Month: November 2022

Thottacherry, Joseph Jose published the artcileMechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells, HPLC of Formula: 71203-35-5, the publication is Nature Communications (2018), 9(1), 1-14, database is CAplus and MEDLINE.

Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chem. feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells.

Nature Communications 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 C20H19NO4, HPLC of Formula: 71203-35-5.

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

Jagtap, Ajit Dhananjay published the artcile4-Substituted 2-amino-3,4-dihydroquinazolines with a 3-hairpin turn side chain as novel inhibitors of BACE-1, Recommanded Product: 1-Methylpyrazole, the publication is Bioorganic Chemistry (2020), 103135, database is CAplus and MEDLINE.

Herein, the authors report the identification, design, and synthesis of a series of 4-substituted 2-amino-3,4-dihydroquinazolines I [R¹ = Me, CH:CH₂, Bn, etc., R² = Me, cyclopropyl, (1-methyl-1H-pyrazol-4-yl)methyl] with hairpin turn side chains as novel inhibitors of BACE-1. The dihydroquinazoline derivatives were rationally designed by modifying the amide group and relocating the α-hydrophobic substituent on the hairpin turn side chain of lead compound II to the C4-position on the 3,4-dihydroquinazoline scaffold to facilitate interactions with the S₁, S₂ and S₁‘ subsites of BACE-1. Among these derivatives, two compounds exhibited potent BACE-1 inhibitory activity: 4-methyl-substituted derivative I [R¹ = Me, R² = (1-methyl-1H-pyrazol-4-yl)methyl] (BACE-1 CFA IC₅₀ = 0.38μM; BACE-1 WCA IC₅₀ = 0.14μM) and 4-cyclohexylmethyl-substituted derivative I [R¹ = cyclohexylmethyl, R² = (1-methyl-1H-pyrazol-4-yl)methyl] (BACE-1 CFA IC₅₀ = 0.49μM; BACE-1 WCA IC₅₀ = 0.14μM). The results suggest that the structural modifications maintain the hairpin turn topol. similar to that of compound II and provide an addnl. interaction with the S₂ subsite.

Bioorganic Chemistry 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 C4H6N2, Recommanded Product: 1-Methylpyrazole.

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

Petzold, Daniel published the artcilePhotocatalytic Oxidative Bromination of Electron-Rich Arenes and Heteroarenes by Anthraquinone, Category: pyrazoles-derivatives, the publication is Advanced Synthesis & Catalysis (2018), 360(4), 626-630, database is CAplus.

The estimated excited oxidation potential of sodium anthraquinone-2-sulfonate (SAS) increases from 1.8 V to ∼2.3 V vs. SCE by protonation with Bronsted acids. This increased photooxidation power of protonated anthraquinone was used for the regio-selective oxidative bromination of electron rich (hetero)arenes and drugs in good yield. The mild reaction conditions are compatible with many functional groups, such as double and triple bonds, ketones, amides and amines, hydroxyl groups, carboxylic acids and carbamates. Mechanistic studies indicate the photooxidation of the arene followed by nucleophilic bromide addition as the likely pathway.

Advanced Synthesis & Catalysis 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 C4H6N2, Category: pyrazoles-derivatives.

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

Shinozuka, Tsuyoshi published the artcileDiscovery of DS-1971a, a Potent, Selective Na_V1.7 Inhibitor, Category: pyrazoles-derivatives, the publication is Journal of Medicinal Chemistry (2020), 63(18), 10204-10220, database is CAplus and MEDLINE.

A highly potent, selective Na_V1.7 inhibitor, DS-1971a(I), has been discovered. Exploration of the left-hand Ph ring of sulfonamide derivatives (I and II) led to the discovery of novel series of cycloalkane derivatives with high Na_V1.7 inhibitory potency in vitro. As the right-hand heteroaromatic ring affected the mechanism-based inhibition liability of CYP3A4, replacement of this moiety resulted in the generation of 4-pyrimidyl derivatives Addnl., GSH adducts formation, which can cause idiosyncratic drug toxicity, was successfully avoided by this modification. An addnl. optimization led to the discovery of DS-1971a. In preclin. studies, DS-1971a demonstrated highly potent selective in vitro profile with robust efficacy in vivo. DS-1971a exhibited a favorable toxicol. profile, which enabled multiple-dose studies of up to 600 mg bid or 400 mg tid (1200 mg/day) administered for 14 days to healthy human males. DS-1971a is expected to exert potent efficacy in patients with peripheral neuropathic pain, with a favorable safety profile.

