOS, Computed Properties of 1869-45-0.

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

Liu, Hong-ming published the artcileA bifunctional enzyme belonging to cytochrome P450 family involved in the O-dealkylation and N-dealkoxymethylation toward chloroacetanilide herbicides in Rhodococcus sp. B2, Recommanded Product: 2-Chloroacetamide, the publication is Microbial Cell Factories (2021), 20(1), 61, database is CAplus and MEDLINE.

The chloroacetamide herbicides pretilachlor is an emerging pollutant. Due to the large amount of use, its presence in the environment threatens human health. However, the mol. mechanism of pretilachlor degradation remains unknown. Now, Rhodococcus sp. B2 was isolated from rice field and shown to degrade pretilachlor. The maximum pretilachlor degradation efficiency (86.1%) was observed at a culture time of 5 d, an initial substrate concentration 50 mg/L, pH 6.98, and 30.1 °C. One novel metabolite N-hydroxyethyl-2-chloro-N-(2, 6-diethyl-phenyl)-acetamide was identified by gas chromatog.-mass spectrometry (GC-MS). Draft genome comparison demonstrated that a 32,147-bp DNA fragment, harboring gene cluster (EthRABCDB2), was absent from the mutant strain TB2 which could not degrade pretilachlor. The Eth gene cluster, encodes an AraC/XylS family transcriptional regulator (EthRB2), a ferredoxin reductase (EthAB2), a cytochrome P 450 monooxygenase (EthBB2), a ferredoxin (EthCB2) and a 10-kDa protein of unknown function (EthDB2). Complementation with EthABCDB2 and EthABDB2, but not EthABCB2 in strain TB2 restored its ability to degrade chloroacetamide herbicides. Subsequently, codon optimization of EthABCDB2 was performed, after which the optimized components were sep. expressed in Escherichia coli, and purified using Ni-affinity chromatog. A mixture of EthABCDB2 or EthABDB2 but not EthABCB2 catalyzed the N-dealkoxymethylation of alachlor, acetochlor, butachlor, and propisochlor and O-dealkylation of pretilachlor, revealing that EthDB2 acted as a ferredoxin in strain B2. EthABDB2 displayed maximal activity at 30 °C and pH 7.5. This is the first report of a P 450 family oxygenase catalyzing the O-dealkylation and N-dealkoxymethylation of pretilachlor and propisochlor, resp. And the results of the present study provide a microbial resource for the remediation of chloroacetamide herbicides-contaminated sites. The GenBank accession numbers of the Rhodococcus sp. B2 16S rRNA gene, sequence of the gene cluster EthRABCD B2 and scaffold 51 are KM875453, KJ946935 and MW378985.

Microbial Cell Factories published new progress about 79-07-2. 79-07-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Aliphatic hydrocarbon chain,Amide,Inhibitor, name is 2-Chloroacetamide, and the molecular formula is C2H4ClNO, Recommanded Product: 2-Chloroacetamide.

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

Zhang, Yue published the artcileAngiotensin receptor-neprilysin inhibitor attenuates cardiac hypertrophy and improves diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction, Synthetic Route of 137862-53-4, the publication is Clinical and Experimental Pharmacology and Physiology (2022), 49(8), 848-857, database is CAplus and MEDLINE.

LCZ696, an angiotensin receptor-neprilysin inhibitor, has shown promising clin. efficacy in patients with heart failure (HF) with reduced ejection fraction. However, its potential effects on heart failure with preserved ejection fraction (HFpEF) are still not fully understood. We evaluated the effect of LCZ696 on HFpEF in transverse aortic constriction mice and compared it with the effect of the angiotensin receptor blocker, valsartan. We found that LCZ696 improved cardiac diastolic function by reducing ventricular hypertrophy and fibrosis in mice with overload-induced diastolic dysfunction. In addition, there was superior inhibition of LCZ696 than stand-alone valsartan. As a potential underlying mechanism, we demonstrated that LCZ696 behaves as a potent suppressor of calcium-mediated calcineurin-nuclear factor of activated T cells (NFAT) signalling transduction pathways. Hence, we demonstrated the protective effects of LCZ696 in overload-induced HFpEF and provided a pharmaceutical therapeutic strategy for related diseases.

Clinical and Experimental Pharmacology and Physiology 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 C17H19N3O7S, Synthetic Route of 137862-53-4.

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

Chen, Zimin published the artcileN-Cyanation of Primary and Secondary Amines with Cyanobenziodoxolone (CBX) Reagent, Product Details of C15H14N2, the publication is Chemistry – A European Journal (2021), 27(60), 14836-14840, database is CAplus and MEDLINE.

An efficient electrophilic N-cyanation of amines e.g., pyrrolidine with a stable and less-toxic 1-cyano-1,2-benziodoxol-3-(1H)-one reagent towards the synthesis of cyanamides e.g., Pyrrolidine-1-carbonitrile was disclosed. This synthetically practicable strategy allows the construction of a wide variety of cyanamides under very mild and simple conditions with a broad functional group compatibility, and showcases a huge potential in late-stage modification of complex mols.

Chemistry – A European Journal 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 C15H14N2, Product Details of C15H14N2.

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

Ibrahim, Ayon published the artcileLocal Mitochondrial ATP Production Regulates Endothelial Fatty Acid Uptake and Transport, Name: N-((4-Acetamidophenyl)carbamothioyl)-4-(tert-butyl)benzamide, the publication is Cell Metabolism (2020), 32(2), 309-319.e7, database is CAplus and MEDLINE.

Most organs use fatty acids (FAs) as a key nutrient, but little is known of how blood-borne FAs traverse the endothelium to reach underlying tissues. We conducted a small-mol. screen and identified niclosamide as a suppressor of endothelial FA uptake and transport. Structure/activity relationship studies demonstrated that niclosamide acts through mitochondrial uncoupling. Inhibitors of oxidative phosphorylation and the ATP/ADP translocase also suppressed FA uptake, pointing principally to ATP production Decreasing total cellular ATP by blocking glycolysis did not decrease uptake, indicating that specifically mitochondrial ATP is required. Endothelial FA uptake is promoted by fatty acid transport protein 4 (FATP4) via its ATP-dependent acyl-CoA synthetase activity. Confocal microscopy revealed that FATP4 resides in the endoplasmic reticulum (ER), and that endothelial ER is intimately juxtaposed with mitochondria. Together, these data indicate that mitochondrial ATP production, but not total ATP levels, drives endothelial FA uptake and transport via acyl-CoA formation in mitochondrial/ER microdomains.

Cell Metabolism 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

Mochizuki, Tatsuki published the artcileEffect of Cyclosporin A and Impact of Dose Staggering on OATP1B1/1B3 Endogenous Substrates and Drug Probes for Assessing Clinical Drug Interactions, Application of (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is Clinical Pharmacology & Therapeutics (Hoboken, NJ, United States) (2022), 111(6), 1315-1323, database is CAplus and MEDLINE.

This study was designed to assess the quant. performance of endogenous biomarkers for organic anion transporting polypeptide (OATP) 1B1/1B3-mediated drug-drug interactions (DDIs). Ten healthy volunteers orally received OATP1B1/1B3 probe cocktail (0.2 mg pitavastatin, 1 mg rosuvastatin, and 2 mg valsartan) and an oral dose of cyclosporin A (CysA, 20 mg and 75 mg) separated by a 1-h interval (20 mg (-1 h), and 75 mg (-1 h)). CysA 75 mg was also given with a 3-h interval (75 mg (-3 h)) to examine the persistence of OATP1B1/1B3 inhibition. The area under the plasma concentration-time curve ratios (AUCRs) were 1.63, 3.46, and 2.38 (pitavastatin), 1.39, 2.16, and 1.81 (rosuvastatin), and 1.42, 1.77, and 1.85 (valsartan), at 20 mg, 75 mg (-1 h) and 75 mg (-3 h) of CysA, resp. CysA effect on OATP1B1/1B3 was unlikely to persist at the dose examined Among 26 putative OATP1B1/1B3 biomarkers evaluated, AUCR and maximum concentration ratio (C_maxR) of CP-I showed the highest Pearson′s correlation coefficient with CysA AUC (0.94 and 0.93, resp.). Correlation between AUCR of pitavastatin, and C_maxR or AUCR of CP-I were consistent between this study and our previous study using rifampicin as an OATP1B1/1B3 inhibitor. Nonlinear regression anal. of AUCR^-1 of pitavastatin and CP-I against CysA C_max yielded K_{i,OATP1B1/1B3,app} (109 ± 35 and 176 ± 42 nM, resp.), similar to the K_{i,OATP1B1/1B3} estimated by our physiol.-based pharmacokinetic model anal. described previously (107 nM). The endogenous OATP1B1/1B3 biomarkers, particularly C_maxR and AUCR of CP-I, corroborates OATP1B1/1B3 inhibition and yields valuable information that improve accurate DDI predictions in drug development, and enhance our understanding of interindividual variability in the magnitude of DDIs.

Clinical Pharmacology & Therapeutics (Hoboken, NJ, United States) 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, Application of (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