Day: November 24, 2022

Wirth, Franziska published the artcileCdc42 in osterix-expressing cells alters osteoblast behavior and myeloid lineage commitment, Application of 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Bone (New York, NY, United States) (2021), 116150, database is CAplus and MEDLINE.

Osteoblasts are not only responsible for bone formation. They also support hematopoiesis. This requires responding to cues originating from several signaling pathways, a task performed by Rho GTPases. We therefore examined several transgenic mouse models and used inhibitors of Cdc42 in vitro. Deletion of Cdc42 in vivo using the Osterix promoter suppressed osteoblast function, while its deletion in differentiating osteoblasts using the Collagen-伪1(I) promoter decreased osteoblast numbers In both cases, bone mineral d. diminished confirming the importance of Cdc42. Evaluation of hematopoiesis revealed that deletion of Cdc42 using the Osterix, but not the Collagen-伪1(I) promoter increased the common myeloid progenitors (CMPs) in the bone marrow as well as the erythrocytes and the thrombocytes/platelets in peripheral blood. Causality between Cdc42 loss in early osteoblasts and increased myelopoiesis was confirmed in vitro. Work in vitro supported the conclusion that interleukin-4 mediated the increase in myelopoiesis. Thus, Cdc42 is required for healthy bone through regulation of bone formation in Osterix-expressing osteoblasts and the number of osteoblasts in differentiating osteoblasts. In addition, its expression in early osteoblasts/stromal cells modulates myelopoiesis. This highlights the importance of osteoblasts in regulating hematopoiesis.

Bone (New York, NY, United States) 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 C10H10O2, Application of 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

Jiang, Jian-kang published the artcileDiscovery of 3-(4-sulfamoylnaphthyl)pyrazolo[1,5-a]pyrimidines as potent and selective ALK2 inhibitors, Synthetic Route of 1416437-27-8, the publication is Bioorganic & Medicinal Chemistry Letters (2018), 28(20), 3356-3362, database is CAplus and MEDLINE.

The pyrazolo[1,5-a]pyrimidine LDN-193189 is a potent inhibitor of activin receptor-like kinase 2 (ALK2) but is nonselective for highly homologous ALK3 and shows only modest kinome selectivity. Herein, we describe the discovery of a novel series of potent and selective ALK2 inhibitors by replacing the quinolinyl with a 4-(sulfamoyl)naphthyl, yielding ALK2 inhibitors that exhibit not only excellent discrimination vs. ALK3 but also high kinome selectivity. In addition, the optimized compound 23 demonstrates good ADME and in vivo pharmacokinetic properties.

Bioorganic & Medicinal Chemistry Letters published new progress about 1416437-27-8. 1416437-27-8 belongs to pyrazoles-derivatives, auxiliary class Other Aromatic Heterocyclic,Boronic acid and ester,Boronate Esters,Boronic acid and ester, name is 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyrimidine, and the molecular formula is C12H16BN3O2, Synthetic Route of 1416437-27-8.

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

Zhao, Xinge published the artcileDiscovery of novel Bruton’s tyrosine kinase (BTK) inhibitors bearing a pyrrolo[2,3-d]pyrimidine scaffold, Application In Synthesis of 724710-02-5, the publication is Bioorganic & Medicinal Chemistry (2015), 23(4), 891-901, database is CAplus and MEDLINE.

A series of novel reversible BTK inhibitors was designed based on the structure of the recently reported preclin. drug RN486. Knowledge of the binding mode of RN486 led to the design of new inhibitors that utilized pyrrolo[2,3-d]pyrimidine to conformationally restrain key pharmacophoric groups within the mol. Comprehensive SAR was disclosed and the most promising compound 4x displayed superior activity both in BTK enzyme (IC₅₀ = 4.8 nM) and cellular inhibition (IC₅₀ = 17 nM) assays to that of RN486.

Bioorganic & 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 C5H8N2O, Application In Synthesis of 724710-02-5.

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

Liu, Qingyun published the artcileBismuth(III)-Promoted Trifluoromethylthiolation of Pyrazolin-5-ones with Trifluoromethanesulfenamide, COA of Formula: C10H9ClN2O, the publication is ACS Omega (2017), 2(11), 7755-7759, database is CAplus and MEDLINE.

An efficient and facile method for the synthesis of trifluoromethylthiolated 5-hydroxy-1H-pyrazole derivatives by reaction of pyrazolin-5-ones with trifluoromethanesulfenamide (PhNHSCF₃) in the presence of BiCl₃ was developed.

ACS Omega 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, COA of Formula: C10H9ClN2O.

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

Zhang, Shiyan published the artcileDiscovery of a 2-pyridinyl urea-containing compound YD57 as a potent inhibitor of apoptosis signal-regulating kinase 1 (ASK1), Category: pyrazoles-derivatives, the publication is European Journal of Medicinal Chemistry (2020), 112277, database is CAplus and MEDLINE.

Inhibition of MAP3K kinase ASK1 has been an attractive strategy for the treatment of nonalcoholic steatohepatitis and multiple sclerosis, among others. Herein, we reported the discovery of 2-pyridinyl urea-containing compound 14l (YD57) as a potent, small-mol. inhibitor of ASK1. 14l was selective against MAP3K kinases ASK2 and TAK1 (>140-fold), while it also inhibited several cell cycle regulating kinases with IC₅₀ values in a range of 90-400 nM (<20-fold selectivity). As a consequence, 14l had stronger apoptosis induction, more potent G1 cell cycle arrest activities, and lower IC₅₀ value of cell growth inhibition than that of GS4997 in HepG2 cancer cell line. On the other hand, 14l did not inhibit ASK1 and p38 phosphorylation in intact cells. We reason that the multi-target effects of 14l likely neutralized the activities caused by inhibition of cellular ASK1. Future studies of these ASK1 inhibitors should pay close attention to their kinome selectivity profile.

European Journal of Medicinal Chemistry published new progress about 137837-55-9. 137837-55-9 belongs to pyrazoles-derivatives, auxiliary class Other Aromatic Heterocyclic,Amine, name is Pyrazolo[1,5-a]pyridin-3-amine, and the molecular formula is C65H82N2O18S2, Category: pyrazoles-derivatives.

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

Duan, Yu-Lai published the artcileZirconium and hafnium complexes bearing pyrrolidine derived salalen-type {ONNO} ligands and their application for ring-opening polymerization of lactides, HPLC of Formula: 4551-69-3, the publication is Dalton Transactions (2017), 46(34), 11259-11270, database is CAplus and MEDLINE.

The reactions of pyrrolidine derived salalen-type {ONNO} ligands (S)-L^1-3-H₂ with 1 equivalent M(OⁱPr)₄(HOⁱPr) (M = Zr or Hf) in di-Et ether yielded complexes [L^1-3M(OⁱPr)₂] (L = L¹, M = Zr (1); L = L², M = Zr (2), Hf (3); L = L³, M = Zr (4), Hf (5)). All of these complexes were well characterized by NMR spectroscopy, elemental analyses and single-crystal x-ray anal. in the case of complexes 1 and 3–5. X-ray structural determination revealed that these complexes were analogous mononuclear species and had a similar structure in which the metal centers were six-coordinated to two oxygen atoms and two nitrogen atoms of one ligand and two oxygen atoms of two isopropoxy groups. All of these complexes efficiently initialized the ring-opening polymerization of lactides to afford polymers with controlled mol. weight and narrow polydispersity. Furthermore, the ring-opening polymerization of rac-lactide catalyzed by complexes 1–5 afforded isotactic-enriched polymers in solution (P_m = 0.74-0.80) and under melt conditions (P_m = 0.63-0.72).

Dalton Transactions 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, HPLC of Formula: 4551-69-3.

