Month: November 2022

Filgueiras, Luciano Ribeiro published the artcileLeukotriene B4 as a potential therapeutic target for the treatment of metabolic disorders, Name: [(2-Hexylcyclopentylidene)amino]thiourea, the publication is Frontiers in Immunology (2015), 515/1-515/4, database is CAplus and MEDLINE.

A review discusses the role of leukotriene B4 role in metabolic dysfunctions. By increasing MyD88 expression, LTB₄ enhances macrophage response to TLR/IL1 receptor agonists potentiating the sterile inflammation, a central event in metabolic disease progression. Furthermore, LTB₄ can amplify tissue injury by increasing reactive oxygen and nitrogen species that are known to mediate β-cell destruction, impairing insulin production Although further studies are required, inhibition of the LTB4/BLT1 axis is a promising therapeutic strategy for the treatment of metabolic disorders. It also discusses about the development of 5-LO inhibitor that is already approved to treat asthma, and BLT1 antagonists and reduction in LTB₄ production or activity may reduce sterile inflammation and decrease disease severity.

Frontiers in Immunology 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, Name: [(2-Hexylcyclopentylidene)amino]thiourea.

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

Steffek, Micah published the artcileA multifaceted hit-finding approach reveals novel LC3 family ligands, Synthetic Route of 475216-25-2, the publication is Biochemistry, database is CAplus and MEDLINE.

Autophagy-related proteins (Atgs) drive the lysosome-mediated degradation pathway, autophagy, to enable the clearance of dysfunctional cellular components and maintain homeostasis. In humans, this process is driven by the mammalian Atg8 (mAtg8) family of proteins comprising the LC3 and GABARAP subfamilies. The mAtg8 proteins play essential roles in the formation and maturation of autophagosomes and the capture of specific cargo through binding to the conserved LC3-interacting region (LIR) sequence within target proteins. Modulation of interactions of mAtg8 with its target proteins via small-mol. ligands would enable further interrogation of their function. Here we describe unbiased fragment and DNA-encoded library (DEL) screening approaches for discovering LC3 small-mol. ligands. Both strategies resulted in compounds that bind to LC3, with the fragment hits favoring a conserved hydrophobic pocket in mATG8 proteins, as detailed by LC3A-fragment complex crystal structures. Our findings demonstrate that the malleable LIR-binding surface can be readily targeted by fragments; however, rational design of addnl. interactions to drive increased affinity proved challenging. DEL libraries, which combine small, fragment-like building blocks into larger scaffolds, yielded higher-affinity binders and revealed an unexpected potential for reversible, covalent ligands. Moreover, DEL hits identified possible vectors for synthesizing fluorescent probes or bivalent mols. for engineering autophagic degradation of specific targets.

Biochemistry published new progress about 475216-25-2. 475216-25-2 belongs to amides-buliding-blocks, auxiliary class Fluoride,Nitro Compound,Amine,Benzene,Amide,Benzene Compounds, name is 4-Fluoro-N-methyl-3-nitrobenzamide, and the molecular formula is C9H13NO2, Synthetic Route of 475216-25-2.

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

Hudson, Robert H. E. published the artcileOn the Necessity of Nucleobase Protection for 2-Thiouracil for Fmoc-Based Pseudo-Complementary Peptide Nucleic Acid Oligomer Synthesis, HPLC of Formula: 186046-83-3, the publication is Journal of Organic Chemistry (2019), 84(21), 13252-13261, database is CAplus and MEDLINE.

A selection of benzyl-based protecting groups for thiouracil (^SU) for use in in pseudo-complementary peptide nucleic acid (PNA) have been evaluated. The 4-methoxybenzyl protecting group that has found use for ^SU during Boc-based (Boc = tert-butoxycarbonyl) oligomerization is also suitable for Fmoc-based (Fmoc = 9-fluorenylmethoxycarbonyl) oligomerization. Furthermore, it is demonstrated that ^SU protection is unnecessary for the successful synthesis of thiouracil-containing PNA. The rate of acidolysis of the 4-methoxybenzyl protecting group is compared to the recently reported 2-methyl-4-methoxybenzyl group and to the hyper labile the 2,4-dimethoxybenzyl group as well as the surprisingly resistant 2-methoxybenzyl group. The 2-thiothymine (^ST) PNA monomer has also been prepared and incorporated into an oligomer. In the sequence context examined, the ^ST insert resulted in a mild destabilization (ΔTm = -1.0/insert) relative to T, whereas ^SU had a slight stabilizing effect (ΔTm = +0.3/insert).

Journal of Organic Chemistry published new progress about 186046-83-3. 186046-83-3 belongs to amides-buliding-blocks, auxiliary class Purine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid, and the molecular formula is C40H35N7O8, HPLC of Formula: 186046-83-3.

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

Voordes, Geert H. D. published the artcileThe interplay between sacubitril/valsartan, heart failure with preserved ejection fraction, diabetes and kidney function, Category: amides-buliding-blocks, the publication is European Journal of Heart Failure (2022), 24(5), 804-806, database is CAplus and MEDLINE.

A review. This article refers to ‘Effects of sacubitril/valsartan vs. valsartan on renal function in patients with and without diabetes and heart failure with preserved ejection fraction: insights from PARAGON-HF’ by A. Peikert et al. , published in this issue on pages 794-803. Two important clin. points can be taken from this study. First, based on the available data sacubitril/valsartan has a similar renoprotective effect in patients with HFpEF with and without DM. Second, sacubitril/valsartan might represent a valuable treatment option for patients with HFpEF and diabetes to attenuate kidney function decline.

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 C9H5ClO4S, Category: amides-buliding-blocks.

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

Bray, Leslie D. published the artcileHydrolysis of prosulfuron at pH 5: evidence for a resonance-stabilized triazine cleavage product, HPLC of Formula: 94125-42-5, the publication is Pesticide Science (1997), 51(1), 56-64, database is CAplus.

Prosulfuron is a herbicide for the selective control of broadleaf weeds in corn. In order to exam. the effect of pH on the stability of prosulfuron in aqueous solution, a hydrolysis experiment was conducted in buffer at pH 5, 7 and 9 utilizing [phenyl-¹⁴C] and [triazine-¹⁴C]prosulfuron. Prosulfuron was found to be stable under neutral and basic conditions and hydrolytically unstable under acidic conditions (T_1/2 ∼ 10 days). One of the major routes of degradation at pH 5 involved hydrolysis of the sulfonylurea bridge to yield the corresponding phenyl- and triazine-cleavage products and minor amounts of desmethyl-prosulfuron and dihydroxymethyltriazine. In addition to these hydrolysis products, an unknown species was observed at significant levels after 30 days (∼20% of the applied dose). A large-scale experiment was subsequently performed to generate addition material for the spectroscopic characterization and identification of this unknown degradate. A thorough spectral evaluation of this unknown revealed a resonance-stabilized derivative of the parent mol. which stemmed from a hydrolytic opening of the triazine ring of desmethyl-prosulfuron. Although this triazine ring-opening phenomenon was first described for chlorsulfuron, a structurally related sulfonylurea herbicide, the structure of the product was only postulated. Recently, Cambon et al. described the hydrolysis kinetics of thifensulfuron and thifensulfuron-Me which resulted in cleavage of the sulfonylurea bridge and triazine ring-opening. The results support these findings and the characterization and identification of this resonance-stabilized species were described by comparison with the recently synthesized authentic reference standard

Pesticide Science published new progress about 94125-42-5. 94125-42-5 belongs to amides-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Sulfamide,Amine,Benzene, name is 2-(3,3,3-Trifluoropropyl)benzenesulfonamide, and the molecular formula is C9H10F3NO2S, HPLC of Formula: 94125-42-5.

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

Todaro, V. published the artcileDevelopment and characterization of ibuprofen co-crystals granules prepared via fluidized bed granulation in a one-step process – a design of experiment approach, Safety of Isonicotinamide, the publication is Drug Development and Industrial Pharmacy (2021), 47(2), 292-301, database is CAplus and MEDLINE.

The focus of this study was to investigate the possibility of producing ibuprofen-nicotinamide (IBU-NIC) and ibuprofen-isonicotinamide (IBU-INA) cocrystal-containing granules, using a one-step fluidized bed dryer granulation manufacturing process, and evaluate their mech. properties. Pharmaceutical cocrystals represent a suitable strategy to improve properties of active pharmaceutical ingredients (APIs), such as solubility and processability. Ibuprofen (IBU) is a small mol. API which can form cocrystals with different coformers, including NIC and INA. An improvement in mech. properties for IBU-NIC cocrystals relative to IBU was previously reported but, to date, the formulation of IBU cocrystals in a solid dosage form has not been investigated. In situ cocrystn. and granulation were achieved concurrently by processing in a lab-scale fluidized bed granulator following a design of experiment (DoE) approach using a two-level factorial design with both process and formulation variables. Solid-state, micrometric, dissolution, and mech. (tabletability) characteristics of granules were assessed post-processing. Granules containing cocrystals were successfully prepared for 11 of 16 DoE runs. Parameters with a significant effect on granule drug loading, flow function, porosity, and size could be identified from the DoE model. Process yield was increased by using a high inlet temperature at high solution feed rate. To avoid the formation of sticky particles, caking and over-wetting of the powder during the process, the utilization of high inlet temperature, low API + coformer:filler ratio, low API concentration in solution and low solution feed rate were suggested by the model. The multivariable model developed enables accurate optimization of the granulation process for IBU cocrystals.

Drug Development and Industrial Pharmacy published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C5H11BrO, Safety of Isonicotinamide.

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

Wen, Xiaoting published the artcileHydration of Nitriles Enabled by PNP-manganese Pincer Catalyst, Recommanded Product: Isonicotinamide, the publication is Asian Journal of Organic Chemistry (2022), 11(4), e202100781, database is CAplus.

A general and practical methodol. for the hydration of nitriles to primary amides enabled by manganese catalyst was presented. The described protocol showed broad substrate scope with good functional group tolerance, including a wide range of (hetero)aromatic and aliphatic nitriles, thus afforded the corresponding amides RC(O)NH₂ [R = c-hexyl, Ph, 2-furyl., etc.] in good to excellent isolated yields under mild conditions. Preliminary mechanistic studies indicated that metal-ligand cooperation (MLC) mode was involved in this catalytic process.

Asian Journal of Organic Chemistry published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C8H11NO, Recommanded Product: Isonicotinamide.

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

Zhang, Mengyuan published the artcilePlaque-hyaluronidase-responsive high-densitylipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy, Recommanded Product: [(2-Hexylcyclopentylidene)amino]thiourea, the publication is International Journal of Nanomedicine (2017), 533-558, database is CAplus and MEDLINE.

Increasing evidence has highlighted the pivotal role that intimal macrophage (iMΦ) plays in the pathophysiol. of atherosclerotic plaques, which represents an attractive target for atherosclerosis treatment. In this work, to address the insufficient specificity of conventional reconstituted high-d. lipoprotein (rHDL) for iMΦ and its limited cholesterol efflux ability, we designed a hyaluronan (HA)-anchored core-shell rHDL. This nanoparticle achieved efficient iMΦ-targeted drug delivery via a multistage-targeting approach, and excellent cellular cholesterol removal. It contained a biodegradable poly (lactic-co-glycolic acid) (PLGA) core within a lipid bilayer, and apolipoprotein A-I (apoA-I) absorbing on the lipid bilayer was covalently decorated with HA. The covalent HA coating with superior stability and greater shielding was favorable for not only minimizing the liver uptake but also facilitating the accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors in atherosclerotic plaques. The ultimate iMΦ homing was achieved via apoA-I after HA coating degraded by hyaluronidase (HAase) (abundant in atherosclerotic plaque). The multistage-targeting mechanism was revealed on the established injured endothelium-macrophage co-culture dynamic system. Upon treatment with HAase in vitro, the nanoparticle HA-(C)-PLGA-rHDL exhibited a greater cholesterol efflux capacity compared with conventional rHDL (2.43-fold). Better targeting efficiency toward iMΦ and attenuated liver accumulation were further proved by results from ex vivo imaging and iMΦ-specific fluorescence localization. Ultimately, HA-(C)-PLGA-rHDL loaded with simvastatin realized the most potent anti-atherogenic efficacies in model animals over other preparations Thus, the HAase-responsive HDL-mimetic nanoparticle was shown in this study to be a promising nanocarrier for anti-atherogenic therapy, in the light of efficient iMΦ-targeted drug delivery and excellent function of mediating cellular cholesterol efflux.

International Journal of Nanomedicine 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 C8H8O3, Recommanded Product: [(2-Hexylcyclopentylidene)amino]thiourea.

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