BIFLUORODIOXALANE-AMINO-BENZIMIDAZOLE KINASE INHIBITORS FOR THE TREATMENT OF CANCER, AUTOIMMUNEINFLAMMATION AND CNS DISORDERS

摘要

The invention relates to a compound of the general formula (I) or a physiologically functional derivative, solvate or salt thereof,;;wherein

A, X, L, Y, R, and RN are as defined herein. The invention further relates to the use of the compounds of formula (I) as a medicament, a pharmaceutical composition comprising them, a method of treatment or prevention of a medical condition entailing the administration thereof, and the use thereof in the manufacture of a medicament for the treatment or prevention of a medical condition, particularly autoimmune inflammatory disorders, CNS disorders, sleeping disorders, or proliferative diseases including cancer. The invention further relates to a specific process for the preparation of said compounds.

主权项

1. A compound of the general formula (I) or a physiologically functional derivative, solvate or salt thereof,wherein
R is independently selected from the group comprising H, halogen, C1-6-alkyl, C1-6-haloalkyl, C1-6-haloalkoxy, OH, C1-6-alkoxy, —S—R′″, —SO—R′″, nitro, —N(R′″)2, —NH(R′″), —NHCO(R′″), —CONH2, —CONH(R″′), —CO(R′″), —COH, —COO(R′″), —COOH, —SO2NH2, —SO2NH(R′″), —SO2(R′″), and —NH—SO2(R′″), wherein in the cases where said group R is C1-6-alkyl, C1-6-haloalkyl, C1-6-haloalkoxy, or C1-6-alkoxy, said group R may be substituted with one or more substituents R″ independently selected from the group comprising H, halogen, OH, nitro, —NH2, —N(C1-6-alkyl)2, —NH(C1-6-alkyl), —NHCO(C1-6-alkyl), —CONH2, —CONH(C1-6-alkyl), —CO(C1-6-alkyl), —COH, —COO(C1-6-alkyl), —COOH, and —CN, and wherein R′″ is independently selected from the group comprising H, C1-6-alkyl, C1-6-haloalkyl, aryl, heteroaryl, cycloalkyl and heterocyclyl; RN is independently selected from the group comprising H, alkyl, haloalkyl, OH, aryl, heteroaryl, cycloalkyl, heterocyclyl, —SO—R′″, —NH2, —N(R′″)2, —NH(R′″), —NHCO(R′″), —CONH2, —CONH(R′″), —CO(R″′), —COH, —COO(R″′), —COOH, —SO2NH2, —SO2NH(R′″), —SO2(R′″), and —NH—SO2(R′″), wherein R″′ is as defined above, wherein in the cases where said group RN is alkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl, said group RN may be substituted with one or more substituents R′″ as defined above; A is independently selected from *—N(Ra)CO—, *—CON(Ra)—, *—SO2N(Ra)—, and *—N(Ra)—SO2—, wherein Ra is selected from H and Cm-alkyl, and wherein * specifies the point of attachment to X; X is independently selected from the group comprising aryl, cycloalkyl, aralkyl, heterocyclyl and heteroaryl, wherein said group X may be substituted with one or more RX independently selected from the group comprising halogen, C1-6-alkyl, C1-6-haloalkyl, C1-6-haloalkoxy, OH, C1-6-alkoxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, —S—C1-6-alkyl, —S—C1-6-haloalkyl, nitro, —NH2, —N(C1-6-alkyl)2, —NH(C1-6-alkyl), —NHCO(C1-6-alkyl), —CONH2, —CONH(C1-6-alkyl), —CO(C1-6-alkyl), —COH, —COO(C1-6-alkyl), —COOH, —SO2NH2, —SO2NH(C1-6-alkyl), —SO2(C1-6-alkyl), —NH—SO2(C1-6-alkyl), C3-6-cycloalkyl, and —CN; L is independently a bond or a linker group selected from the group comprising *—NHCO—, *—CONH—, *—NH—, *—N(C1-4-alkyl)-, *—C═N(C1-4-alkyl)-, *—NH—C1-4-alkyl-, *—C1-4-alkyl-NH—, *—NHCONH—, *—CO—, *—SO2—, Cm-alkyl, *—C1-2-alkyl-O—C1-2-alkyl-, *—NHCO—CH═CH—, *—CH═CH—CONH—, *—SO2NH—, *—NHSO2—, and pyridinyl, wherein * specifies the point of attachment to X; and Y is independently selected from the group comprising H, alkyl, aryl, aralkyl, cycloalkyl, heterocyclyl and heteroaryl, wherein said group Y may optionally be substituted with one or more RY independently selected from the group comprising halogen, C1-6-alkyl, C1-6-haloalkyl, C1-6-haloalkoxy, OH, C1-6-alkoxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, —S—C1-6-alkyl, —S—C1-6-halo alkyl, nitro, —NH2, —N(C1-6-alkyl)2, —NH(C1-6-alkyl), —NHCO(C1-6-alkyl), —CONH2, —CONH(C1-6-alkyl), —CO (C1-6-alkyl), —COH, —COO(C1-6-alkyl), —COOH, —SO2NH2, —SO2NH(C1-6-alkyl), —SO2(C1-6-alkyl), —NH—SO2(C1-6-alkyl), C1-6-alkyl-heterocyclyl, cycloalkyl and —CN.