Phenylazole compounds production process and antioxidants
The present invention is directed to compounds represented by the formula (1): B-D-Z (1), wherein B represent the following formula (B-1), (B-2) or (B-3); A represents an optionally substituted imidazole or pyrazole group; E represents the following formula (1a); X represents an oxygen atom, the formula: SOu, or the formula: N—R 9 ; Y represents a carbon atom or a nitrogen atom; D represents an oxygen atom, a sulfur atom or the formula (1a); Z represents (a chroman-2-yl group, a chroman-4-yl group, a 2,3-dihydrobenzofuran-2-yl group, a 2,3-dihydrobenzofuran-3-yl group, etc.) which is substituted with NHR 10 or OR 11 )] or pharmaceutically acceptable salts thereof, and to antioxidants, therapeutic agents for kidney diseases or cerebrovascular disorder, and retinal oxidative damage inhibitors, which include the compounds as the active ingredient.
1. A compound represented by the formula (1):
B-D-Z (1)
[wherein B represents the following formula(B-1):
A represents an imidazolyl or pyrazolyl group represented by the following formula (A-1), (A-2), (A-3) or (A-4):
(wherein R 4 and R 5 each independently represents a C 1-6 alkyl group which may be substituted with G1, a C 1-6 alkoxy group which may be substituted with G1, a C 1-6 alkylsulfonyl group which may be substituted with G1, or a halogen atom; R 6 represents a hydrogen atom, a C 1-6 alkyl group which may be substituted with G1, a C 1-6 alkylcarbonyl group which may be substituted with G1, or a benzoyl group which may be substituted with G1, or a tetrahydropyranyl group;
G1 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6 alkoxy group, an amino group, a monomethylainino group, a dimethylamino group or a halogen atom,
s represents 0 or an integer of 1 to 3,
t represents 0 or an integer of 1 or 2, and
R 4 (s) or R 5 (s) may be the same or different when s or t is 2 or more);
R 1 represents a halogen atom, a nitro group, a cyano group, a hydroxyl group, a C 1-6 alkyl group which may be substituted with G2, a C 1-6 alkoxy group which may be substituted with G2, a C 1-6 alkylthio group which may be substituted with G2, a C 1-6 alkylcarbonyl group which may be substituted with G 2 , an amino group (which may be substituted with one or two C 1-6 alkyl groups), a benzoyl group which may be substituted with G2, or a benzyl group which may be substituted with G2;
R 2 represents a C 1-6 alkyl group which may be substituted with G2;
G2 represents a cyano group, a formyl group, a hydroxyl group, a C 6 alkoxy group, a C 1-6 alkoxycarbonyl group, a nitro group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom;
m represents 0 or an integer of 1 to 4, and R 1 (s) may be the same or different when m is 2 or more;
n represents 0 or an integer of 1 to 8, and R 2 (s) may be the same or different when n is 2 or more;
o represents an integer of 1;
in the formula (B-1), the dotted line represents a single bond or a double bond and does not simultaneously represent a double bond;
Y represents a carbon atom or a nitrogen atom, which may have a substituent selected from the group consisting of a hydrogen and a hydroxyl or a multiple bond that satisfies a valence;
E represents an oxygen atom, a sulfur atom or the following formula (1a) when Y represents a carbon atom;
(wherein R 60 represents a hydrogen atom, a C 1-6 alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6 alkoxy group, or a C 1-6 alkyl group); R 7 and R 8 each independently represents a hydrogen atom, a cyano group, a hydroxyl group, a halogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a C 1-6 acyloxy group, a C 3-6 cycloalkyl group which may be substituted with G2, or a phenyl group which may be substituted with G2;
j and k independently represent 0 or an integer of 1;
l represents 0 or an integer of 1 to 16;
R 7 (s) and R 8 (s) may be the same or different when 1 is 2 or more);
E represents the formula (1a) when Y represents a nitrogen atom;
D represents the formula (1a);
Z represents a 2,3-dihydrobenzofuran-2-yl group which is substituted with G3, or a 2,3-dihydrobenzofuran-3-yl group which is substituted with G3;
G3 represents the formula: NHR 10
{wherein R 10 represents a hydrogen atom, a C 1-6 alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6 alkoxy group, or a C 1-6 alkyl group)};
or the formula: OR 11
{wherein R 11 represents a hydrogen atom, a C 1-6 alkylcarbonyl group, or a benzoyl group (which may be substituted with a hydroxyl group, a C 1-6 alkoxy group, a halogen atom, or a C 1-6 alkyl group)}]
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein Z represents a group represented by the following formula (Z-2) or (Z-5):
[wherein * represents an asymmetric carbon atom; X 1 represents an oxygen atom; R 16 to R 19 and R 28 to R 32 each independently represents a hydrogen atom or a C 1-6 alkyl group, and
G3 represents the formula: NHR 10
{wherein R 10 represents a hydrogen atom, a C 1-6 alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6 alkoxy group, or a C 1-6 alkyl group)};
or the formula: OR 11
{wherein R 11 represents a hydrogen atom, a C 1-6 alkylcarbonyl group, or a benzoyl group (which may be substituted with a hydroxyl group, a C 1-6 alkoxy group, a halogen atom, or a C 1-6 alkyl group)}]
or a pharmaceutically acceptable salt thereof.
3. A pharmaceutical composition comprising one or more compounds or pharmaceutically acceptable salts thereof according to claim 1 or 2 and an excipient.