Journal of Medicinal Chemistry 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 C22H23ClN4, Category: pyrazoles-derivatives.

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

Wietelmann, Ulrich published the artcileContinuous Processing of Concentrated Organolithiums in Flow Using Static and Dynamic Spinning Disc Reactor Technologies, Name: 1-Methylpyrazole, the publication is Organic Process Research & Development (2022), 26(5), 1422-1431, database is CAplus.

Organometallic reactions involving highly reactive organolithium reagents are widely used in organic synthesis. However, the use of organometallics in batch mode on a pilot and industrial scale is challenging for safety reasons and frequently requires expensive cryogenic process conditions. A change to continuous processing in flow mode can provide major advantages for process safety and economics. In this study, we compare static and dynamic flow reactor technologies for two important organolithium (butyllithium and hexyllithium)-enabled transformations: deprotonations and bromine/lithium exchange reactions. Using higher concentrated (≥3 M) butyllithium (BuLi) solutions, i.e., reaction mixtures with reduced hydrocarbon content, decreases the risk of reactor fouling and allows for increased space/time yields. In the flow mode, the observed reactions could be carried out under more convenient conditions, i.e., at higher temperatures compared to the batch mode, and the deprotonation reaction even at ambient temperature instead of -78°C. The formation of precipitates with the risk of clogging can be further reduced by changing from static flow to dynamic spinning disk reactor technol. The SpinPro reactor system from Flowid has been identified to ensure robust performance, as it tolerates salt precipitations and can provide excellent mass transfer conditions. Flow process technol. using concentrated organolithium products can provide unique benefits for the manufacturing of pharmaceutical intermediates, agrochem. products, and specialty chems.

Organic Process Research & Development 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 C20H23N3O2S, Name: 1-Methylpyrazole.

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

Hoeppner, F. D. published the artcileMO calculations on photographic development. IX. Experimental and quantum chemical investigations on the acidity of 5-pyrazolones, Computed Properties of 14580-22-4, the publication is Journal fuer Praktische Chemie (Leipzig) (1976), 318(4), 555-64, database is CAplus.

The pKs values of 49 derivatives of 5-pyrazolone were measured by potentiometric titration and their 1H-NMR spectra were recorded in Me2SO-d6. The exptl. acidity order correlates with both Hammett substitution constants and HMO electron densities.

Journal fuer Praktische Chemie (Leipzig) 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, Computed Properties of 14580-22-4.

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

Nam, Mina published the artcileDiscovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine derivatives as selective metabotropic glutamate receptor 1 antagonists for the potential treatment of neuropathic pain, Application of 3-Isopropyl-1H-pyrazole-5-carboxylic acid, the publication is European Journal of Medicinal Chemistry (2015), 245-258, database is CAplus and MEDLINE.

Metabotropic glutamate receptor 1 (mGluR1) was a prime target for drug discovery due to its heavy involvement in various brain disorders. Recent studies suggested that mGluR1 is associated with chronic pain and can serve as a promising target for the treatment of neuropathic pain. In an effort to develop a novel mGluR1 antagonist, the authors designed and synthesized a library of compounds with tetrahydrothieno[2,3-c]pyridine scaffold. Among these compounds, compound 2-(Benzylamino)-6-(3-methyl-1H-pyrazole-5-carbonyl)4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carbonitrile and 2-(Benzylamino)-6-(4-fluorobenzoyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carbonitrile showed excellent antagonistic activity in vitro and demonstrated pain-suppressing activity in animal models of pain. Both compounds were orally active, and compound 2-(Benzylamino)-6-(3-methyl-1H-pyrazole-5-carbonyl)4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carbonitrile exhibited a favorable pharmacokinetic profile in rats. The authors believe that these compounds can provide a promising lead compound that is suitable for the potential treatment of neuropathic pain.

