763120-58-7 | pyrazoles-derivatives

Chen, Dizhong’s team published research in Journal of Medicinal Chemistry in 61 | CAS: 763120-58-7

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, Safety of 1H-Pyrazole-4-boronic acid.

Chen, Dizhong published the artcileDesign, Synthesis, and Preclinical Evaluation of Fused Pyrimidine-Based Hydroxamates for the Treatment of Hepatocellular Carcinoma, Safety of 1H-Pyrazole-4-boronic acid, the publication is Journal of Medicinal Chemistry (2018), 61(4), 1552-1575, database is CAplus and MEDLINE.

Class I histone deacetylases (HDACs) are highly expressed and/or upregulated in hepatocellular carcinoma (HCC) and are associated with aggressiveness, spread, and increased mortality of HCC. Activation of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was involved in the development of HCC and acquired resistance to sorafenib. A series of purine or 5H-pyrrolo[3,2-d]pyrimidine based hydroxamates were designed and developed as multitarget drugs to modulate both HDACs and the PI3K/Akt/mTOR pathway. Among 39 cell lines screened, the mols. (e.g., I, II, and III) were the most selective against leukemia, lymphoma, and HCC cells; they also demonstrated target modulation in cancer cell lines and in mice bearing MV4-11 and HepG2 tumors. Compound II in particular showed significant single agent oral efficacy in hypervascular liver cancer models (e.g., HepG2, HuH-7, and Hep3B) and was well-tolerated. These encouraging results, along with its favorable target profile and tissue distribution, warrant further development of II.

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

Yang, Feng V.’s team published research in Bioorganic & Medicinal Chemistry Letters in 20 | CAS: 763120-58-7

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 C7H8N2, HPLC of Formula: 763120-58-7.

Yang, Feng V. published the artcileParallel synthesis of N-biaryl quinolone carboxylic acids as selective M₁ positive allosteric modulators, HPLC of Formula: 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(2), 531-536, database is CAplus and MEDLINE.

An iterative analog library synthesis approach was employed in the exploration of a quinolone carboxylic acid series of selective M₁ pos. allosteric modulators, and strategies for improving potency and plasma free fraction were identified.

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

Wang, Jing’s team published research in Bioorganic & Medicinal Chemistry Letters in 25 | CAS: 763120-58-7

Wang, Jing published the artcileMichael acceptor in gambogic acid-Its role and application for potent antitumor agents, Safety of 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2015), 25(14), 2844-2848, database is CAplus and MEDLINE.

Gambogic acid (GA), a natural product with unique structure, was reported to have broad antiproliferation activities against cancer cell lines. As a reactive Michael acceptor, the 10-position of GA is susceptible to nucleophiles, thus limiting its clin. application as an anticancer agent. Moreover, the 6-OH forms an intramol. hydrogen bond with 8-C=O, which can make the 9, 10 double bond more reactive to nucleophiles. In this essay, two strategies (A and B) were applied to solve the above-mentioned problems. Strategy A was to increase the steric hindrance of C-10 to reduce the activity of GA towards nucleophiles. Strategy B was to replace the hydroxyl of C-6 with other substituents based on the assumption that the intra-mol. hydrogen bond could increase the electrophilicity of C-10. Results showed the electrophilicity of C-10 disappeared as well as the antiproliferation activity against cancer cell lines by introducing a Me group at C-10. Strategy B showed that the electrophilicity of C-10 was reduced dramatically while maintained the activity by replacement of the hydroxyl of C-6 with neutral or basic groups.

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

Garai, Sumanta’s team published research in Bioorganic & Medicinal Chemistry in 50 | CAS: 763120-58-7

Bioorganic & 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, Synthetic Route of 763120-58-7.

Garai, Sumanta published the artcileDesign, synthesis, and pharmacological profiling of cannabinoid 1 receptor allosteric modulators: Preclinical efficacy of C2-group GAT211 congeners for reducing intraocular pressure, Synthetic Route of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry (2021), 116421, database is CAplus and MEDLINE.

Allosteric modulators of cannabinoid 1 receptor (CB1R) show translational promise over orthosteric ligands due to their potential to elicit therapeutic benefit without cannabimimetic side effects. The prototypic 2-phenylindole CB1R allosteric modulator, GAT211 (1), demonstrates preclin. efficacy in various disease models. The limited systematic structure-activity relationship (SAR) data at the C2 position of the indole ring within GAT211 invites the opportunity for further modifications to improve GAT211′s pharmacol. profile while serving to amplify and variegate this library of therapeutically attractive agents. These considerations prompted this focused SAR study in which we substituted the GAT211 C2-Ph ring with heteroaromatic substituents. The synthesized GAT211 analogs were then evaluated in vitro as CB1R allosteric modulators in cAMP and β-arrestin2 assays with CP55,940 as the orthosteric ligand. Furan and thiophene rings (15c-f and 15m) were the best-tolerated substituents at the C2 position of GAT211 for engagement with human CB1R (hCB1R). The SAR around the novel ligands reported allowed direct exptl. characterization of the interaction profile of that pharmacophore with its binding domain in functional, human CB1R, thus offering guidance for accessing subsequent-generation hCB1R allosteric modulators as potential therapeutics. The most potent analog, 15d, markedly promoted orthosteric ligand binding to hCB1R. Pharmacol. profiling in the GTPγS and mouse vas deferens assays demonstrated that 15d behaves as a CB1R agonist-pos. allosteric modulator (ago-PAM), as confirmed electrophysiol. in autoptic neurons. In vivo, 15d was efficacious as a topical agent that significantly reduced intraocular pressure (IOP) in the ocular normotensive murine model of glaucoma. Since elevated IOP is a decisive risk factor for glaucoma and attendant vision loss, our data support the proposition that the 2-phenylindole class of CB1R ago-PAMs has therapeutic potential for glaucoma and other diseases where potentiation of CB1R signaling may be therapeutic.

