1032759-01-5 | Pyridine-derivatives

Mahajan, Dinesh’s team published research in Journal of Medicinal Chemistry in 63 | CAS: 1032759-01-5

Journal of Medicinal Chemistry published new progress about 1032759-01-5. 1032759-01-5 belongs to pyridine-derivatives, auxiliary class Boronic acid and ester,Boronic acid and ester, name is (6-Amino-5-methylpyridin-3-yl)boronic acid, and the molecular formula is C6H9BN2O2, Recommanded Product: (6-Amino-5-methylpyridin-3-yl)boronic acid.

Mahajan, Dinesh published the artcileDiscovery and Development of SPR519 as a Potent, Selective, and Orally Bioavailable Inhibitor of PI3Kα and mTOR Kinases for the Treatment of Solid Tumors, Recommanded Product: (6-Amino-5-methylpyridin-3-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2020), 63(19), 11121-11130, database is CAplus and MEDLINE.

Herein, we report the identification and preclin. profile of a lead compound 10, (SPR519) as an equally potent dual inhibitor of PI3Kα and mTOR kinases. SPR519 exhibits an EC₅₀ of low sub-micromolar range among various tested cancer cell lines such as A2780 (0.23μM), PC3 (0.48μM), and SKOV3 (0.50μM). When administrated orally, it shows a considerably high plasma exposure (area under curve: 26,858 nM/h at 1 mg/kg) in mice. Moreover, it is found to be safe in animals with a dose of 30 mg/kg BID for 12 days in the dose tolerance study. SPR519 did not show any CYP or hERG liability. The identified lead compound demonstrates significant efficacy and bioavailability in ovarian and colon cancer xenograft models when evaluated for dose-ranging efficacy studies, at a dose as low as 2.5 mg/kg.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Grimstrup, Marie’s team published research in Bioorganic & Medicinal Chemistry Letters in 20 | CAS: 1032759-01-5

Bioorganic & Medicinal Chemistry Letters published new progress about 1032759-01-5. 1032759-01-5 belongs to pyridine-derivatives, auxiliary class Boronic acid and ester,Boronic acid and ester, name is (6-Amino-5-methylpyridin-3-yl)boronic acid, and the molecular formula is C6H9BN2O2, Safety of (6-Amino-5-methylpyridin-3-yl)boronic acid.

Grimstrup, Marie published the artcileNovel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 2, Safety of (6-Amino-5-methylpyridin-3-yl)boronic acid, 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/Pyridine,
Pyridine | C5H5N – PubChem

Hucke, Oliver’s team published research in Journal of Medicinal Chemistry in 57 | CAS: 1032759-01-5

Hucke, Oliver published the artcileMolecular Dynamics Simulations and Structure-Based Rational Design Lead to Allosteric HCV NS5B Polymerase Thumb Pocket 2 Inhibitor with Picomolar Cellular Replicon Potency, Recommanded Product: (6-Amino-5-methylpyridin-3-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2014), 57(5), 1932-1943, database is CAplus and MEDLINE.

The design and preliminary SAR of a new series of 1H-quinazolin-4-one (QAZ) allosteric HCV NS5B thumb pocket 2 (TP-2) inhibitors was recently reported. To support optimization efforts, a mol. dynamics (MD) based modeling work-flow was implemented, providing information on QAZ binding interactions with NS5B. This approach predicted a small but critical ligand-binding induced movement of a protein backbone region which increases the pocket size and improves access to the backbone carbonyl groups of Val 494 and Pro 495. This localized backbone shift was consistent with key SAR results and was subsequently confirmed by X-ray crystallog. The MD protocol guided the design of inhibitors, exploiting novel H-bond interactions with the two backbone carbonyl groups, leading to the first thumb pocket 2 NS5B inhibitor with picomolar antiviral potency in genotype (gt) 1a and 1b replicons (EC₅₀ = 120 and 110 pM, resp.) and with EC₅₀ ≤ 80 nM against gt 2-6.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem