Day: November 21, 2022

Li, Zhaosha published the artcileEffects of pyrazole partial agonists on HCA₂-mediated flushing and VLDL-triglyceride levels in mice, Formula: C7H10N2O2, the publication is British Journal of Pharmacology (2012), 167(4), 818-825, database is CAplus and MEDLINE.

Background and Purpose Niacin can effectively treat dyslipidemic disorders. However, its clin. use is limited due to the cutaneous flushing mediated by the nicotinic acid receptor HCA₂. In the current study, we evaluated two partial agonists for HCA₂, LUF6281 and LUF6283, with respect to their anti-dyslipidemic potential and cutaneous flushing effect. Exptl. Approach In vitro potency and efficacy studies with niacin and the two HCA₂ partial agonists were performed using HEK293T cells stably expressing human HCA₂. Normolipidemic C57BL/6 mice received either niacin or the HCA₂ partial agonists (400 mg·kg^-1·day^-1) once a day for 4 wk for evaluation of their effects in vivo. Key Results Radioligand competitive binding assay showed K_i values for LUF6281 and LUF6283 of 3 and 0.55 μM. [³⁵S]-GTPγS binding revealed the rank order of their potency as niacin > LUF6283 > LUF6281. All three compounds reduced plasma VLDL-triglyceride concentrations similarly, while LUF6281 and LUF6283, in contrast to niacin, did not also exhibit the unwanted flushing side effect in C57BL/6 mice. Niacin reduced the expression of lipolytic genes HSL and ATGL in adipose tissue by 50%, whereas LUF6281 and LUF6283 unexpectedly did not. In contrast, the decrease in VLDL-triglyceride concentration induced by LUF6281 and LUF6283 was associated with a parallel >40% reduced expression of APOB within the liver. Conclusions and Implications The current study identifies LUF6281 and LUF6283, two HCA₂ partial agonists of the pyrazole class, as promising drug candidates to achieve the beneficial lipid lowering effect of niacin without producing the unwanted flushing side effect.

British Journal of Pharmacology 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, Formula: C7H10N2O2.

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

Barraclough, Paul published the artcileInotropic polyazapentalene sulmazole analogs, COA of Formula: C5H7N3O, the publication is Archiv der Pharmazie (Weinheim, Germany) (1992), 325(4), 225-34, database is CAplus and MEDLINE.

Aryl substituted 1H-imidazo[1,2-a]imidazole I, imidazo[2,1-b]thiazole II (X = S), 1,4-dihydroimidazo[4,5-d]imidazole III, and 1(2),4-dihydroimidazo[4,5-c]pyrazoles IV (Y = SOMe, SMe, cyano, CONH₂) and V (Z = cyano, CONH₂) have been prepared Thus, 2-aminoimidazole reacted with 2-bromo-2′,4′-dimethoxyacetophenone to give II (X = NCH₂R¹, R¹ = 2′,4′-dimethoxybenzoyl) which was treated with Zn in aqueous HOAc to give I in 70% yield. An x-ray crystallog. study confirmed the structure of I and showed this analog to exist as the 1H-tautomer. These heterocycles were evaluated as inotropic agents and analogs IV (Y = SOMe, CONH₂) and V (Z = CONH₂) displayed inotropic properties which were less potent in vitro, but more potent in vivo, than those of sulmazole. Structure-activity relationships are discussed.

Archiv der Pharmazie (Weinheim, Germany) published new progress about 3553-12-6. 3553-12-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Amide, name is 3-Acetamidopyrazole, and the molecular formula is C5H7N3O, COA of Formula: C5H7N3O.

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

Large, Jonathan M. published the artcilePotent inhibitors of malarial P. Falciparum protein kinase G: Improving the cell activity of a series of imidazopyridines, Synthetic Route of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2019), 29(3), 509-514, database is CAplus and MEDLINE.

Development of a class of bicyclic inhibitors of the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG), starting from known compounds with activity against a related parasite PKG orthologue, is reported. Examination of key sub-structural elements led to new compounds with good levels of inhibitory activity against the recombinant kinase and in vitro activity against the parasite. Key examples were shown to possess encouraging in vitro ADME properties, and computational anal. provided valuable insight into the origins of the observed activity profiles.

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, Synthetic Route of 763120-58-7.

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

Li, Zheng published the artcileSelective removal of magnesium from lithium-rich brine for lithium purification by synergic solvent extraction using β-diketones and Cyanex 923, Computed Properties of 4551-69-3, the publication is AIChE Journal (2020), 66(7), e16246, database is CAplus and MEDLINE.