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

Megahed, Sarah H.’s team published research in Bioorganic & Medicinal Chemistry Letters in 59 | CAS: 763120-58-7

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.

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

Lee, Angeline C.-H.’s team published research in Bioorganic & Medicinal Chemistry Letters in 22 | CAS: 763120-58-7

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.

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

Parmar, Deepa R.’s team published research in ChemistrySelect in 5 | CAS: 763120-58-7

ChemistrySelect 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.

Parmar, Deepa R. published the artcileDesign, Synthesis, In Silico Studies and In Vitro Anticancer Activity of 3-(4-Methoxyphenyl)azetidine Derivatives, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is ChemistrySelect (2020), 5(45), 14296-14302, database is CAplus.

A series of 3-(4-methoxyphenyl)azetidine analogs I [Ar = Ph, 4-MeC₆H₄, 4-FC₆H₄, etc.] were synthesized and screened for their in vitro anticancer activity against nine different human cancer cell lines using the cell counting kit-8 (CCK-8) assay. The toxicity, bioavailability and lipophilicity of all the synthesized compounds I were predicted by using osiris and molinspiration model. Mol. docking study revealed that, compound I [Ar = 2-aminopyridin-4-yl, 2-methoxypyridin-4-yl] were found to be potential inhibitor of human topoisomerase IIα. The cell viability studies exhibited promising antiproliferative activities of the compound I [Ar = 2-aminopyridin-4-yl] (EC₅₀ 0.03μM) was found to be more potent than standard Doxorubicin (EC₅₀ 0.07μM) in U251 cancer cell lines. Similarly, compound I [Ar = 2-methoxypyridin-4-yl] showed considerable potency against four different cancer cell lines (HepG2, U251, A431, 786-O) with EC₅₀ values ranging from 0.46 to 2.13μM.

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

Sudheer Reddy, V.’s team published research in Russian Journal of Bioorganic Chemistry in 48 | CAS: 763120-58-7

Russian Journal of Bioorganic 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 C8H5F3O3, Application In Synthesis of 763120-58-7.

Sudheer Reddy, V. published the artcileSynthesis of Some New N-Substituted Imidazole Derivatives and Their In Vitro Antibacterial Investigation, Application In Synthesis of 763120-58-7, the publication is Russian Journal of Bioorganic Chemistry (2022), 48(3), 643-650, database is CAplus.

Here the synthesis of N-substituted imidazole derivatives I (X = 3-MeOC₆H₄, 4-O₂NC₆H₄, 3,5-F₂C₆H₃, etc.) based on Suzuki coupling reaction of I (X = Br) with various arylboronic acids using Pd(dppf)Cl₂·CH₂Cl₂ as the catalyst and K₂CO₃ as a base in 1,4-dioxane/H₂O (2 : 1) is described. The products were screened for their antibacterial activity against gram-pos. bacterial strains, Bacillus subtilis and Staphylococcus aureus, where the compounds I (X = 4-pyridinyl, 3-F-4-MeOC₆H₃, 3-NCC₆H₄, 3-FC₆H₄, 4-F-3-MeC₆H₃, 4-pyrazolyl) exhibited remarkable activity compared to the reference streptomycin.

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

Grimstrup, Marie’s team published research in Bioorganic & Medicinal Chemistry Letters in 20 | CAS: 763120-58-7

Grimstrup, Marie published the artcileNovel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2, Quality Control of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(3), 1181-1185, database is CAplus and MEDLINE.

Structure-activity relationships have been established by exploring the eastern and western side of 5-thiazolyleacetic acids as CRTH2 (chemoattractant receptor-homologous mol. expressed on Th2 cells) antagonists. Benzhydryl motifs in the 2-position of the thiazole was found to be most advantageous. The 4-thiazole position should either carry 3- or 4-fluorophenyl rings or a 4-pyridyl suitably substituted in the flanking 2-position. Several compounds with single digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained. The compound series display a good PK profile and selectivity over a large number of other targets.

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

Moningka, Remond’s team published research in Bioorganic & Medicinal Chemistry Letters in 30 | CAS: 763120-58-7

Moningka, Remond published the artcileFragment-based lead discovery of a novel class of small molecule antagonists of neuropeptide B/W receptor subtype 1 (GPR7), Safety of 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2020), 30(23), 127510, database is CAplus and MEDLINE.

Here, we report the discovery of a new class of NPBWR1 antagonists identified from a fragment-based screen. Compound 1 (cAMP IC₅₀ = 250μM; LE = 0.29) emerged as an initial hit. Further optimization of 1 by SAR-by-catalog and chem. modification produced 21a (cAMP IC₅₀ = 30 nM; LE = 0.39) with a 6700-fold increase in potency from fragment 1. Somewhat surprisingly, Schild anal. of compound 21a suggested that in vitro inhibition of NPW-mediated effects on upon cAMP accumulation were saturable, and that compound 21a dose-dependently increased [125I]-hNPW23 dissociation rate constants from NPBWR1 in kinetic binding studies. Collectively, these data are inconsistent with a classic surmountable, orthosteric mechanism of inhibition. The benzimidazole inhibitors reported herein may therefore represent a mechanistically differentiated class of compounds with which to form a better appreciation of the pharmacol. and physiol. roles of this central neuropeptide system.

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