N-(1-(1-BENZYL-4-PHENYL-1H-IMIDAZOL-2-YL)-2,2-DIMETHYLPROPYL)-BENZAMIDE DERIVATIVES AND RELATED COMPOUNDS AS KINESIN SPINDLE PROTEIN (KSP) INHIBITORS FOR TREATING CANCER Russian patent published in 2011 - IPC C07D233/54 C07D401/12 C07D405/12 C07D413/12 C07D417/12 A61K31/4174 A61K31/4178 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazole derivatives of general formula I and pharmaceutically acceptable salts thereof, where R¹ is selected from a group comprising aryl and alkyl, optionally substituted hydroxy; R² is selected from a group comprising hydrogen and alkyl; R³ is selected from a group comprising hydrogen and -X-A, where X is selected from a group comprising -C(O)- and -S(O)₂-; and A is selected from a group comprising hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycle and optionally substituted cycloalkyl, where the optionally substituted groups are substituted with 1-2 substitutes selected from a group comprising alkyl, substituted alkyl, alkoxy, substituted amine which is a -NRR group, substituted aryloxy, heteroaryl, heterocycle, halogen, hydroxy and -S(O)₂-R⁹, where R⁹ is an alkyl; or R¹ and R³ together with a carbon atom bonded to R¹ and a nitrogen atom bonded to R³ form a heterocyclic or substituted heterocyclic group; R⁴ is selected from a group comprising hydrogen, linear alkyl, -alkylene-aminoacyl-, -alkylene-hydroxy-, -[alkylene]_p-nitrogen-containing heterocycle, -[alkylene]_p-nitrogen-containing substituted heterocycle, -[alkylene]_p-nitrogen-containing heteroaryl, -[alkylene]_p-nitrogen-containing substituted heteroaryl and -[alkylene]_p-NR¹⁰R¹¹, where p equals 0 or 1, the alkylene contains 1-5 carbon atoms and can have 1 or 2 substitutes selected from a group comprising amine, hydroxy and halogen, aminoacyl relates to a group -C(O)NRR, where each R is independently selected from a group comprising hydrogen and alkyl, R¹⁰ and R¹¹ are independently selected from a group comprising hydrogen, alkyl, substituted alkyl, -S(O)₂-alkyl, substituted aryl, substituted heteroaryl, cycloalkyl, or when R¹⁰ is hydrogen, R¹¹ is hydroxy, alkoxy or substituted alkoxy; or when R¹ and R³ together with carbon and nitrogen atoms respectively bonded to them do not form a heterocyclic or a substituted heterocyclic group, R³ and R⁴ together with a nitrogen atom to which they are bonded form a spiro-condensed heterocyclic group; R⁵ is selected from a group comprising L-A¹, where L is selected from a group comprising C₁-C₅alkylene, where the alkylene is defined above; and A¹ is selected from a group comprising aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle; and one of R⁶ or R⁷ is selected from a group comprising aryl and heteroaryl, each of which can optionally be substituted with -(R⁸)_m, where m equals a whole number from 1 to 2, and the other of R⁶ or R⁷ is selected from a group comprising hydrogen, halogen and alkyl; or R⁶ as well as R⁷ denotes hydrogen; R⁸ is selected from a group comprising cyano, alkyl, -CF₃, alkoxy, halogen, where alkyl, aryl, aryloxy, cycloalkyl, heterocycle, heteraryl and substituted alkyl, aryl, aryloxy, cycloalkyl, heterocycle and heteroaryl are described in claim 1. The invention also relates to specific compounds, a pharmaceutical composition based on the compound of formula I, a method of inhibiting KSP and use of the composition to prepare a medicinal agent.

EFFECT: novel imidazole derivatives are useful as kinesin spindle protein inhibitors for treating cancer.

25 cl, 27 ex