Synthesis of a staurosporine analogue possessing a 7-azaindole unit instead of an indole moiety

The synthesis of a new staurosporine analogue possessing a 7-azaindole unit instead of an indole moiety is described. This synthesis could be achieved by coupling a sugar moiety previously tosylated in 2′ position to the azaindolocarbazole aglycone. Nucleophilic substitution on the carbon bearing the tosyl group yielded to the key cyclization leading to a compound in which the carbohydrate part is linked to both indole and azaindole nitrogen

A three-step synthesis from rebeccamycin of an efficient checkpoint kinase 1 inhibitor.

International audienceRebeccamycin derivative 1 bearing a sugar moiety linked to both indole nitrogens and an amino substituent on the carbohydrate unit was synthesized in three steps from the bacterial metabolite. This compound was found to be a highly potent checkpoint kinase 1 inhibitor with an IC50 value of 2.8 nM

Synthesis of pyridino[3',2' :4,5]pyrrolo[3,2-g]pyrrolo-[3,4-e]indolizin-1,3-dione and pyrrolo[3,2-c]pyrazole skeletons

A three step synthesis of an isogranulatimide analogue, in which the imidazole moiety is replaced by a pyrrole unit and the indole heterocycle is replaced by a 7-azaindole moiety is described. Moreover, a novel synthetic pathway to the pyrrolo[3,2-c]pyrazole skeleton is reporte

Synthesis and biological activities of aminopyrimidyl-indoles structurally related to meridianins

International audienceThe synthesis of new meridianin derivatives substituted at the C-5 position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. These compounds were tested for their kinase inhibitory potencies toward five kinases (CDK5/p25, CK1δ/ε, GSK-3α/β, Dyrk1A and Erk2) as well as their in vitro antiproliferative activities toward a human fibroblast primary culture and two human solid cancer cell lines (MCF-7 and PA 1

Synthesis of dipyrrolo [3,4-a:3,4-c]carbazole-1,3,4,6-tetraones bearing a sugar moiety.

The synthesis of a series of dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones, structurally related to the G2 checkpoint inhibitor granulatimide and bearing a sugar moiety, is described. Substitutions were carried out at the 6-position of the glycosyl unit to lead to an amino substituent as observed in many biologically active compounds such as anthracyclins or staurosporine

Synthesis and biological evaluation of diversely substituted indolin-2-ones

International audienceThe synthesis of indolin-2-one derivatives substituted in the 3-position by an aminomethylene group bearing either an ornithine or a lysine residue is described. The inhibitory activities of these compounds toward a panel of eight kinases were examined. Furthermore, the antibacterial activities of the prepared compounds were tested against two Gram-positive bacteria Bacillus cereus and Streptomyces chartreusis, a Gram-negative bacterium Escherichia coli and a yeast Candida albicans

Synthesis of aminopyrimidylindoles structurally related to meridianins

The synthesis of new meridianin derivatives substituted at the C-5′ position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. The 2-aminopyrimidine ring was obtained via a Bredereck synthesis. Aryl groups were introduced by Suzuki cross-coupling after bromination of the 2-aminopyrimidine ring at the C-5′ positio

Synthesis of glycosyl-isoindigo derivatives

The synthesis of 1-(β--glucopyranosyl)-isoindigo from commercially available indoline is described. The synthetic pathway used allowed the substitution of the aromatic moiety by either electron donor or acceptor substituent

Synthesis and antiproliferative activities of indolin-2-one derivatives bearing amino acid moieties.

A convenient synthesis of indolin-2-ones substituted in the 3 position by an aminomethylene group bearing different amino acid moieties is described. Their antiproliferative activities were evaluated toward a panel of human solid tumor cell lines (PC 3, DLD-1, MCF-7, M4 Beu, A549, PA 1) and healthy cell lines (a murine fibroblast L929 and a human fibroblast primary culture

Synthesis, in vitro antiproliferative activities, and Chk1 inhibitory properties of dipyrrolo[3,4-a:3,4-c]carbazole triones.

The syntheses of dipyrrolo[3,4-a:3,4-c]carbazole-1,4,6-triones and dipyrrolo[3,4-a:3,4-c]carbazole-3,4,6-triones are reported. These compounds can be considered as granulatimide analogues in which a maleimide replaces the imidazole moiety and a five-membered lactam ring replaces the upper maleimide. The Chk1 inhibitory properties of the more soluble compounds have been evaluated and their in vitro antiproliferative activities toward three tumor cell lines: murine leukemia L1210, and human colon carcinoma HT29 and HCT116. Due to their insolubility, the biological activities of the other compounds in this series could not be evaluated. All the tested compounds proved to be potent Chk1 inhibitor