763120-58-7 | Page 9 of 9 | pyrazoles-derivatives

Cheung, Atwood K.’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, HPLC of Formula: 763120-58-7.

Cheung, Atwood K. published the artcileDiscovery of Small Molecule Splicing Modulators of Survival Motor Neuron-2 (SMN2) for the Treatment of Spinal Muscular Atrophy (SMA), HPLC of Formula: 763120-58-7, the publication is Journal of Medicinal Chemistry (2018), 61(24), 11021-11036, database is CAplus and MEDLINE.

Spinal muscular atrophy (SMA), a rare neuromuscular disorder, is the leading genetic cause of death in infants and toddlers. SMA is caused by the deletion or a loss of function mutation of the survival motor neuron 1 (SMN1) gene. In humans, a second closely related gene SMN2 exists, however it codes for a less stable SMN protein. In recent years, significant progress has been made toward disease modifying treatments for SMA by modulating SMN2 pre-mRNA splicing. Herein, we describe the discovery of LMI070/branaplam, a small mol. that stabilizes the interaction between the spliceosome and SMN2 pre-mRNA. Branaplam (1) originated from a high-throughput phenotypic screening hit, pyridazine 2, and evolved via multi-parameter lead optimization. In a severe mouse SMA model, branaplam treatment increased full-length SMN RNA and protein levels, and extended survival. Currently, branaplam is in clin. studies for SMA.

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

Deng, Huayun’s team published research in Bioorganic & Medicinal Chemistry Letters in 22 | 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 C3H5BN2O2, Application of 1H-Pyrazole-4-boronic acid.

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.

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

Cheng, Hengmiao’s team published research in Bioorganic & Medicinal Chemistry Letters in 23 | CAS: 763120-58-7

Cheng, Hengmiao published the artcileStructure-based design, SAR analysis and antitumor activity of PI3K/mTOR dual inhibitors from 4-methylpyridopyrimidinone series, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(9), 2787-2792, database is CAplus and MEDLINE.

PI3K, AKT and mTOR, key kinases from a frequently dysregulated PI3K signaling pathway, have been extensively pursued to treat a variety of cancers in oncol. Clin. trials of PF-04691502, a highly potent and selective ATP competitive kinase inhibitor of class 1 PI3Ks and mTOR, from 4-methylpyridopyrimidinone series, led to the discovery of a metabolite with a terminal carboxylic acid, PF-06465603. This paper discusses structure-based drug design, SAR and antitumor activity of the MPP derivatives with a terminal alc., a carboxylic acid or a carboxyl amide e. g., I.

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

Ryu, Jae Wook’s team published research in Bioorganic & Medicinal Chemistry Letters in 21 | CAS: 763120-58-7

Ryu, Jae Wook published the artcileDesign and synthesis of triazolopyridazines substituted with methylisoquinolinone as selective c-Met kinase inhibitors, Synthetic Route of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(23), 7185-7188, database is CAplus and MEDLINE.

A series of triazolopyridazines substituted with methylisoquinolinone, e.g. I (R = Ph, pyrrolidin-1-yl, thiazol-3-yl, 3-FC₆H₄), were designed and synthesized. Some of the triazolopyridazines strongly inhibited c-Met kinase and showed good anti-proliferative activity against a panel of c-Met-amplified gastric cancer cell lines (MKN-45, SNU-5 and Hs746T).

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

Johns, Brian A.’s team published research in Bioorganic & Medicinal Chemistry Letters in 17 | CAS: 763120-58-7

Johns, Brian A. published the artcilePyrazolo[1,5-a]pyridine antiherpetics: Effects of the C3 substituent on antiviral activity, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2007), 17(10), 2858-2862, database is CAplus and MEDLINE.

A recently disclosed series of pyrazolo[1,5-a]pyridine inhibitors of herpes virus replication has been closely examined herein for effects of the C3 substituent on antiviral activity. Significant changes in activity are observed by alterations of the heteroatom basicity and orientation of the group at C3. These results in combination with previous studies have served to further elaborate the minimal pharmacophore required for potency of this novel series of antiviral agents. During the course of these studies, several novel synthetic approaches were developed and are described.

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

Bonazzi, Simone’s team published research in Journal of Medicinal Chemistry in 63 | CAS: 763120-58-7

Bonazzi, Simone published the artcileDiscovery of a Brain-Penetrant ATP-Competitive Inhibitor of the Mechanistic Target of Rapamycin (mTOR) for CNS Disorders, Quality Control of 763120-58-7, the publication is Journal of Medicinal Chemistry (2020), 63(3), 1068-1083, database is CAplus and MEDLINE.

Recent clin. evaluation of everolimus for seizure reduction in patients with tuberous sclerosis complex (TSC), a disease with overactivated mechanistic target of rapamycin (mTOR) signaling, has demonstrated the therapeutic value of mTOR inhibitors for central nervous system (CNS) indications. Given that everolimus is an incomplete inhibitor of the mTOR function, we sought to develop a new mTOR inhibitor that has improved properties and is suitable for CNS disorders. Starting from an inhouse purine-based compound, optimization of the physicochem. properties of a thiazolopyrimidine series led to the discovery of the small mol. 7, a potent and selective brain-penetrant ATP-competitive mTOR inhibitor. In neuronal cell-based models of mTOR hyperactivity, 7 corrected the mTOR pathway activity and the resulting neuronal overgrowth phenotype. The new mTOR inhibitor 7 showed good brain exposure and significantly improved the survival rate of mice with neuronal-specific ablation of the Tsc1 gene. These results demonstrate the potential utility of this tool compound to test therapeutic hypotheses that depend on mTOR hyperactivity in the CNS.

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

Kozlyuk, Natalia’s team published research in Proteins: Structure, Function, and Bioinformatics in 89 | CAS: 763120-58-7

Proteins: Structure, Function, and Bioinformatics 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.

Kozlyuk, Natalia published the artcileA fragment-based approach to discovery of Receptor for Advanced Glycation End products inhibitors, Synthetic Route of 763120-58-7, 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.

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

Bauer, Udo’s team published research in Bioorganic & Medicinal Chemistry Letters in 22 | CAS: 763120-58-7

Bauer, Udo published the artcileDiscovery of 4-hydroxy-1,6-naphthyridine-3-carbonitrile derivatives as novel PDE10A inhibitors, Application In Synthesis of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(5), 1944-1948, database is CAplus and MEDLINE.

A series of 1,6-naphthyridine-based compounds, e.g., I (R¹ = OEt, Cl, CH₂OH, morpholinomethyl, etc.), was synthesized as potent phosphodiesterase 10A (PDE10A) inhibitors. For example, (bromophenyl)naphthyridinecarbonitrile II reacted with [2-(trifluoromethoxy)phenyl]boronic acid in the presence of PPh₃/Pd(OAc)₂/Na₂CO₃ in THF/H₂O and heated for 30 min to 150°C in a microwave oven to give the biphenyl naphthyridine III. Structure-based chem. modifications of the discovered chemotype served to further improve potency and selectivity over DHODH, laying the foundation for future optimization efforts.

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