In the production of battery-grade and high-purity Li₂CO₃, it is essential to remove magnesium impurities. The state-of-the-art solvent extraction (SX) process using Versatic Acid 10 and D2EHPA co-extracts 3.3-5.5% lithium, while removing 86-98% magnesium. Here, we demonstrate that synergic SX systems containing a β-diketone (HPMBP, HTTA or HDBM) and Cyanex 923 are highly selective for magnesium extraction over lithium (separation factor α > 1000). The extracted magnesium and lithium complexes have the stoichiometry of [Mg·A₂·(C923)₂] and [Li·A_x·(C923)₂] (x = 1, 2), resp. (A represents deprotonated β-diketone). The three β-diketone synergic SX systems all considerably outperformed the Versatic Acid 10 system for magnesium removal from a synthetic solution containing 24 g L^-1 Li and 0.24 g L^-1 Mg. In a three-stage batch counter-current extraction, the HPMBP and Cyanex 923 synergic SX system removed 100% magnesium with only 0.6% co-extraction of lithium. This excellent Mg/Li separation is the best result reported so far.

AIChE Journal 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, Computed Properties of 4551-69-3.

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

Bebbington, David published the artcileThe discovery of the potent aurora inhibitor MK-0457 (VX-680), HPLC of Formula: 851435-28-4, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(13), 3586-3592, database is CAplus and MEDLINE.

The identification of a novel series of Aurora kinase inhibitors and exploitation of their SAR is described. Replacement of the initial quinazoline core with a pyrimidine scaffold and modification of substituents led to a series of very potent inhibitors of cellular proliferation. MK-0457 (I) has been assessed in Phase II clin. trials in patients with treatment-refractory chronic myelogenous leukemia (CML) or Philadelphia chromosome-pos. acute lymphoblastic leukemia (Ph + ALL) containing the T315I mutation.

Bioorganic & Medicinal Chemistry Letters published new progress about 851435-28-4. 851435-28-4 belongs to pyrazoles-derivatives, auxiliary class Imidazole,Pyrimidine,Chloride,Amine, name is 2-Chloro-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine, and the molecular formula is C9H10ClN5, HPLC of Formula: 851435-28-4.

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

Chen, Pei published the artcileDiscovery of 6,7-dihydro-5H-pyrrolo[3,4-d] pyrimidine derivatives as a new class of ATR inhibitors, HPLC of Formula: 724710-02-5, the publication is Bioorganic & Medicinal Chemistry Letters (2022), 128651, database is CAplus and MEDLINE.

Ataxia telangiectasia and Rad3-related (ATR) kinase is a key regulating protein within the DNA damage response (DDR), responsible for sensing replication stress (RS), and has been considered as a potential target for cancer therapy. Herein, we report the discovery of a series of 6,7-dihydro-5H-pyrrolo[3,4-d]-pyrimidine derivatives as a new class of ATR inhibitors. Among them, compound 5g exhibits an IC50 value of 0.007 μM against ATR kinase. In vitro, 5g displays good anti-tumor activity and could significantly reduce the phosphorylation level of ATR and its downstream signaling protein. Overall, this study provides a promising lead compound for subsequent drug discovery targeting ATR kinase.

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, HPLC of Formula: 724710-02-5.

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

Wilde, Richard G. published the artcileACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes, Recommanded Product: 4-Bromo-1-methyl-1H-pyrazol-5-amine, the publication is Bioorganic & Medicinal Chemistry (1996), 4(9), 1493-1513, database is CAplus and MEDLINE.

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. The most active compounds were thiopyrans I [R¹ = pentyl, octyl]. Minor changes in structure had a significant effect in optimization of the biol. activity of this series of compounds

Bioorganic & Medicinal Chemistry published new progress about 105675-85-2. 105675-85-2 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Bromide,Amine, name is 4-Bromo-1-methyl-1H-pyrazol-5-amine, and the molecular formula is C10H9ClN2O, Recommanded Product: 4-Bromo-1-methyl-1H-pyrazol-5-amine.

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

Atanassova, Maria published the artcileDetermination of pK_aIL Values of Three Chelating Extractants in ILs: Consequences for the Extraction of 4f Elements, Product Details of C17H14N2O2, the publication is Journal of Solution Chemistry (2015), 44(3-4), 606-620, database is CAplus.

