Departamento de Química Orgánica, Facultade de Química, Universidade de Vigo, Lagoas-Marcosende, 36310 Vigo, Spain.
Org Biomol Chem. 2012 Mar 14;10(10):2101-12. doi: 10.1039/c2ob06695e. Epub 2012 Jan 30.
A series of 7,12-dihydroindolo[3,2-d][1]benzazepine-6(5H)-ones (paullones) substituted at C9/C10 (Br) and C2 (Me, CF(3), CO(2)Me) have been synthesized by a one-pot Suzuki-Miyaura cross-coupling of an o-aminoarylboronic acid and methyl 2-iodoindoleacetate followed by intramolecular amide formation. Other approaches to the paullone scaffold based on Pd-catalyzed C-H activation were unsuccessful. In vitro enzymatic assay with recombinant human SIRT-1 indicated a strong inhibitory profile for the series, in particular the analogue with a methoxycarbonyl group at C2 and a bromine at C9. These compounds are, in general, inducers of granulocyte differentiation of the U937 acute leukemia cell line and cause a marked increase in pre-G1 of the cell cycle.
一系列 7,12-二氢吲哚并[3,2-d][1]苯并氮杂卓-6(5H)-酮（paullones）在 C9/C10（Br）和 C2（Me、CF3、CO2Me）处取代，通过邻氨基芳基硼酸和甲基 2-碘吲哚乙酸的一锅铃木-宫浦交叉偶联反应，然后进行分子内酰胺形成。基于 Pd 催化的 C-H 活化的其他方法未能成功合成 paullone 支架。用重组人 SIRT-1 进行的体外酶测定表明，该系列具有很强的抑制作用，特别是在 C2 处具有甲氧基羰基和 C9 处具有溴的类似物。这些化合物通常是 U937 急性白血病细胞系粒细胞分化的诱导剂，并导致细胞周期的预 G1 期明显增加。
