1-OXO-3-(1H-INDOL-3-YL)-1,2,3,4-TETRAHYDROISOQUINOLINES, METHODS OF PREPARATION THEREOF, COMBINATORY LIBRARY, AND FOCUSED LIBRARY Russian patent published in 2007 - IPC C07D401/04 C07D401/14 A61K31/4725 A61P35/00 

FIELD: organic synthesis.

SUBSTANCE: 1-oxo-3-(1H-indol-3-yl)-1,2,3,4-tetrahydroisoquinolines (including their cis- and trans-isomers) are depicted by following general formulae: (1) and (2), in which R¹, R², and R⁴ independently represent cyclic system substituents selected from hydrogen atom and alkyl; R³ is amino group selected from alkyl, cycloalkyl, and alkyl optionally substituted by aryl, heteroaryl, heterocyclyl, alkoxy, amino, alkylamino, and dialkylamino; R⁵ and R⁶ independently represent amino group substituents selected from hydrogen, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkyl, and alkyl optionally substituted by aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkoxy, amino, alkylamino, dialkylamino, or arylalkylamino; or R⁵ and R⁶, together with nitrogen atom to which they are linked, form optionally substituted aza-heterocycle. Method of preparing compounds 1 consists in reaction of corresponding indol-3-ylmethylamines with homophthalic anhydrides in an organic solvent. Compounds 2 are prepared by treating compounds 1 with thionyl chloride or 1,1'-carbonyldiimidazole to form corresponding derivatives, which are reacted with corresponding amines in an organic solvent. Compounds of invention exhibit proteinkinase inhibiting activities. Combinatory and focused libraries are also provided to reveal leading compounds.

EFFECT: expanded synthetic possibilities in quinoline series and increased choice of proteinkinase inhibitors.

3 cl, 3 tbl, 3 ex