US 7,842,701 B2 · Pyrazoloquinolone derivative and use thereof

Abstract

The present invention provides a pyarzoloquinolone derivative having kinase inhibitory activity. The derivative is represented by the formula: wherein R1 is an aryl group which may be substituted, or an aromatic heterocyclic group which may be substituted; R2 is a hydrogen atom, an amino group which may be substituted, a hydroxy group which may be substituted, or a thiol group which may be substituted; R3, R4, R5 and R6, which may be identical or different, are each (1) a hydrogen atom, (2) a nitro group, (3) a cyano group, (4) a halogen atom, (5) a hydrocarbon group which may be substituted, (6) an amino group which may be substituted, (7) a hydroxy group which may be substituted, or (8) a thiol group which may be substituted; and R3 and R4, R4 and R5, and R5 and R6 may respectively form a ring together with the adjacent carbon atom, or salt thereof.

A compound represented by the formula:

wherein R1 is:
(1) a C6-12 aryl group which may be substituted with 1 to 3 substituents selected from:
(a) a C1-6 alkyl group which may be substituted with 1 to 3 substituents selected from
(i) a halogen atom,
(ii) a hydroxy group, and
(iii) a 5- to 8-membered heterocyclic group which may be substituted with a substituent selected from a hydroxy group and a C1-6 alkyl group, and has 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom;
(b) a C1-6 alkoxy group which may be substituted with a substituent selected from
(i) a hydroxy group,
(ii) a C1-6 alkoxy group,
(iii) a carboxy group,
(iv) a C1-6 alkoxy-carbonyl group,
(v) a carbamoyl group,
(vi) a carbamoyl group which is mono- or di-substituted with a C1-6 alkyl group which may be substituted with a substituent selected from a hydroxy group and a C1-6 alkylsulfonyl group,
(vii) a cyano group, and
(viii) a 5- to 8-membered heterocyclic group having 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom;
(c) a halogen atom;
(d) a hydroxy group;
(e) an amino group;
(f) a nitro group;
(g) a carboxy group;
(h) a C1-6 alkoxy-carbonyl group;
(i) a C1-6 alkyl-carbonyloxy group;
(j) a C6-12 aryloxy group which may be substituted with a substituent selected from a halogen atom, a hydroxy group and a C1-6 alkoxy group;
(k) a C6-14 aralkyloxy group;
(l) a C3-7 cycloalkyloxy group;
(m) a 5- to 8-membered heterocyclic-oxy group which may be substituted with a C1-6 alkyl group, and has 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom;
(n) a C1-6 alkylsulfonyl group;
and
(o) a C6-12 arylsulfonyl group, or
(2) a 5- or 6-membered aromatic heterocyclic group which may be substituted with 1 to 3 substituents selected from:
(a) a C1-6 alkyl group, and
(b) a C1-6 alkoxy group,
and has 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, or a group resulting from condensation of the 5- or 6-membered aromatic heterocyclic group with a benzene ring;
R2 is:
(1) a hydrogen atom, or
(2) an amino group which may be mono- or di-substituted with a C1-6 alkyl group;
R3 is a hydrogen atom;
R4 is:
(1) an amino group,
(2) a hydroxy group, or
(3) a group represented by the formula:
—X″(CH2)b″—R11″
wherein X″ is —O—, —NHSO2—, —NHCO— or —NR12″— (wherein R12″ is a hydrogen atom, or a C1-6 alkyl group which may be substituted with a 5- to 8-membered heterocyclic group having 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom),
b″ is an integer from 1 to 4, and
R11″ is a 5- to 8-membered heterocyclic group which may be substituted with a substituent selected from
(a) a hydroxy group, and
(b) a C1-6 alkyl group,
and has 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom;
R5 is:
(1) a hydrogen atom,
(2) a C1-6 alkoxy group, or
(3) a group represented by the formula:
—O—(CH2)b′″—R11′″
wherein b′″ is an integer from 2 to 4, and
R11′″ is a 5- to 8-membered heterocyclic group which may be substituted with a substituent selected from
(a) a C1-6 alkyl group, and
(b) a C6-14 aryl group which may be substituted with a halogen atom, and has 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom;
R6 is:
(1) a hydrogen atom,
(2) a hydroxy group,
(3) a C1-6 alkoxy group which may be substituted with a substituent selected from:
(a) a hydroxy group,
(b) a C1-6 alkoxy group,
(c) a carboxy group,
(d) a C1-6 alkoxy-carbonyl group,
(e) a carbamoyl group,
(f) a carbamoyl group which is mono- or di-substituted with a C1-6 alkyl group which may be substituted with an amino group which may be mono- or di-substituted with a C1-6 alkyl group,
(g) a carbamoyl group which is mono- or di-substituted with a 5- to 8-membered heterocyclic group having 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and
(h) a 5- to 8-membered heterocyclic-carbonyl group which may be substituted with a C1-6 alkyl group, and has 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom,
(4) a C7-14 aralkyloxy group, or
(5) a group represented by the formula:
—O—(CH2)b″″—R11″″
wherein b″″ is an integer from 1 to 4, and
R11″″ is a 5- to 8-membered heterocyclic group having 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom.

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Pyrazoloquinolone derivative and use thereof

Life of this patent

Pyrazoloquinolone derivative and use thereof

Life of this patent

Abstract

Claims4