European Journal of Medicinal Chemistry published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C7H10N2O2, Application of 3-Isopropyl-1H-pyrazole-5-carboxylic acid.

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

Yoon, Suyoung published the artcileStructure-activity relationship of leucyladenylate sulfamate analogues as leucyl-tRNA synthetase (LRS)-targeting inhibitors of Mammalian target of rapamycin complex 1 (mTORC1), Safety of 3-Isopropyl-1H-pyrazole-5-carboxylic acid, the publication is Bioorganic & Medicinal Chemistry (2019), 27(6), 1099-1109, database is CAplus and MEDLINE.

Leucyl-tRNA synthetase (LRS) plays an important role in amino acid-dependent mTORC1 signaling, which is known to be associated with cellular metabolism and proliferation. Therefore, LRS-targeting small mols. that can suppress mTORC1 activation may provide an alternative strategy to current anticancer therapy. In this work, we developed a library of leucyladenylate sulfate analogs by extensively modifying three different pharmacophoric regions comprising adenine, ribose and leucine. Several effective compounds were identified by cell-based mTORC1 activation assays and further tested for anticancer activity. The selected compounds mostly exhibited selective cytotoxicity toward five different cancer cell lines, supporting the hypothesis that the LRS-mediated mTORC1 pathway is a promising alternative target to current therapeutic approaches.

Bioorganic & Medicinal Chemistry published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C3H5BN2O2, Safety of 3-Isopropyl-1H-pyrazole-5-carboxylic acid.

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

Lee, Je-Heon published the artcileDiscovery of substituted indole derivatives as allosteric inhibitors of m⁶A-RNA methyltransferase, METTL3 -14 complex, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Drug Development Research (2022), 83(3), 783-799, database is CAplus and MEDLINE.

In this study, the discovery of the first allosteric inhibitor of the METTL3-14 complex I = [R¹ = H, CH₃; R² = (4-methoxycarbonylphenoxy), (4-carbamoylphenoxy), (4-carboxyphenoxy), etc.] and II [R³ = 4-Cl-Ph, 4-F-phenyl; R⁴ = Ph, benzyl, [4-(3,5-dichlorophenyl)phenyl], etc] was described based on structure-activity relationship (SAR) and optimization studies of the hit compound, 4-[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]-ethoxy]benzoic acid. Compound II [R³ = 4-F-phenyl; R⁴ = [4-(3,5-dichlorophenyl)phenyl]] was optimized throughout the modifications of 4 different regions of the structure, and it displayed potent enzyme inhibitory activity of the METTL3-14 complex (IC₅₀ = 2.81μM) and an antiproliferative effect in the AML cell lines by suppressing the m6A level of mRNA. The inhibition mechanism and binding mode of II [R³ = 4-F-phenyl; R⁴ = [4-(3,5-dichlorophenyl)phenyl]], were based on the interaction of the reversible and noncompetitive inhibitory profile at the allosteric site along with selectivity for the METTL3-14 complex relative to each subunit enzyme or truncated complex enzyme.

Drug Development Research 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, Recommanded Product: 1H-Pyrazole-4-boronic acid.

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

Takeuchi, Craig S. published the artcileDiscovery of a Novel Class of Highly Potent, Selective, ATP-Competitive, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin (mTOR), Quality Control of 763120-58-7, the publication is Journal of Medicinal Chemistry (2013), 56(6), 2218-2234, database is CAplus and MEDLINE.

A series of novel, highly potent, selective, and ATP-competitive mammalian target of rapamycin (mTOR) inhibitors based on a benzoxazepine scaffold have been identified. Lead optimization resulted in the discovery of inhibitors with low nanomolar activity and greater than 1000-fold selectivity over the closely related PI3K kinases. Compound I (XL388) inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. Furthermore, this compound displayed good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. Oral administration of compound I to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity.

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 C17H20ClN3, Quality Control of 763120-58-7.

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