Xia, Liang; Zhang, Yan; Zhang, Jingbo; Lin, Songwen; Zhang, Kehui; Tian, Hua; Dong, Yi; Xu, Heng published the artcile< Identification of novel thiazolo[5,4-b]pyridine derivatives as potent phosphoinositide 3-kinase inhibitors>, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is thiazolopyridine preparation antitumor SAR mol docking phosphoinositide kinase inhibitor; docking analysis; heterocycle; inhibitory potency; phosphoinositide 3-kinase; thiazolo[5,4-b]pyridine.
A series of novel 2-pyridyl, 4-morpholinyl substituted thiazolo[5,4-b]pyridine analogs I [X=CH, N; R1= H, methoxy; R2 = Me, 2,4-difluorophenyl, 5-chloro-2-thienyl, etc.] was designed and synthesized. These thiazolo[5,4-b]pyridines were efficiently prepared in seven steps from com. available substances in moderate to good yields. All of these N-heterocyclic compounds were characterized by NMR and high-resolution mass spectrometry anal. and tested for phosphoinositide 3-kinase (PI3K) enzymic assay. The results indicated that these N-heterocyclic compounds showed potent PI3K inhibitory activity, and the IC50 of a representative compound I [X=N; R1= methoxy; R2= 2,4-difluorophenyl] would reach to 3.6 nm. The structure-activity relationships (SAR) study showed that sulfonamide functionality was important for PI3Kα inhibitory activity, and 2-chloro-4-fluorophenyl sulfonamide I [X=N; R1= methoxy; R2 = 2-chloro-4-fluoro-phenyl] or 5-chlorothiophene-2-sulfonamide I [X=N; R1= methoxy; R2= 5-chloro-2-thienyl] showed potent inhibitory activity with a nanomolar IC50 value. The pyridyl attached to thiazolo[5,4-b]pyridine was another key structural unit for PI3Kα inhibitory potency, and replacement by Ph leaded to a significant decrease in activity. Enzymic Inhibition results showed that compound I [X=N; R1= methoxy; R2= 2,4-difluorophenyl] inhibited PI3Kα, PI3Kγ, or PI3Kδ with a nanomolar IC50 value, but its inhibitory activity on PI3Kβ was approx. 10-fold reduced. Further docking anal. revealed that the N-heterocyclic core of compound I [X=N; R1= methoxy; R2= 2,4-difluorophenyl] was directly involved in the binding to the kinase through the key hydrogen bonds interaction.
Molecules published new progress about Antitumor agents. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics