Day: November 21, 2022

Hopkins, Brian T. published the artcileDiscovery and Preclinical Characterization of BIIB091, a Reversible, Selective BTK Inhibitor for the Treatment of Multiple Sclerosis, Quality Control of 1462286-01-6, the publication is Journal of Medicinal Chemistry (2022), 65(2), 1206-1224, database is CAplus and MEDLINE.

Multiple Sclerosis is a chronic autoimmune neurodegenerative disorder of the central nervous system (CNS) that is characterized by inflammation, demyelination, and axonal injury leading to permeant disability. In the early stage of MS, inflammation is the primary driver of the disease progression. There remains an unmet need to develop high efficacy therapies with superior safety profiles to prevent the inflammation processes leading to disability. Herein, we describe the discovery of BIIB091 (I), a structurally distinct orthosteric ATP competitive, reversible inhibitor that binds the BTK protein in a DFG-in confirmation designed to sequester Tyr-551, an important phosphorylation site on BTK, into an inactive conformation with excellent affinity. Preclin. studies demonstrated BIB091 to be a high potency mol. with good drug-like properties and a safety/tolerability profile suitable for clin. development as a highly selective, reversible BTKi for treating autoimmune diseases such as MS.

Journal of Medicinal Chemistry published new progress about 1462286-01-6. 1462286-01-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazoles, name is 4-Chloro-N-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-amine, and the molecular formula is C8H8ClN5, Quality Control of 1462286-01-6.

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

Yang, Christine published the artcileDiscovery of Benzimidazole Oxazolidinediones as Novel and Selective Nonsteroidal Mineralocorticoid Receptor Antagonists, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is ACS Medicinal Chemistry Letters (2015), 6(4), 461-465, database is CAplus and MEDLINE.

Elaboration of the oxazolidinedione series led to replacement of the exocyclic amides with substituted benzimidazoles. The structure-activity relationship exploration resulted in the discovery of potent and selective nonsteroidal mineralocorticoid receptor antagonists with significantly improved microsomal stability and pharmacokinetic profile relative to the HTS hit. One compound I possessed comparable efficacy as spironolactone at 100 mg/kg (p.o.) in the rat natriuresis model. As such, this series was validated as a lead series for further optimization.

ACS Medicinal Chemistry Letters published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C10H11NO4, Recommanded Product: 1H-Pyrazole-4-boronic acid.

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

Yang, Christine published the artcileDiscovery of Benzimidazole Oxazolidinediones as Novel and Selective Nonsteroidal Mineralocorticoid Receptor Antagonists, Formula: C3H5BN2O2, the publication is ACS Medicinal Chemistry Letters (2015), 6(4), 461-465, database is CAplus and MEDLINE.

Elaboration of the oxazolidinedione series led to replacement of the exocyclic amides with substituted benzimidazoles. The structure-activity relationship exploration resulted in the discovery of potent and selective nonsteroidal mineralocorticoid receptor antagonists with significantly improved microsomal stability and pharmacokinetic profile relative to the HTS hit. One compound I possessed comparable efficacy as spironolactone at 100 mg/kg (p.o.) in the rat natriuresis model. As such, this series was validated as a lead series for further optimization.

ACS Medicinal Chemistry Letters published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C6H13BO3, Formula: C3H5BN2O2.

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

Zhakupbekova, Aray published the artcileQuantification of trace transformation products of rocket fuel unsymmetrical dimethylhydrazine in sand using vacuum-assisted headspace solid-phase microextraction, Formula: C4H6N2, the publication is Environmental Science and Pollution Research (2022), 29(22), 33645-33656, database is CAplus and MEDLINE.

Quantification of unsym. dimethylhydrazine transformation products in solid samples is an important stage in monitoring of environmental pollution caused by heavy rockets launches. The new method for simultaneous quantification of unsym. dimethylhydrazine transformation products in sand samples using vacuum-assisted headspace solid-phase microextraction without addition of water followed by gas chromatog.-mass spectrometry is proposed. Decreasing air evacuation time from 120 to 20 s at 23°C resulted in increased responses of analytes by 25-46% and allowed obtaining similar responses as after evacuation at -30°C. The best combination of responses of analytes and their relative standard deviations (RSDs) was achieved after air evacuation of a sample (m = 1.00 g) for 20 s at 23°C, incubation for 30 min at 40°C, and 30-min extraction at 40°C by Carboxen/polydimethylsiloxane (Car/PDMS) fiber. The method was validated in terms of linearity (R²=0.9912-0.9938), limits of detection (0.035 to 3.6 ng g^-1), limits of quantification (0.12-12 ng g^-1), recovery (84-97% with RSDs 1-11%), repeatability (RSDs 3-9%), and reproducibility (RSDs 7-11%). It has a number of major advantages over existing methods based on headspace solid-phase microextraction-lower detection limits, better accuracy and precision at similar or lower cost of sample preparation The developed method was successfully applied for studying losses of analytes from open vials with model sand spiked with unsym. dimethylhydrazine transformation products. It can be recommended for anal. of trace concentrations of unsym. dimethylhydrazine transformation products when studying their transformation, migration and distribution in contaminated sand.

Environmental Science and Pollution Research published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C15H24BN3O2, Formula: C4H6N2.

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

Vetica, Fabrizio published the artcileDesymmetrization of Cyclopentenediones via Organocatalytic Cross-Dehydrogenative Coupling, Application of 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, the publication is Advanced Synthesis & Catalysis (2017), 359(21), 3729-3734, database is CAplus.

An enantioselective synthesis of cyclopentenediones bearing a pyrazole unit was achieved through an organocatalytic Michael addition/oxidation process. This desymmetrization reaction led to the desired pyrazole-cyclopentenediones with high yield and good enantioselectivities. The postulated cross-dehydrogenative coupling-mechanism was investigated via preliminary control experiments

Advanced Synthesis & Catalysis published new progress about 14580-22-4. 14580-22-4 belongs to pyrazoles-derivatives, auxiliary class Organic Pigment, name is 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, and the molecular formula is C6H3ClFNO2, Application of 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone.

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

Demont, Emmanuel H. published the artcileDiscovery of Tetrahydropyrazolopyridine as Sphingosine 1-Phosphate Receptor 3 (S1P₃)-Sparing S1P₁ Agonists Active at Low Oral Doses, COA of Formula: C3H5BN2O2, the publication is Journal of Medicinal Chemistry (2016), 59(3), 1003-1020, database is CAplus and MEDLINE.

FTY720 is the first oral small mol. approved for the treatment of people suffering from relapsing-remitting multiple sclerosis. It is a potent agonist of the S1P₁ receptor, but its lack of selectivity against the S1P₃ receptor has been linked to most of the cardiovascular side effects observed in the clinic. These findings have triggered intensive efforts toward the identification of a second generation of S1P₃-sparing S1P₁ agonists. The authors have recently disclosed a series of orally active tetrahydroisoquinoline (THIQ) compounds matching these criteria. The authors defined and implemented a strategy aiming at the discovery of selective structurally distinct follow-up agonists. This effort culminated with the identification of a series of orally active tetrahydropyrazolopyridines, e.g. I.

Journal of Medicinal Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, COA of Formula: C3H5BN2O2.

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

Sheshachalam, Avinash published the artcileThe effect of Rho drugs on mast cell activation and degranulation, Category: pyrazoles-derivatives, the publication is Journal of Leukocyte Biology (2017), 102(1), 71-81, database is CAplus and MEDLINE.

Mast cells are tissue-resident immune cells that produce potent proinflammatory mediators, which are stored in cytoplasmic granules. Stimulation triggers degranulation, a process that mobilizes granules to dock and fuse to the plasma membrane, releasing mediators. Mast cell degranulation has an important role in immunity but can also intensify inflammation and contribute to allergic disorders. Hence, it is important to understand signaling pathways that regulate mast cell degranulation. Here, we examined the role of Rho proteins in regulating mast cell activation leading to degranulation. RBL-2H3 cells and bone marrow-derived mast cells (BMMCs) were stimulated through aggregation of FcεRI receptors. Stimulated cells showed a large increase in the levels of activated Rac and, to a lesser extent, RhoA. Drugs were used to acutely inhibit the function of specific Rho proteins. The Rac inhibitor EHT-1864 and the RhoA inhibitor rhosin inhibited degranulation. Microscopic characterization showed that, upon stimulation, RBL-2H3 cells formed surface ridges that grew into large protrusions reminiscent of circular dorsal ruffles, which flattened into large lamellipodia. LysoTracker-labeled cells showed granules stream into peripheral protrusions. EHT-1864 reduced granule motility, whereas rhosin increased motility; both drugs affected the formation of peripheral protrusions. These results showed that, in response to stimuli, Rho proteins control discrete cytoskeletal remodeling processes that are needed for granule exocytosis. Rac is required to stimulate the remodeling of mast cells, triggering actin-mediated flattening of the cell periphery to create an active degranulation zone, whereas RhoA controls the streaming of highly motile granules into the active zone.

Journal of Leukocyte Biology published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C22H32O2, Category: pyrazoles-derivatives.

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

Ouyang, Zhen-zhong published the artcileDetermination of trace scandium in fly ash by calcein fluorescence spectrophotometry, Category: pyrazoles-derivatives, the publication is Yejin Fenxi (2015), 35(6), 53-56, database is CAplus.

The fluorescence reaction between calcein and scandium(III) was studied. The results showed that trace scandium(III)ions could react with calcein to form complex in NH₃·H₂O-NH₄Cl buffer solution at pH8.5in presence of surfactant Triton X-100, and the fluorescence intensity of this system was enhanced significantly. The excitation wavelength and emission wavelength was 495 nm and 520 nm, resp. The content of scandium (III)in range of 0.021-1.80μg/mL exhibited good linearity to its fluorescence intensity difference(ΔF). The equation of linear regression wasΔF=3.431+2.473ρ (μg/mL)with correlation coefficient of r=0.998 1. The detection limit was 0.021μg/mL. The interference tests indicated that most common ions did not interfere with the determination after scandium in fly ash sample was extracted and separated with 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (PMBP)-toluene. The proposed method was applied to determination of trace scandium in fly ash samples. The results were consistent with those obtained by inductively coupled plasma at. emission spectrometry (ICP-AES). The relative standard deviation(RSD, n=6)was 0.57%-1.0%. The recoveries were between 98% and 105%.

Yejin Fenxi published new progress about 4551-69-3. 4551-69-3 belongs to pyrazoles-derivatives, auxiliary class Benzenes, name is 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and the molecular formula is C17H14N2O2, Category: pyrazoles-derivatives.

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

Luo, Dingfeng published the artcileSynthesis of herbicide candidate through optimization of quinclorac with 3-methyl-1H-pyrazol-5-yl, Name: 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, the publication is Frontiers in Chemistry (Lausanne, Switzerland) (2021), 647472, database is CAplus and MEDLINE.

To enhance quinclorac potency, twenty-five derivatives I (R = Me, Et, Ph, PhCH₂, etc.) containing 3-methyl-1H-pyrazol-5-yl moiety were synthesized by intermediate derivatization methods. The structure of the compound I (R = Me) was determined by X-ray diffraction. The activity of these compounds was affected by a substituent on the Ph group (for compounds with aryl-containing R substituent) in the following order: electron-withdrawing group > neutral group > electron-donating group. The herbicidal activity assays showed that compounds I (R = 2-FC₆H₄) (EC₅₀ = 10.53 g/ha) and I (R = Me) (EC₅₀ = 10.37 g/ha) have an excellent inhibition effect on barnyard grass in greenhouse experiment Greenhouse safety experiment on rice exhibited almost no difference in plant height and fresh weight treated with I (R = Me) at stage 1-2-leaf of rice after 14 days but I (R = 2-FC₆H₄) had a detrimental effect. Two season field assays showed I (R = Me) herbicidal activity on barnyard grass at 150 g/ha as equal as 300 g/ha quinclorac in fields in 2019 and 2020. The study demonstrated that I (R = Me) could be further researched as a potential herbicide to control barnyard grass in fields.

Frontiers in Chemistry (Lausanne, Switzerland) published new progress about 14580-22-4. 14580-22-4 belongs to pyrazoles-derivatives, auxiliary class Organic Pigment, name is 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, and the molecular formula is C10H9ClN2O, Name: 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone.

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

Liu, Kevin K.-C. published the artcile4-Methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors, Name: (1H-Pyrazol-5-yl)boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(20), 6096-6099, database is CAplus and MEDLINE.

Pteridinones were designed based on a non-selective kinase template. Because of the uniqueness of the PI3K and mTOR binding pockets, a Me group was introduced to C-4 position of the peteridinone core to give compounds with excellent selectivity for PI3K and mTOR. This series of compounds were further optimized to improve their potency against PI3Kα and mTOR. Finally, orally active compounds with improved solubility and robust in vivo efficacy in tumor growth inhibition were identified as well.

Bioorganic & Medicinal Chemistry Letters published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C3H5BN2O2, Name: (1H-Pyrazol-5-yl)boronic acid.

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