887308-25-0

Basic information

• Product Name: N-[5-(5-BenzenesulfonylaMino-6-chloro-pyridin-3-yl)-4-Methyl-thiazol-2-yl]-acetaMide
• Synonyms: N-[5-(5-BenzenesulfonylaMino-6-chloro-pyridin-3-yl)-4-Methyl-thiazol-2-yl]-acetaMide
• CAS NO: 887308-25-0
• Molecular Formula: C₁₇H₁₅ClN₄O₃S₂
• Molecular Weight: 422.909
• EINECS: -0
• Mol File: 887308-25-0.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• CAS DataBase Reference: N-[5-(5-BenzenesulfonylaMino-6-chloro-pyridin-3-yl)-4-Methyl-thiazol-2-yl]-acetaMide(CAS DataBase Reference)
• NIST Chemistry Reference: N-[5-(5-BenzenesulfonylaMino-6-chloro-pyridin-3-yl)-4-Methyl-thiazol-2-yl]-acetaMide(887308-25-0)
• EPA Substance Registry System: N-[5-(5-BenzenesulfonylaMino-6-chloro-pyridin-3-yl)-4-Methyl-thiazol-2-yl]-acetaMide(887308-25-0)

Safety Data

• Hazardous Substances Data: 887308-25-0(Hazardous Substances Data)

Upstream product

• 7336-51-8 2-acetamido-4-methylthiazole 
• 588729-99-1 3-amino-5-bromo-2-chloropyridine 
• 887308-20-5 N-(5-(5-amino-6-chloropyridin-3-yl)-4-methylthiazol-2-yl)acetamide 
• 98-09-9 benzenesulfonyl chloride 

Downstream Products

• 957061-68-6 N-[5-(5-benzenesulphonamido-6-chloropyridin-3-yl)-bromomethylthiazol-2-yl]acetamide 
• 957061-70-0 N-[5-(5-benzenesulphonamido-2-bromo-6-chloropyridin-3-yl)-4-bromomethylthiazol-2-yl]acetamide 
• 957061-71-1 N-[5-(5-benzenesulphonamido-2-bromo-6-chloropyridin-3-yl)-4-(4-methylpiperazin-1-ylmethyl)thiazol-2-yl]acetamide 
• 957061-72-2 N-[5-(5-benzenesulphonamido-6-chloropyridin-3-yl)-4-(4-methylpiperazin-1-ylmethyl)thiazol-2-yl]acetamide 
• 957061-69-7 N-[5-(5-benzenesulphonamido-6-chloropyridin-3-yl)-4-morpholinomethylthiazol-2-yl]acetamide 
• 887308-98-7 N-(5-(2-amino-4-methylthiazol-5-yl)-2-chloropyridin-3-yl)benzenesulfonamide 

Relevant articles and documents

Discovery of (S)-2-amino-N-(5-(6-chloro-5-(3-methylphenylsulfonamido)pyridin-3-yl)-4-methylthiazol-2-yl)-3-methylbutanamide (CHMFL-PI3KD-317) as a potent and selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor

PI3Kδ which is mainly expressed in leukocytes, plays a critical role in B-cell receptor mediated signaling pathway and has been extensively studied as a drug discovery target for B cell malignances such as AML, CLL etc. In this manuscript, we report the discovery, SAR optimization and pharmacological evaluation of a novel series of aminothiazole-pyridine containing PI3Kδ inhibitors. Among them compound 15i (CHMFL-PI3KD-317) displays an IC50 of 6 nM against PI3Kδ in the ADP-Glo biochemical assays. It also exhibits over 10–1500 fold selectivity over other class I, II and III PIKK family isoforms. In addition, in the cellular context, 15i can selectively and potently inhibit PI3Kδ mediated phosphorylation of Akt T308 but not PI3Kα β γ mediated Akt phosphorylation. 15i also exhibits an excellent selectivity profile in the protein kinases including 468 kinases/mutants at the concentration of 1 μM. 15i has acceptable pharmacokinetic properties and can dose-dependently inhibit the tumor growth of AML cell line MOLM14 inoculated xenograft mouse model. The high selectivity and potency makes 15i a potential valuable addition to the current PI3Kδ armory.

THIAZOLE DERIVATIVES AND THEIR USE AS ANTI-TUMOUR AGENTS

The invention concerns thiazole derivatives of Formula (I) or pharmaceutically-acceptable salts thereof, wherein each of R, Ring A, m, R1, R2 and R3 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in therapy, for example in the treatment of disease mediated by a PI3K enzyme and/or a mTOR kinase.