Day: December 5, 2022

Megahed, Sarah H. published the artcileNovel 2,4-disubstituted quinazoline analogs as antibacterial agents with improved cytotoxicity profile: Modification of the benzenoid part, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2022), 128531, database is CAplus and MEDLINE.

Bacterial resistance to currently used antibiotics demands the development of novel antibacterial agents with good safety margins and sufficient efficacy against multi-drug resistant isolates. We have previously described the synthesis of N-butyl-2-(butylthio)quinazolin-4-amine (I) as an optimized hit with broad-spectrum antibacterial activity and low cytotoxicity. In addition, we have identified a potential growing vector for this series of compounds Herein, we describe further hit optimization which includes systematic diversifications of both the benzenoid part and the substituents at position 6 and 7 of compound I. Growing of the mol. beside the core modifications yielded several compounds with remarkable anti(myco)bacterial activity against a panel of pathogenic bacteria, including drug-resistant strains. 3-(4-(Butylamino)-2-(butylthio)quinazolin-6-yl)phenol showed a 2-4 fold improvement in activity than I against S. aureus Newman, S. pneumoniae DSM-20566 and E. faecalis DSM-20478. The compounds also showed a good safety profile towards human HepG2 cells.

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

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

Yang, Guang published the artcileCadmium(II) Complexes of 4-(4-Pyridyl)Pyrazole: A Case of Two Conformational Supramolecular Isomers Polythreaded in the Same Crystal and a Rare Example of 5-Connected nov Net, Related Products of pyrazoles-derivatives, the publication is Crystal Growth & Design (2008), 8(3), 981-985, database is CAplus.

Stoichiometric control of the reactions of Cd(BF₄)₂ with 4-(4-pyridyl)pyrazole (4-py-pzH) gave four different crystalline products: mononuclear [Cd(4-py-pzH)₄(H₂O)₂](BF₄)₂ (1), a polythreaded two-dimensional (2D) + 1-dimensional (1D) complex [Cd(NCS)₂(μ-4-py-pzH)₂]_n (2), a 1-dimensional chain {[Cd(NCS)₂(4-Hpy-pzH)₂][Cd(NCS)₄]}_n (3), and a 3-dimensional [Cd(NCS)₂(μ-4-py-pzH)]_n (4). Complex 2 consists of stacked 2-dimensional square layers penetrated by columns of 1-dimensional ribbons. The 2-dimensional and 1-dimensional components of 2 are conformational supramol. isomers [Cd(NCS)₂(μ-4-py-pzH)₂]_n. The topol. underlying 4 represents a rare example of a 5-connected nov net observed in metal-organic frameworks.

Crystal Growth & Design published new progress about 19959-71-8. 19959-71-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Pyridine, name is 4-(1H-Pyrazol-4-yl)pyridine, and the molecular formula is C42H63O3P, Related Products of pyrazoles-derivatives.

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

Lee, Angeline C.-H. published the artcileThieno[3,2-d]pyrimidin-4(3H)-one derivatives as PDK1 inhibitors discovered by fragment-based screening, Computed Properties of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(12), 4023-4027, database is CAplus and MEDLINE.

Ligand efficient fragments binding to PDK1 were identified by an NMR fragment-based screening approach. Computational modeling of the fragments bound to the active site led to the design and synthesis of a series of novel 6,7-disubstituted thienopyrimidin-4-one compounds e. g., I, with low micromolar inhibitory activity against PDK1 in a biochem. enzyme assay.

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, Computed Properties of 763120-58-7.

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

Gummadi, Venkateshwar Rao published the artcileDiscovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode, Related Products of pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(17), 4911-4918, database is CAplus and MEDLINE.

We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7b, 7m and 7n demonstrate excellent potencies in biochem. and cellular assays. X-ray crystal structure of one of the compounds (7k) revealed a unique binding mode with the benzyl group occupying the back pocket, explaining its potency towards ALK and selectivity over tested kinases particularly Aurora-A. This binding mode is in contrast to that of known ALK inhibitors such as Crizotinib and NVP-TAE684 which occupy the ribose binding pocket, close to DFG motif.

Bioorganic & Medicinal Chemistry Letters published new progress about 1415825-05-6. 1415825-05-6 belongs to pyrazoles-derivatives, auxiliary class Boronic acid and ester,Boronic Acids,Boronate Esters, name is 1-(2-Fluorobenzyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, and the molecular formula is C16H20BFN2O2, Related Products of pyrazoles-derivatives.

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

Teske, Kelly A. published the artcileParallel Chemistry Approach to Identify Novel Nuclear Receptor Ligands Based on the GW0742 Scaffold, SDS of cas: 763120-58-7, the publication is ACS Combinatorial Science (2017), 19(10), 646-656, database is CAplus and MEDLINE.

We describe the parallel synthesis of novel analogs of GW0742, a peroxisome proliferator-activated receptor δ (PPARδ) agonist. For that purpose, modified reaction conditions were applied, such as a solid-phase palladium-catalyzed Suzuki coupling. In addition, tetrazole-based compounds were generated as a bioisostere for carboxylic acid-containing ligand GW0742. The new compounds were investigated for their ability to activate PPARδ mediated transcription and their cross-reactivity with the vitamin D receptor (VDR), another member of the nuclear receptor superfamily. We identified many potent PPARδ agonists that were less toxic than GW0742, where ∼65 of the compounds synthesized exhibited partial PPARδ activity (23-98%) with EC₅₀ values ranging from 0.007-18.2 μM. Some ligands, such as compound 32, were more potent inhibitors of VDR-mediated transcription with significantly reduced PPARδ activity than GW0742, however, none of the ligands were completely selective for VDR inhibition over PPARδ activation of transcription.

ACS Combinatorial Science 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 C2H4ClNO, SDS of cas: 763120-58-7.

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

Reiberger, Robert published the artcileSynthesis and In Vitro Evaluation of C-7 and C-8 Luteolin Derivatives as Influenza Endonuclease Inhibitors, Synthetic Route of 724710-02-5, the publication is International Journal of Molecular Sciences (2021), 22(14), 7735, database is CAplus and MEDLINE.

The part of the influenza polymerase PA subunit featuring endonuclease activity is a target for anti-influenza therapies, including the FDA-approved drug Xofluza. A general feature of endonuclease inhibitors is their ability to chelate Mg²⁺ or Mn²⁺ ions located in the enzyme′s catalytic site. Previously, we screened a panel of flavonoids for PA inhibition and found luteolin and its C-glucoside orientin to be potent inhibitors. Through structural anal., we identified the presence of a 3′,4′-dihydroxyphenyl moiety as a crucial feature for sub-micromolar inhibitory activity. Here, we report results from a subsequent investigation exploring structural changes at the C-7 and C-8 positions of luteolin. Exptl. IC₅₀ values were determined by AlphaScreen technol. The most potent inhibitors were C-8 derivatives with inhibitory potencies comparable to that of luteolin. Bio-isosteric replacement of the C-7 hydroxyl moiety of luteolin led to a series of compounds with one-order-of-magnitude-lower inhibitory potencies. Using X-ray crystallog., we solved structures of the wild-type PA-N-terminal domain and its I38T mutant in complex with orientin at 1.9 Å and 2.2 Å resolution, resp.

International Journal of Molecular Sciences 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, Synthetic Route of 724710-02-5.

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

Mistico, Laetitia published the artcileAccess to Silylated Pyrazole Derivatives by Palladium-Catalyzed C-H Activation of a TMS group, Name: 1-Methylpyrazole, the publication is Chemistry – A European Journal (2016), 22(28), 9687-9692, database is CAplus and MEDLINE.

A simple and efficient approach to new silylated heterocycles of potential interest in medicinal chem. is presented. A set of bromophenyl trimethylsilyl pyrazole intermediates can be transformed by direct organometallic routes into two families of regioisomeric iodoaryl substrates; using either arylzinc or aryllithium chem., the TMS group remains on the pyrazole ring or translocates to the aryl moiety. These two families can then be efficiently transformed into benzo silino pyrazoles thanks to a single-step cyclization relying on the Pd-catalyzed activation of a nonactivated C(sp³)-H bond alpha to a Si atom. The exptl. conditions used, which are fully compatible with the pyrazole ring, suggest that this reaction evolves through a concerted metalation-deprotonation (CMD) mechanism.

Chemistry – A European Journal 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, Name: 1-Methylpyrazole.

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

Kamani, Ronak D. published the artcileOne-Pot Catalyst-Free Direct Sulfenylation of 1-Aryl Pyrazolones with Aryl Thiols at Room Temperature, Product Details of C10H9ClN2O, the publication is ChemistrySelect (2017), 2(30), 9670-9673, database is CAplus.

A novel strategy for N-chlorosuccinimide mediated direct sulfenylation of 1-aryl pyrazolones using aryl thiols was developed at room temperature The protocol was found to be simple, efficient and transition metal-free to afforded the phenyl-pyrazolols I [R = H, Me, OMe, Cl, Br; R¹ = Me, CF₃; R² = H, 4-Me, 2-Cl, 3-Cl, 3,4-(Cl)₂] in good to excellent yields without further purification The prepared compounds I were characterized by ¹H NMR, ¹³C NMR and IR spectroscopy. The skeleton of one of the synthesized compounds I [R = Me; R¹ = Me; R² = 2-Cl] was confirmed by X-ray single crystal diffraction anal. as well as ORTEP diagram.

ChemistrySelect 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, Product Details of C10H9ClN2O.

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

Taavitsainen, Paivi published the artcileMetabolism and mass balance of the novel nonsteroidal androgen receptor inhibitor darolutamide in humans, Computed Properties of 1297537-37-1, the publication is Drug Metabolism & Disposition (2021), 49(6), 420-433, database is CAplus and MEDLINE.

The biotransformation and excretion of darolutamide were investigated in a phase I study. Six healthy male volunteers received a single dose of 300 mg ¹⁴C-darolutamide as an oral solution in the fasted state. Plasma, urine, and feces samples were analyzed for mass balance evaluation by liquid scintillation counting (LSC). Metabolite profiling and identification were determined using liquid chromatog. mass-spectrometry with off-line radioactivity detection using LSC. Complete mass balance was achieved, with mean radioactivity recovery of 95.9% within 168 h (63.4% in urine, 32.4% in feces). The administered 1:1 ratio of (S,R)- and (S,S)-darolutamide changed to approx. 1:5, resp., in plasma. Darolutamide and the oxidation product, keto-darolutamide, were the only components quantifiable by LSC in plasma, accounting for 87.4% of total radioactivity, with a 2.1-fold higher plasma exposure for keto-darolutamide. Aside from darolutamide, the most prominent metabolites in urine were O-glucoronide (M-7a/b) and N-glucuronide (M-15a/b), as well as pyrazole sulfates (M-29, M-24) and glucuronides (M-21, M-22) resulting from oxidative cleavage of the parent. The darolutamide diastereomers were mainly detected in feces. In vitro assays showed that darolutamide metabolism involves a complex interplay between oxidation and reduction, as well as glucuronidation. Interconversion of the diastereomers involves oxidation to keto-darolutamide, primarily mediated by CYP3A4, followed by reduction predominantly catalyzed by cytosolic reductase(s), with aldo-keto reductase 1C3 playing the major role. The latter reaction showed stereoselectivity with preferential formation of (S,S)-darolutamide.

Drug Metabolism & Disposition published new progress about 1297537-37-1. 1297537-37-1 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Chloride,Nitrile,Benzene, name is 2-Chloro-4-(1H-pyrazol-5-yl)benzonitrile, and the molecular formula is C17H20ClN3, Computed Properties of 1297537-37-1.

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

Mohapatra, Purusottam published the artcileCombination therapy targeting the elevated interleukin-6 level reduces invasive migration of BRAF inhibitor-resistant melanoma cells, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Molecular Oncology (2019), 13(2), 480-494, database is CAplus and MEDLINE.

The identification of novel antimetastatic therapeutic targets is necessary for improved treatment of patients with acquired BRAF inhibitor-resistant (BRAFi-R) melanoma, in whom metastasis is a major concern. Our present study focused on the identification of such targets to explore novel antimetastatic therapeutic options for BRAFi-R melanoma patients. We confirmed the development of BRAFi resistance in our BRAFi-treated melanoma cell lines by demonstrating reduced sensitivity to BRAF inhibitors, increased ERK1/2 activity and increased WNT5A expression. Here, we demonstrated for the first time that high secretion of interleukin-6 (IL-6) was associated with increased invasive migration of BRAFi-R melanoma cells. This finding could be readily explained by the increased expression of WNT5A in BRAFi-R melanoma cells and the presence of an IL-6/WNT5A pos. feedback loop in parental melanoma cells. Surprisingly, however, we found that the IL-6/WNT5A pos. feedback loop present in parental melanoma cells was lost during the development of acquired BRAFi resistance, meaning that IL-6 and WNT5A signalling were independent events in BRAFi-R melanoma cells. Despite the absence of an IL-6/WNT5A loop, we found that both an IL-6 blocking antibody and the WNT5A antagonist Box5 alone impaired the elevated invasive migration of BRAFi-R melanoma cells, but combined use of the two was more effective. This impaired invasive migration of BRAFi-R melanoma cells correlated well with the reduction in Cdc42-GTPase activity and alterations of the actin cytoskeleton in these cells. In summary, our novel identification of IL-6 as a key independent promoter of the invasive migration of BRAFi-R melanoma cells stresses that a combination of a blocking IL-6 antibody and administration of the WNT5A antagonist Box5 might be an attractive antimetastatic approach for future treatment of BRAFi-R melanoma patients.

Molecular Oncology 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, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

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