RU2006141096A - MONOCYCLIC HETEROCYCLES INHIBITING KINASE - Google Patents

Claims (18)

1. The compound having the formula II:

and its enantiomers, diastereomers, hydrates, solvates or pharmaceutically acceptable salts, where each R ² independently represents H, halogen, cyano, NO ₂ , OR ⁵ , NR ⁶ R ⁷ , alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocyclo, arylalkyl, substituted arylalkyl, heterocycloalkyl or substituted heterocycloalkyl; B represents O, S, SO or SO ₂ ; W and X each independently represents C or N; n has a value from 0 to 4 if W and X both represent C, from 0 to 3 if one of X and W represents N, and from 0 to 2 if X and W both represent N; R ³ , R ⁵ , R ⁶ and R ^{7 are} independently selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo or substituted heterocycle ; R ⁴ represents a possibly substituted 5-6 membered heteroaryl containing a nitrogen atom, provided that (a) if R ⁴ is pyridyl, R ^{4 is} not substituted with both hydroxy and methoxy groups; and (b) if R ⁴ is pyrimidinyl, it is not substituted = O; And selected from the following compounds of formulas:

where D represents S or O; m has a value from 0 to 6; R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ and R ^{27 are} independently selected from H, halogen, NR ³⁰ R ³¹ , OR ³² , CO ₂ R ³³ , SO ₂ R ³⁶ . alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —CN, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl or substituted heterocycloalkyl; R ²⁸ and R ^{29 are} independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, or taken together, they form a carbocyclic or heterocyclic ring consisting of from 3 to 8 atoms; and R ³⁰ , R ³¹ , R ³² , R ³³ and R ^{36 are} independently selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, alkoxycarbonyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl , heterocyclo, substituted heterocyclo, heterocycloalkyl or substituted heterocycloalkyl. 2. The compound according to claim 1, where R ² represents H, C ₁ -C ₄ alkyl, halogen, or halogenated. 3. The compound according to claim 1, where R ⁴ represents an optionally substituted pyridinone, pyridyl, pyridyl-N-oxide or pyrazolyl. 4. The compound according to claim 5, where R ^{4 is} substituted by oxygen, phenyl, C ₁ -C ₄ alkyl or halogen. 5. The compound according to claim 1, where b represents O. 6. The compound according to claim 1, where a is

or

7. The compound according to claim 6, in which R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ and R ^{22 are} independently selected from H, alkyl, alkenyl, alkynyl, halogen, cycloalkyl, heterocycloalkyl, or NR ⁴¹ R ⁴² , where R ⁴¹ and R ^{42 are} independently selected from H, lower alkyl, substituted lower alkyl, hydroxyalkyl, aminoalkyl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, or substituted heteroaryl. 8. The compound of claim 7, wherein A is pyridine substituted with —NR ⁴¹ R ⁴² , halogen, or C ₁ -C ₄ alkyl. 9. The compound of claim 8, where C ₁ -C ₄ alkyl is substituted by hydroxyl, hydroxyalkylamino, alkylamino, aminoalkylamino, or heteroarylalkyl. 10. The compound according to claim 7, where R ⁴¹ and R ⁴² each independently represents H, methyl, ethyl, propyl, butyl, phenyl, or benzyl. 11. The compound of claim 6, wherein the pyridine is substituted with a phenyl group, optionally substituted with CONH ₂ , methyl, aminoethyl, hydroxyethyl, —CONHCH ₂ CH ₂ NHCH ₃ , or CH ₂ CONH ₂ ; pyridine, or piperazine. 12. The compound of claim 7, wherein A is pyrimidine substituted with —NR ⁴¹ R ⁴² . 13. The compound of claim 12, wherein R ⁴¹ and R ⁴² are H or methyl. 14. The compound according to claim 1 of formula IV:

where R ² represents halogen or H; R ³ represents H; R ⁴ is optionally substituted pyrazole or optionally substituted pyridyl, optionally substituted pyridinone or pyridine-N-oxide, and A is optionally substituted pyridyl. 15. The compound of claim 14, wherein R ⁴ is optionally substituted with pyridinone or pyridine-N-oxide. 16. The compound according to claim 1, having an IC ₅₀ value of less than about 1.0 μM. 17. A pharmaceutical composition for treating cancer comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier. 18. The compound according to claim 1 of formula IV:

where A is selected from the following compounds of formulas:

R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ and R ^{27 are} independently selected from H, halogen, NR ³⁰ R ³¹ , OR ³² , CO ₂ R ³³ , SO ₂ R ³⁶ , alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —CN, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl or substituted heterocycloalkyl; R ²⁸ and R ^{29 are} independently selected from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, or taken together, they form a carbocyclic or heterocyclic ring consisting of from 3 to 8 atoms; R ³⁰ , R ³¹ , R ³² , R ³³ and R ^{36 are} independently selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, alkoxycarbonyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl , heterocyclo, substituted heterocyclo, heterocycloalkyl or substituted heterocycloalkyl; n has a value from 0 to 4; m has a value from 0 to 6; D represents S or O; R ² represents halogen or H; R ³ represents H; and R ⁴ is optionally substituted pyrazole, optionally substituted pyridyl, optionally substituted pyridinone or optionally substituted pyridine-N-oxide.