Day: November 21, 2022

Kuhn, Sonja published the artcileActin Assembly around the Shigella-Containing Vacuole Promotes Successful Infection, Application In Synthesis of 71203-35-5, the publication is Cell Reports (2020), 31(6), 107638, database is CAplus and MEDLINE.

The enteroinvasive bacterium Shigella flexneri forces its uptake into non-phagocytic host cells through the translocation of T3SS effectors that subvert the actin cytoskeleton. Here, we report de novo actin polymerization after cellular entry around the bacterium-containing vacuole (BCV) leading to the formation of a dynamic actin cocoon. This cocoon is thicker than any described cellular actin structure and functions as a gatekeeper for the cytosolic access of the pathogen. Host CDC42, TOCA-1, N-WASP, WIP, the Arp2/3 complex, cortactin, coronin, and cofilin are recruited to the actin cocoon. They are subverted by T3SS effectors, such as IpgD, IpgB1, and IcsB. IcsB immobilizes components of the actin polymerization machinery at the BCV dependent on its fatty acyltransferase activity. This represents a unique microbial subversion strategy through localized entrapment of host actin regulators causing massive actin assembly. We propose that the cocoon promotes subsequent invasion steps for successful Shigella infection.

Cell Reports 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 C22H21N3O3S, Application In Synthesis of 71203-35-5.

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

Harris, Philip A. published the artcileDiscovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases, Name: (1H-Pyrazol-5-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2017), 60(4), 1247-1261, database is CAplus and MEDLINE.

RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-mol. inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, the authors report the lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clin. candidate GSK2982772 (compound I), currently in phase 2a clin. studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound I potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochem. and ADMET properties of I, combined with high potency, led to a predicted low oral dose in humans.

Journal of Medicinal Chemistry 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

Hornberger, Keith R. published the artcileDiscovery and optimization of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1, Application of 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(16), 4517-4522, database is CAplus and MEDLINE.

The discovery and potency optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. Micromolar hits taken from high-throughput screening were optimized for biochem. and cellular mechanistic potency to ∼10 nM, as exemplified by compound 12az. Application of structure-based drug design aided by co-crystal structures of TAK1 with inhibitors significantly shortened the number of iterations required for the optimization.

Bioorganic & 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 C3H5BN2O2, Application of 1H-Pyrazole-4-boronic acid.

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

Beyer, Hans published the artcileThiazoles. XXVIII. 2,2′-Dithiazolylamine and its nitration products, Category: pyrazoles-derivatives, the publication is Chemische Berichte (1956), 1602-8, database is CAplus.

cf. C.A. 51, 2813c. 4,4′-Di- and 4,4′,5,5′-tetrasubstituted 2,2′-dithiazolylamines have been prepared Heating 4.5 g. dithiobiuret (I) and 11 g. CH₂ClCHClOEt in 80 cc. 60% EtOH 1 hr. on a water bath, adding 30 cc. 5% HCl, decomposing the precipitated HCl salt with NaOAc, and concentrating the solution to 10 cc. yield 64% 2,2′-dithiazolylamine (II), yellow leaflets, m. 215°, which is also obtained in 75% yield when 6.8 g. I and 7.8 g. CH₂ClCHO is heated 1 hr. on a water bath and the precipitated II.HCl is treated with NaOAc (HCl salt, needles, m. 214°; N-Ac derivative, small rods, m. 121-2°). Heating an intimate mixture of 11.4 g. 2-amino-4-methylthiazole (III) and 15 g. III.HCl 0.5 hr. at 200°, extracting the powd. melt with boiling H₂O, and recrystallizing the residue from 2N HCL give 30% 4,4′-dimethyl-2,2′-dithiazolylamine (IV).HCl, yellow needles, m. 276-8° (decomposition), which, with NaOAc, yields IV, needles, m. 153-4°, also obtained in 70% yield on heating 5.4 g. I with 11.1 g. AcCH₂Cl in 50 cc. EtOH 2 hrs. on a water bath. Heating a mixture of 17.6 g. 2-amino-4-phenylthiazole (V) and 21.5 g. V.HBr 1 hr. at 200°, extracting the powd. melt with hot H₂O and C₆H₆, and recrystallizing the residue from Me₂CO yield 85% 4,4′-diphenyl-2,2′-dithiazolylamine (VI), yellow rhombs, m. 219-21°, also obtained in 93% yield on mixing 2.7 g. I and 8 g. PhCOCH₂Cl, each dissolved in 25 cc. EtOH (N-Ac derivative of VI, needles or leaflets, m. 138°; N-Bz derivative, needles, m. 165-7°). Treating 3.3 g. VI in 150 cc. AcOH with solid NaNO₂ in small portions with cooling gives 72% 4,4′-diphenyl-2,2′-dithiazolylnitrosamine, red-brown cubes, m. 228-9° (decomposition), crystallizing from C₅H₅N with 1 mol. C₅H₅N, red rods, losing its C₅H₅N on heating at 200°. Treating 5.5 g. 2-amino-4,5-dimethylthiazole-HCl with 0.66 g. solid NaOH 15 min. at 220° yields 53% 4,4′,5,5′-tetramethyl-2,2′-dithiazolylamine, rhombs, m. 215-16°, which is also obtained in 78% yield when 1.3 g. I and 2.8 g. AcCHClMe is refluxed 0.5 hr. in 10 cc. MeOH. Fusing 29.3 g. 2-amino-4,5-diphenylthiazole (VII).HCl (or HBr) and 25.7 g. VII 0.5 hr. at 220° and triturating the melt with hot H₂O give 40% (or 70%) 4,4′,5,5′-tetraphenyl-2,2′-dithiazolylamine, rhombic leaflets, m. 208-9°, which is also obtained in 60% yield when 1.3 g. I and 3.2 g. desyl chloride is refluxed 1 hr. in 20 cc. EtOH (Ac derivative, platelets, m. 213-15°). Refluxing 1.7 g. 4-methyl-2-thiazolylthiourea and 2 g. PhCOCH₂Br in 50 cc. EtOH 1 hr. yields 90% 4-methyl-4′-phenyl-2,2′-dithiazolylamine, needles, m. 245°. Heating 2.6 g. I and 9.6 g. m-O₂NC₆H₄COCH₂Br in 100 cc. EtOH 1 hr. on a water bath gives 85% 4,4′-bis(m-nitrophenyl)-2,2′-dithiazolylamine (VIII), yellow needles, m. 252-3° [N-Ac derivative, yellow needles, m. 296-8° (decomposition)]. Heating 4.5 g. I and 9.6 g. CH₂ClCHClOEt in 50 cc. EtOH 1 hr. on a water bath gives 29.2% 2-thiazolylthiourea-HCl, clusters of felted needles, m. 203-4° (decomposition); from the mother liquor 3.5 g. II is isolated. Heating 5.4 g. I and 7.4 g. CH₂ClOMe 1 hr. on a water bath gives a mixture of 4-methyl-2-thiazolylthiourea (IX).HCl and IV.HCl which are separated by fractional crystallization from EtOH. Decomposition of IX.HCl with NaOAc gives IX, small rods, m. 174-5°. Treating 1.8 g. II in 25 cc. concentrated H₂SO₄ at -5° dropwise with 2 cc. concentrated HNO₃ in 10 cc. concentrated H₂SO₄ and, after 2 hrs., pouring the mixture onto ice yield 85% 5,5′-dinitro-4,4′-dimethyl-2,2′-dithiazolylamine, small orange-red rods, decompose 233°; it dissolves in alc. NaOH with a deep red color. Similar nitration of 3.6 g. VI in 150 cc. boiling Me₂CO with 10 cc. concentrated H₂SO₄ and concentrated HNO₃ (1:1) gives 86% 5,5′-dinitro-4,4′-diphenyl-2,2′-thiazolylamine (X), orange-red leaflets, m. 229-31° (decomposition); it crystallizes with 1 mole C₅H₅N, deep red rods. Adding Zn dust in small portions to 4.25 g. X in 25 cc. Ac₂O and 10 cc. AcOH, refluxing the mixture 0.5 hr., pouring the filtered solution into H₂O, and recrystallizing the precipitate from AcOH yield 5,5′-diamino-4,4′-diphenyl-2,2′-dithiazolylamine pentaacetate, rhombs, m. 208-9°. Treating 11.4 g. VIII with 100 cc. concentrated HNO₃ and warming the mixture on a water bath give 2.1 g. O₂NC₆H₄CO₂H, m. 141-2°; similarly, X yields BzOH.

Chemische Berichte published new progress about 23286-70-6. 23286-70-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Ester, name is Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, and the molecular formula is C7H11N3O2, Category: pyrazoles-derivatives.

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

Nitu, Sabina published the artcileAzoic compounds obtained from 1H-5-amino-4-ethoxycarbonyl-3-methyl-pyrazole and phenols or phenolic derivatives, Category: pyrazoles-derivatives, the publication is Revista de Chimie (Bucharest, Romania) (2008), 59(12), 1352-1354, database is CAplus.

