US 6,583,138 B1 · Heterocyclic-ring condensed benzothiazine compound

Abstract

The invention provides a novel heterocyclic ring condensed benzothiazine compound which is effective for prevention or remedy of disease, in which histamine, leukotriene and the like participate. The heterocyclic ring condensed benzothiazine compound of the present invention or a pharmacologically acceptable salt thereof is effective for prevention or remedy of disease, in which a chemical mediator, such as histamine, leukotriene and the like, participate, for example, asthma, allergic coryza, atopic dermatitis, hives, hay fever, gastrointestinal allergy, food allergy and the like. Further, the heterocyclic ring condensed benzothiazine compound of the present invention, its pharmacologically acceptable salt or hydrates thereof is represented by the following formula: In the formula, the ring Het represents an unsaturated heterocyclic ring; R1 and R2 are the same as or different from each other, and each represents halogen atom, a lower alkyl group that may be substituted with a halogen atom, a lower alkoxy group that may be substituted with a halogen atom, a lower alkyl lower alkoxy group, cyano group; D represents a lower alkylene group and the like that may have a substituent; Q represents, for example, the formula —NR20R2 (in the formula, R20 and R21 are the same as or different from each other, and each represents hydrogen atom, a lower alkyl group that may be substituted with a halogen atom, an aryl group that may have a substituent, an arylalkyl group that may have a substituent, a heteroaryl group that may have a substituent or a heteroarylalkyl group that may have a substituent, or R20 and R21 may form a 3- to 8-membered ring along with the nitrogen atom to which they are bound); and x represents an integer of from 1 to 2.

A compound represented by the formula (I), or a pharmacologically acceptable salt or hydrate thereof

wherein
Het represents thiophene, thiazole, furan, pyridine, pyrimidine, pyrazine, pyrizadine, quinoline, isoquinoline or naphthyridine that may be substituted with from 1 to 3 substituents independently selected from the group defined by Z,
wherein each Z is independently selected from the group consisting of a hydroxyl group, a lower alkyl group, a lower alkoxy group, a halogen atom, a cyano group, an acyl group, an amino group, a nitro group, a carboxyl group that may have a protective group, a carbamoyl group, an acylamino group, a sulfamoyl group, an alkylsulfonylamino group, an arylsulfonylamino group, a carboxyalkyl group, a carboxylalkoxy group, a methylenedioxy group, and an ethylenedioxy group;
R1 and R2 are the same as or different from each other, and each represents
(1) a halogen atom,
(2) a lower alkyl group that may be substituted with 1 to 3 halogen atoms,
(3) a lower alkoxy group that may be substituted with 1 to 3 halogen atoms,
(4) a lower alkoxy lower alkyl group,
(5) a cyano group,
(6) a carbamoyl group that may have 1 or 2 substituents on the nitrogen atom thereof, wherein said substituents are independently selected from the group defined by Z above, or
(7) a carboxyl group that may have a protective group, wherein
R1 and R2 may form a ring along with the carbon atoms to which they are bound, which ring may contain an oxygen atom, a sulfur atom or a nitrogen atom;
D represents a lower alkylene chain, a lower alkenylene chain, a lower alkynylene chain, or
wherein
m and 1 each represents an integer of from 0 to 6, and ring A represents a hydrocarbon ring;
Q represents
(1) a carbamoyl group that may have 1 or 2 substituents on the nitrogen atom thereof, wherein said substituents are independently selected from the group defined by Z above,
(2) an acyl group,
(3) an acyl lower alkyl group,
(4) a carboxyl group that may have a protective group, or
(5) the formula —NR20R21, wherein
R20 and R21 are the same as or different from each other, and each represents
(a) a hydrogen atom,
(b) a lower alkyl group that may be substituted with a halogen atom,
(c) a lower alkoxy group that may be substituted with 1 to 3 halogen atoms,
(d) a lower alkyl group that is substituted with a hydroxyl group,
(e) a lower alkoxy lower alkyl group,
(f) an aryl group that may have a substituent selected from the group defined by Z above,
(g) an aryl lower alkyl group that may have a substituent selected from the group defined by Z above,
(h) a monocyclic or condensed ring heteroaryl group containing from 1 to 4 of at least one selected from the group consisting of a sulfur atom, an oxygen atom and a nitrogen atom, which heteroaryl group may have a substituent selected from the group defined by Z above,
(i) a monocyclic or condensed ring heteroaryl lower alkyl group containing from 1 to 4 of at least one selected from the group consisting of a sulfur atom, an oxygen atom and a nitrogen atom, which heteroaryl lower alkyl group may have a substituent selected from the group defined by Z above,
(j) an aryloxy group,
(k) an aryl lower alkoxy group that may have a substituent selected from the group defined by Z above,
(l) a heteroaryloxy group that may have a substituent selected from the group defined by Z above,
(m) a heteroaryl lower alkoxy group that may have a substituent selected from the group defined by Z above,
(n) a carboxyalkyl group that may have a protective group,
(o) an acyl group,
(p) an acyl lower alkyl group,
(q) an acylamino group,
(r) an acylamino lower alkyl group,
(s) a carbamoyl lower alkyl group that may have a substituent selected from the group defined by Z above,
(t) an amino lower alkyl group,
(u) a cyano lower alkyl group,
(v) an acyl lower alkyl group,
(w) a lower cycloalkyl group,
(x) a lower cycloalkyl lower alkyl group, or
(y) an amidino group that may be substituted with a lower alkyl group,
wherein R20 and R21 may form a 3- to 8-membered ring along with the nitrogen atom to which they are bound, and the ring may have, as a component constituting the ring, in addition to the carbon atoms, at least one selected from the group consisting of a nitrogen atom, a sulfur atom, an oxygen atom and the formula —NR22,
wherein R22 represents
(1) a hydrogen atom,
(2) a lower alkyl group that may be substituted with 1 to 3 halogen atoms,
(3) an acyl group,
(4) an acyl lower alkyl group,
(5) an aryl group that may have a substituent selected from the group defined by Z above,
(6) a monocyclic or condensed ring heteroaryl group containing from 1 to 4 of at least one selected from the group consisting of a sulfur atom, an oxygen atom and a nitrogen atom, which heteroaryl group may have a substituent selected from the group defined by Z above,
(7) an arylalkyl group that may have a substituent selected from the group defined by Z above,
(8) a monocyclic or condensed ring heteroarylalkyl group containing 1 to 4 of at least one selected from the group consisting of a sulfur atom, an oxygen atom and a nitrogen atom, which heteroarylalkyl group may have a substituent selected from the group defined by Z above, or
(9) the formula —S(O)s—(Y)u—R23, wherein
R23 represents
(a) a hydrogen atom,
(b) a lower alkyl group that may be substituted with 1 to 3 halogen atoms, or
(c) an aryl group that may have a substituent selected from the group defined by Z above,
Y represents a methylene chain,
s represents an integer of from 0 to 2, and
u represents 0 or 1;
and
x represents an integer of from 0 to 2.

64 more elements

Heterocyclic-ring condensed benzothiazine compound

Life of this patent

Heterocyclic-ring condensed benzothiazine compound

Life of this patent

Abstract

Claims31