Protein Kinase Inhibitors (Variants), Use Thereof in Treating Oncological Diseases and a Pharmaceutical Composition Based Thereon
AssigneeObshchestvo s ogranichennoy otvetstvennostyou "Fusion Pharma"
InventorsGermes G. CHILOV, Ilya Y. TITOV
Life of this patent
Estimating the term…
Abstract
The present invention relates to the treatment of oncological, chronic inflammatory and similar diseases with the aid of new families of chemical compounds having improved efficiency with regard to the inhibition of Abl kinase and mutant forms thereof, as well as other therapeutically significant kinases. It describes protein kinase inhibitors in the form of compounds of general formula (I) and compounds of general formula (II), or a tautomer, an individual isomer, a mixture of isomers, a pharmaceutically acceptable salt, a solvate or a hydrate thereof.
Claims20
A compound of Formula I:
- wherein:
- X1 represents N, CRt1;
- X2 represents N, CRt2, X3 represents N, CRt3, X4 represents N, CH and wherein X1, X2, X3 and X4 are selected independently;
- Rt2 represents —H, halo, —COOH, —CH3, —CH2CH3, —OH, —OCH3, —OCH2CH3, —CN, —CH2OH;
- Rt2 represents —H, halo, —CH3, —CH2CH3, —OH, —OCH3, —OCH2CH3, —CN, CH2OH, —NH2;
- Rt3 represents —H, —S(O)rR4, —CN, —COOH, —CONH2, —COOCH3, —COOCH2CH3;
- ring A represents phenyl or 6-membered heteroaryl in which heteroaryl comprising 1-2 heteroatoms selected from N, optionally substituted by 1-4 Ra groups;
- ring B represents phenyl or 5- or 6-membered heteroaryl cycle which comprising 1-2 heteroatoms, selected from N, S, optionally substituted by 1-5 Rb groups;
- Ra and Rb are independently selected from —H, halo, —CN, —R6, —OR4, —NR4R5. —C(O)YR4, —S(O)rR4, —SO2NR4R5, —NR4SO2NR4R5, wherein Y is independently selected from chemical bond, —O—, —S—, —NR5—;
- L1 represents NR3C(O) or C(O)NR3;
- R3, R4 and R5 are independently selected from H, C1-C6-alkyl,
- alternatively NR4R3 group may represent 5- or 6-membered saturated or aromatic ring;
- R6 at each occurrence is independently selected from C1-C6-alkyl optionally substituted by C1-C6-alkyl or 5-6 membered heterocyclyl which can further contain C1-C6 alkyl substituent;
- r is 0;
- or a pharmaceutically acceptable salt, solvate or hydrate.
The compound of claim , wherein in Formula I:
- Rt2═—H.
A compound of the Formula II:
- wherein:
- Z represents CH;
- X1 represents CRt1;
- X2 represents CRt2, X3 represents CRt3, X4 represents CH wherein X1, X2, X3 and X4 are selected independently;
- Rt1 represents —H;
- Rt2 represents —H, —F;
- Rt3 represents —H, —F;
- ring A represents phenyl or 6-membered heteroaryl cycle, in which heteroaryl comprises 1-2 heteroatoms, selected from N, optionally substituted by 1-4 Ra groups
- ring B represents phenyl or 5- or 6-membered heteroaryl cycle, in which heteroaryl comprises 1-2 heteroatoms, selected from N, S, optionally substituted by 1-5 Rb groups;
- Ra and Rb are independently selected from —H, halo, —CN, —R6, —OR4, —NR4R5, —C(O)YR4, —S(O)rR4, —SO2NR4R5, where Y is independently selected from chemical bond, —NR5—;
- L1 represents NR3C(O) or C(O)NR3;
- R3, R4 and R5 are independently selected from H, C1-C6-alkyl,
- alternatively NR4R5 group may represent 6-membered saturated ring;
- R6 at each occurrence is independently selected from C1-C6-alkyl, optionally substituted by C1-C6-alkyl or 5-6 membered heterocyclyl which can further contain C1-C6 alkyl substituent;
- r is 0;
- m is 1;
- p is 1 or 2;
- or a pharmaceutically acceptable salt, solvate or hydrate.
Dependencies are inferred from the claim text.