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

Zhang, Qiangsheng published the artcileThe discovery of SKLB-0335 as a paralog-selective EZH2 covalent inhibitor, COA of Formula: C7H11N3O2, the publication is Chemical Communications (Cambridge, United Kingdom) (2021), 57(24), 3006-3009, database is CAplus and MEDLINE.

By targeting the unique Cys663 of EZH2, SKLB-0335 displayed high paralog-selectivity on EZH2. Biochem. studies showed that SKLB-0335 was covalently bind to EZH2 at its S-adenosylmethionine (SAM) pocket and inhibited H3K27Me3. SKLB-0335 was an effective chem. probe with which to further investigate the specific biol. functions of EZH2.

Chemical Communications (Cambridge, United Kingdom) 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 C7H6N2O2S, COA of Formula: C7H11N3O2.

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

Zheng, Yan-qiu published the artcileCDC42 inhibitor ML141 suppresses laryngeal cancer Hep-2 cell proliferation, Related Products of pyrazoles-derivatives, the publication is Xiandai Shengwuyixue Jinzhan (2016), 16(4), 644-646, 651, database is CAplus.

Objective: Investigating the effect of CDC42 inhibitor ML141 on Hep-2 cell proliferation to provide new targets for mol. therapy of laryngeal cancer. Methods: Hep-2 cells were cultured in vitro. Real-time PCR was used to identify the expression of CDC42 in Hep-2 cell. GLISA was carried out to detect the changes in activation of CDC42 in Hep-2 cell treated with ML141. CCK8 assay was used to detect the effect of ML141 on Hep-2 cell proliferation. Results: 1. The result of Real-time PCR showed that CDC42 gene was differentially expressed in Hep-2 cells, which was consistent with the results of the whole genome profiling (P < 0.001). 2. The result of GLISA showed that epidermal growth factor (EGF) could increase the activation of CDC42 in Hep-2 cell but ML141 could inhibit its activation significantly (p < 0.001). 3. The result of CCK8 showed that the proliferation of Hep-2 cell was significantly inhibited by treating with ML141 after 24 h, 48 h and 72 h compared with control group (P < 0.001). Conclusion: CDC42 inhibitor ML141 could inhibit the proliferation of Hep-2 cell. ML141 might have the potential to become the new anti-cancer drug, which provided a new target point for mol. therapy of laryngeal cancer.

Xiandai Shengwuyixue Jinzhan 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 C16H24BF4Ir, Related Products of pyrazoles-derivatives.

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

Deng, Huayun published the artcileThieno[3,2-b]thiophene-2-carboxylic acid derivatives as GPR35 agonists, Application of 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(12), 4148-4152, database is CAplus and MEDLINE.

The optimization of a series of thieno[3,2-b]thiophene-2-carboxylic acid derivatives for agonist activity against the GPR35 is reported. Compounds were optimized to achieve 尾-arrestin-biased agonism for developing probe mols. that may be useful for elucidating the biol. and physiol. of GPR35. Compound 13 was identified to the most potent GPR35 agonist, and compounds 30 and 36 exhibited the highest efficacy to cause 尾-arrestin translocation.

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

Zhang, Yonghong published the artcileHighly Efficient Bronsted Acidic Ionic Liquid Promoted Direct Diazenylation of Pyrazolones with Aryltriazenes under Mild Conditions, Product Details of C10H9ClN2O, the publication is Asian Journal of Organic Chemistry (2017), 6(1), 102-107, database is CAplus.

The first Bronsted acidic ionic liquid (IL) promoted reaction of 5-pyrazolones with aryltriazenes to prepare arylazopyrazolones is described. The reaction was carried out with the aryltriazenes as diazotizing agents, water as the solvent, and the ionic liquid as the promoter at room temperature under air and metal-free conditions. The desired products were obtained in good to excellent yields. Notably, a gram-scale experiment and a late-stage diazenylation reaction of a pharmaceutical derivative also furnished the desired products under mild conditions.

Asian Journal of Organic Chemistry 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 C25H47NO8, Product Details of C10H9ClN2O.

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