Category: 724710-02-5

Tng, Jiahui published the artcileAchiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class I HDAC Enzymes and Cancer Cell Proliferation, Name: (1H-Pyrazol-5-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2020), 63(11), 5956-5971, database is CAplus and MEDLINE.

AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clin. trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogs incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC₅₀ 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86(I) was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Mol. modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.

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 C22H32O2, Name: (1H-Pyrazol-5-yl)boronic acid.

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

O’Dowd, Colin R. published the artcileIdentification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors, Synthetic Route of 724710-02-5, the publication is ACS Medicinal Chemistry Letters (2018), 9(3), 238-243, database is CAplus and MEDLINE.

Ubiquitin specific protease 7 (USP7, HAUSP) has become an attractive target in drug discovery due to the role it plays in modulating Mdm2 levels and consequently p53. Increasing interest in USP7 is emerging due to its potential involvement in oncogenic pathways as well as possible roles in both metabolic and immune disorders in addition to viral infections. Potent, novel, and selective inhibitors of USP7 have been developed using both rational and structure-guided design enabled by high-resolution cocrystallog. Initial hits were identified via fragment-based screening, scaffold-hopping, and hybridization exercises. Two distinct subseries are described along with associated structure-activity relationship trends, as are initial efforts aimed at developing compounds suitable for in vivo experiments Overall, these discoveries will enable further research into the wider biol. role of USP7.

ACS 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, Synthetic Route of 724710-02-5.

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

Ochiana, Stefan O. published the artcileSynthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 2. Tadalafil analogs, Related Products of pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(7), 2582-2584, database is CAplus and MEDLINE.

In this Letter we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biol. evaluation of analogs of tadalafil, a human PDE5 inhibitor currently utilized for treatment of erectile dysfunction, and report that these analogs are weak inhibitors of TbrPDEB1.

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, Related Products of pyrazoles-derivatives.

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

Ambati, Srinivasa Rao published the artcileFacile Synthesis of Novel 3-(4-phenylisothiazol-5-yl)-2H-chromen-2-one Derivatives as Potential Anticancer Agents, Related Products of pyrazoles-derivatives, the publication is Journal of Heterocyclic Chemistry (2017), 54(4), 2333-2341, database is CAplus.

A series of 3-(4-phenylisothiazol-5-yl)-2H-chromen-2-one derivatives was efficiently synthesized by straightforward sequential reactions. Tandem Vilsmeier Hack reaction/cyclization/bromination/Suzuki cross-coupling reactions were successfully applied to the preparation of title compounds in good-to-high yields. In the synthetic sequences, 3-chloro-3-(2-oxo-2H-chromen-3-yl)acrylaldehydes react with ammonium thiocyanate to yield the corresponding 3-(isothiazol-5-yl)-2H-chromen-2-ones. These derivatives were brominated with N-bromo succinamide to yield the corresponding regioselective 3-(4-bromoisothiazol-5-yl)-2H-chromen-2-one. Finally, compound 3-(4-bromoisothiazol-5-yl)-2H-chromen-2-one was treated with various phenyl/pyrazole/7H-pyrrolo[2,3-d]pyrimidinyl boronic acids in the presence of K₂CO₃ and Pd catalyst in DMF to yield the corresponding title derivatives All the synthesized compounds were characterized by anal. and spectral studies. All the final compounds were screened against different cancer cell lines (A549, PC3, SKOV3, and B16F10), and among these compounds, 3-(4-phenylisothiazol-5-yl)-2H-chromen-2-one, 6-bromo-3-(4-(4-chlorophenyl)isothiazol-5-yl)2H-chromen-2-one, 6-bromo-3-(4-phenylisothiazol-5-yl)-2H-chromen-2-one , and 3-(4-(7H-pyrrolo[2,3-d]pyrimidine-4-yl)isothiazole-5-yl)-6-bromo-2H-chromen-2-one displayed moderate cytotoxic activity against the tested cell lines.

Journal of Heterocyclic 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, Related Products of pyrazoles-derivatives.

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

Kozlyuk, Natalia published the artcileA fragment-based approach to discovery of Receptor for Advanced Glycation End products inhibitors, Synthetic Route of 724710-02-5, the publication is Proteins: Structure, Function, and Bioinformatics (2021), 89(11), 1399-1412, database is CAplus and MEDLINE.

The Receptor for Advanced Glycation End products (RAGE) is a pattern recognition receptor that signals for inflammation via the NF-κB pathway. RAGE has been pursued as a potential target to suppress symptoms of diabetes and is of interest in a number of other diseases associated with chronic inflammation, such as inflammatory bowel disease and bronchopulmonary dysplasia. Screening and optimization have previously produced small mols. that inhibit the activity of RAGE in cell-based assays, but efforts to develop a therapeutically viable direct-binding RAGE inhibitor have yet to be successful. Here, we show that a fragment-based approach can be applied to discover fundamentally new types of RAGE inhibitors that specifically target the ligand-binding surface. A series of systematic assays of structural stability, solubility, and crystallization were performed to select constructs of the RAGE ligand-binding domain and optimize conditions for NMR-based screening and co-crystallization of RAGE with hit fragments. An NMR-based screen of a highly curated ∼14 000-member fragment library produced 21 fragment leads. Of these, three were selected for elaboration based on structure-activity relationships generated through cycles of structural anal. by X-ray crystallog., structure-guided design principles, and synthetic chem. These results, combined with crystal structures of the first linked fragment compounds, demonstrate the applicability of the fragment-based approach to the discovery of RAGE inhibitors.

Proteins: Structure, Function, and Bioinformatics 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