The coupling of 1H-4-ethoxycarbonyl-3-methyl-pyrazol-5-yldiazonium chloride with phenols and Ph ethers I (R¹ = H, Me, PhCH₂; R² = 4-Me, 3-MeO, 2,4-F₂, etc.) affords the corresponding arylazopyrazoles II which were characterized by TLC, IR, VIS and NMR spectroscopy. The similar reaction with 4-hydroxybenzoic acid was accompanied by decarboxylation to give (4-hydroxyphenyl)azo derivatives

Revista de Chimie (Bucharest, Romania) published new progress about 23286-70-6. 23286-70-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Ester, name is Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, and the molecular formula is C7H11N3O2, Category: pyrazoles-derivatives.

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

Karlsson, Staffan published the artcileFrom Milligram to Kilogram Manufacture of AZD4573: Making It Possible by Application of Enzyme-, Iridium-, and Palladium-Catalyzed Key Transformations, HPLC of Formula: 2057507-56-7, the publication is Organic Process Research & Development (2022), 26(3), 601-615, database is CAplus.

With the first generation medicinal chem. synthesis as a starting point, herein process development of AZD4573, an oncol. drug candidate was described. In addition to improved yields and removal of chromatog. steps, other factors such as availability of starting materials as well as safety of the chem. involved were addressed. With several steps involving volatile, reactive, and non-UV active materials, reaction optimization was facilitated by implementing off-line ¹H NMR anal. of crude mixtures Key transformations targeted for process development included a Wolff-Kishner reduction, an iridium-catalyzed borylation, and enzymic resolution of a racemic amino-ester.

Organic Process Research & Development published new progress about 2057507-56-7. 2057507-56-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazoles, name is 3-Bromo-5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole, and the molecular formula is C8H11BrN2, HPLC of Formula: 2057507-56-7.

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

Venturella, Pietro published the artcileReactivity of the flavonic ring. I. Action of phenylhydrazine, Computed Properties of 13599-22-9, the publication is Annali di Chimica (Rome, Italy) (1961), 34-44, database is CAplus.

A pyrazoline derivative, C₂₁H₁₈ON₂ was obtained from flavanone (I) by action of NH₂NHPh (II) and its structure was studied by an oxidizing demolition and a direct synthesis. Pure I (0.5 g.) in 5 cc. AcOH was treated with 0.3 g. II to yield after 12 hrs. at room temperature the phenylhydrazone (III), m. 146-7° (EtOH). I (0.5 g.) in 5 cc. AcOH and 0.3 g. II, refluxed 1 hr., the mixture cooled, filtered, and the product crystallized (EtOH) gave 3-(o-hydroxyphenyl)-1,5-diphenylpyrazoline (IV), m. 164-5°. I and II, melted in a test tube, gave IV. 2-Hydroxychalcone (V) (0.5 g.) in 10 cc. AcOH with 0.35 g. II after 2-3 days at room temperature gave IV. V (1 g.) in 15 cc. EtOH refluxed 3 hrs. with 0.6 g. II, cooled, and the product crystallized (EtOH) gave IV. V (0.2 g.) melted with II in excess gave IV. IV (0.5 g.) with 5 cc. Ac₂O and 1 g. AcOMe refluxed 1.5 hrs., poured into H₂O, and the product crystallized gave 3-(o-acetoxyphenyl)-1,5-diphenylpyrazoline (VI), m. 111-12°. 3-(o-Hydroxy-phenyl)-1,5-diphenylpyrazole (VII), m. 105-6°, was prepared from o-hydroxydibenzoylmethane and II. Analogously was prepared 5-(o-hydroxyphenyl)-1,3-diphenylpyrazole (VIII), m. 162-3°. VII (1 g.) in 20 cc. EtOH with metallic Na in excess refluxed 2 hrs. and the product crystallized gave IV. Boiling 1 g. IV in 30 cc. 0.5N NaOH with 7 g. KMnO₄ in 50 cc. H₂O gave 1,5-diphenyl-3-pyrazolecarboxylic acid. Ultraviolet and infrared spectra of IV, VI, VII and VIII were given.

Annali di Chimica (Rome, Italy) published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C18H26ClN3O, Computed Properties of 13599-22-9.