Aqueous-ionic liquid biphasic systems have been examined in terms of water and acid solubilities in the IL-rich phase at ambient temperature The biphasic mixtures were comprised of acids of various concentrations (H⁺; Cl^–, H⁺; NO^–₃, H⁺; ClO^–₄, mainly from 1 × 10^-2 to 1 × 10^-4 mol·dm^-3) and four ionic liquids of the imidazolium family [C₁C_ni.m.][Tf₂N] (n = 4, 6, 8 and 10). The effects of ionic medium (μ = 0.1 mol·dm^-3, by use of Na⁺; Cl^–, Na⁺; NO^–₃ or Na⁺; ClO^–₄, according to the acid investigated), the nature of the IL cation as well as the nature of the acid on the mutual solubilities of (H₂O, H⁺, [C₁C_ni.m.]⁺ and [Tf₂N]^–) entities were determined Then, three chelating compounds (HL), which belong to the β-diketone family (thenoyltrifluoroacetone (HTTA), 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one (HP) and 4-benzoyl-3-phenyl-5-isoxazolone (HPBI)), were added to [C₁C₄i.m.][Tf₂N] and subsequent determination of the H⁺ distribution between the two phases allowed the determination of their dissociation constants (pK_aIL) in the water-saturated ionic liquid phase. A very strong effect of the IL cation on the HTTA pK_aIL value was observed from n = 4 to n = 10. The influence of this phenomenon on the lanthanide extraction process is discussed.

Journal of Solution Chemistry 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, Product Details of C17H14N2O2.

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

Fusco, Raffaello published the artcileEnamines. V. Synthesis of 1-arylpyrazoles, Recommanded Product: 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, the publication is Gazzetta Chimica Italiana (1961), 1233-49, database is CAplus.

cf. CA 56, 14018c. Enamines and halogenated hydrazones reacted to give pyrazole derivatives In anhyd, conditions 16.7 g. 1-morpholinocyclohex-l-ene (I), 10.1 g. NEt₃, 150 mL. CHCl₃, and 22.6 g. PhNHN: CClCO₂Et added in 50 mL. CHCl₃ was stirred and heated to 40° for 1 h. and kept overnight to give 65% 1-phenyl-3-carbethoxy-4,5,6,7-tetrahydroindazole (II) m. 103-4.5° (EtOH), hydrolyzed by alc. NaOH to 1-phenyl-4,5,6,7-tetrahydroindazole-3-carboxylic acid, m. 164° (AcOH). Similarly, the p-chlorophenyl compound, m. 139-40°, and its corresponding acid m. 218°. Treatment of I with PhNHN:CClAe gave 1-phenyl-3-acetyl-4,5,6,7-tetrahydroindazole, m. 95-6°; phenylhydrazone m. 216° (dilute AcOH). 1-Morpholino-4-methylcyclohex-1-ene gave the 5-Me deriv, of II, m. 129°, hydrolyzed to the corresponding acid m. 198°. 1-Phenyl-3-carbethoxy-4,5,6,7-tetrahydrocydohepta[c]pyrazole (III), m. 87% was prepared from 1-morpholinocyclohept-1-ene and was hydrolyzed to the corresponding acid, m. 166-8°. The 1-(p-chlorophenyl) compd, corresponding to III could not be isolated and was hydrolyzed to the acid, m. 206-7°. From 2 morpholino-3,4-dihydronaphthalene and PhNHN: CClCO₂Et, 1-phenyl-3-carbethoxy-8,9-dihydronaphtho[1,2-c]pyrazole, m. 154-5°, was prepared, giving the acid, m. 170°, on hydrolysis: when decarboxylated at 240°, this gave 1-phenyl-8,9-dihydronaphtho[1,2-c]pyrazole, m. 118°. The compound formed from 1-morpholinocyclopent-1-ene and PhNHN:-CClCO₂Et was an intermediate, C₁₉H₂₅N₃O₃, m. 130° (ale.), converted into the expected 1-phenvl-3-carbethoxy-4,5-dihydrocyclopenta[c] pyrazole, m. 143°. on boiling with AcOH followed by precipitation by addition of water. The corresponding acid, m. 211°; Me ester m. 139°. Similarly the 1-(p-chlorophenyl) compd, gave an adduet, C₁₉H₂₄ClN₃O₃, m. 114° cyclized to the pyrazole, m. 120-1°, which in turn was hydrolyzed to the corresponding free acid, m. 215-16°. Similarly were prepared 1-phenyl-3-carbethoxyindeno[1,2-c]-pyrazole, m. 162-3° (the acid m. 256°), 1-phenyl-3-carbethoxy-4-ethylpyrazole, m. 70° (free acid m. 138°), 1-phenyl-3-carbethoxy-4-n-amylpyrazole, m. 45-6° (free acid m. 121°), [the corresponding 1-(p-chlorophenyl) compd, m. 62° (free acid m. 115°)]. From 2-N-methyl-N-phenyl-amino-4-methylpent-l-ene, the ester prepd, was an oil, b₂ 186°, which gave 1-phenyl-5-isobutylpyrazole-3-carboxylic acid, m. 129°, on hydrolysis, α-(N-Methyl-N-phenyl)-aminostyrene and PhNHN:CClCO₂Et after reaction, evapn, of solvent, steam distn, to remove PhAe, and hydrolysis gave 1,5-diphenylpyrazole-3-carboxylic acid, m. 183°. 1-Phenyl-3-carbethoxy-4-γ-methylaminoethyl-5-methylpyrazole oxalate, m. 174-5° (iso-PrOH), was prepared from 1,2-dimethyl-4,5-dihydropyrrole and gave the corresponding base, as a straw-colored oil, b_1.5 220-40°, which on hydrolysis with 40% HBr gave the free carboxylic acid of the base after addition of Ag₂O to precipitate AgBr, filtration, and passage of H₂S to decomp, the Ag salt; the filtrate evaporated to dryness and the solid washed with MeOH and recrystallized from water gave the acid, m. 297°. 1-Phenyl-3-carbethoxy-4-γ-methylaminopropyl-5-methylpyrazole-HCl, m. 186-7° (iso-PrOH), 1-phenyl-4-γ-methylaminopropyl-5-methylpyrazolecarboxylic acid, m. 270-1° (5% aqueous EtCO-Me), and 1-phenyl-3-acetyl-4-γ-methylaminopropyl-5-methylpyrazole oxalate, m. 17,5-6°, were also prepared