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

Rather, Imran Ibni Gani published the artcileExploration of potential role of Rho GTPase in nicotine dependence-induced withdrawal syndrome in mice, Product Details of C22H21N3O3S, the publication is Environmental Science and Pollution Research (2022), 29(12), 17417-17424, database is CAplus and MEDLINE.

The RhoA gene showed an important genotypic association with nicotine dependence and smoking initiation. The current study aims to investigate the effect of the Rho GTPase inhibitor ML141 in the progression of nicotine dependence in a mice model of precipitated nicotine withdrawal syndrome by mecamylamine. The exptl. procedure involved administration of 2.5 mg/kg nicotine dissolved in normal saline s.c. (s.c) four times a day consecutively for 7 days and last single dose in the morning on 8th day. ML-141 was dissolved in DMSO (DMSO) and was administered daily with nicotine as corrective treatment at a dose of 1,5 and 10 mg/kg (p < 0.05). An injection of 3 mg/kg of mecamylamine i.p. (i.p.) was given an hour later than the last nicotine dose on the day 8 to precipitate withdrawal of nicotine and withdrawal severity was assessed by measuring hyperalgesia, piloerection, jumping frequency, tremors, and withdrawal severity score (WSS). Various behavioral changes such as hyperalgesia, piloerection, jumping frequency, and tremors were monitored and WSS was calculated ML-141 a selective Rho GTPase inhibitor was found to show dose-dependent effect on all these parameters. Inhibition of Rho GTPase was found to reduce the severity of withdrawal syndrome; therefore, it can be concluded that Rho GTPase would serve as a suitable biol. target by regulating the reward system in brain and could be used as new target for drug discovery.

Environmental Science and Pollution Research 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 C22H21N3O3S, Product Details of C22H21N3O3S.

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

Zhao, Pihong published the artcilePlutonium(IV) and (V) Sorption to Goethite at Sub-Femtomolar to Micromolar Concentrations: Redox Transformations and Surface Precipitation, Name: 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, the publication is Environmental Science & Technology (2016), 50(13), 6948-6956, database is CAplus and MEDLINE.

Pu(IV) and Pu(V) sorption to goethite was investigated over a concentration range of 10^-15-10^-5 M at pH 8. Experiments with initial Pu concentrations of 10^-15 – 10^-8 M produced linear Pu sorption isotherms, demonstrating that Pu sorption to goethite is not concentration-dependent across this concentration range. Equivalent Pu(IV) and Pu(V) sorption K_d values obtained at 1 and 2-wk sampling time points indicated that Pu(V) is rapidly reduced to Pu(IV) on the goethite surface. Further, it suggested that Pu surface redox transformations are sufficiently rapid to achieve an equilibrium state within 1 wk, regardless of the initial Pu oxidation state. At initial concentrations >10^-8 M, both Pu oxidation states exhibited deviations from linear sorption behavior and less Pu was adsorbed than at lower concentrations NanoSIMS and HRTEM anal. of samples with initial Pu concentrations of 10^-8 – 10^-6 M indicated that Pu surface and/or bulk precipitation was likely responsible for this deviation. In 10^-6 M Pu(IV) and Pu(V) samples, HRTEM anal. showed the formation of a body centered cubic (bcc) Pu₄O₇ structure on the goethite surface, confirming that reduction of Pu(V) had occurred on the mineral surface and that epitaxial distortion previously observed for Pu(IV) sorption occurs with Pu(V) as well.

Environmental Science & Technology 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 C6H17NO3Si, Name: 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one.

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

Dhankhar, Priyanka published the artcilePhotoluminescent report on red light emitting europium(III) complexes with heterocyclic acid, Category: pyrazoles-derivatives, the publication is Spectroscopy Letters (2020), 53(4), 256-269, database is CAplus.

Five luminescent europium (III) carboxylate complexes have been synthesized by using ligand 3-isopropylpyrazole-5-carboxylic acid as primary ligand and 4,4′-dimethyl-2,2′-bipyridyl, 2,2′-bipyridyl, 5,6-dimethyl-1,10-phenanthroline and 1,10-phenanthroline as secondary ligands and characterized through various techniques. These complexes exhibit excellent thermal stability and characteristic europium centered photoemission spectra under the excitation of UV light. Luminescence decay curves, Judd-Ofelt anal., internal quantum efficiency and energy transfer mechanism have also been discussed. The color coordinates and color purity are calculated to investigate red emission of the complexes. The study results reveal that these complexes can be potentially used as red light emitting materials in various optoelectronic devices.

Spectroscopy Letters 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, Category: pyrazoles-derivatives.

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