Gazzetta Chimica Italiana 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 C16H12N2O2, Recommanded Product: 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid.

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

Hosseini, Simin S. published the artcileSynthesis, carbohydrate- and DNA-binding studies of cationic 2,2′:6′,2”-terpyridineplatinum(II) complexes containing N- and S-donor boronic acid ligands, HPLC of Formula: 763120-58-7, the publication is Dalton Transactions (2011), 40(2), 506-513, database is CAplus and MEDLINE.

Platinum(II) complexes [Pt(trpy)L](NO₃)_n (L = 3- or 4-pyridineboronic acid (3- or 4-pyB, resp.), n = 2; HL = 4-mercaptophenylboronic acid (HmpB), n = 1; trpy = 2,2′:6′,2”-terpyridine) and [{Pt(trpy)}₂(μ-pzB)](NO₃)₃ (HpzB = 4-pyrazoleboronic acid) were synthesized and fully characterized by multinuclear (¹H, ¹³C, ¹¹B, and ¹⁹⁵Pt) 1-dimensional- and 2-dimensional-NMR spectroscopy and elemental anal. The triflate derivatives [Pt(trpy)(4-pyB)](OTf)₂ and [{Pt(trpy)}₂(μ-pzB)](OTf)₃ were also prepared, and their mol. structures were confirmed by x-ray crystallog. Variable pH ¹H NMR spectroscopy showed that hydroxylation of the boronic acid group occurs in aqueous solution at pH > 5 and the pK_a values for the complexes were determined In buffered aqueous solution (pH 7.4), the complexes bind strongly to simple diols such as catechol and monosaccharides including D-fructose, D-ribose, D-sorbitol and D-mannitol, as determined by isothermal titration calorimetry (ITC). The equilibrium binding constants for these reactions were determined and were found to exceed those of organic boronic acids such as phenylboronic acid by an order of magnitude or greater, an effect that can be directly attributed to the cationic charge of the complexes. Two-dimensional-NMR methods (HSQC and HMBC) were used to elucidate the structures of the carbohydrate adducts [Pt(trpy)(3-pyB)]·D-fructose·NO₃ and [Pt(trpy)(4-pyB)]·D-fructose·NO₃ in aqueous solution DNA-binding experiments with calf-thymus DNA (CT-DNA) indicate an avid DNA-binding interaction by the mononuclear complexes, as determined using thermal melting methods and ITC, but the behavior of dinuclear [{Pt(trpy)}₂(μ-pzB)](NO₃)₃ is complicated and could not be modeled adequately; higher ionic strength solutions and lower temperatures resulted in a similar DNA binding interaction to the mononuclear complexes. The presence of excess D-fructose did not significantly affect the binding of the platinum(II)-trpy complexes to CT-DNA.

Dalton Transactions 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, HPLC of Formula: 763120-58-7.

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