Claims
- 1. A 1,4-benzoxazine-2-acetic acid compound of the formula (I) ##STR19## wherein R.sup.1, R.sup.2 and R.sup.3 may be the same or different and each is a hydrogen atom, a lower alkyl, an alkoxy, a halogen atom or a hydroxy, R.sup.4 is a hydrogen atom, a halogen atom, a lower alkyl or an alkoxy, and R.sup.5 is an optionally esterified carboxyl, or a pharmaceutically acceptable salt thereof.
- 2. The 1,4-benzoxazine-2-acetic acid compound of claim 1, wherein R.sup.5 in the formula (I) is a carboxyl, or a pharmaceutically acceptable salt thereof.
- 3. The 1,4-benzoxazine-2-acetic acid compound of claim 1 or claim 2, wherein at least one of R.sup.1, R.sup.2 and R.sup.3 in the formula (I) is a halogen atom, or a pharmaceutically acceptable salt thereof.
- 4. The 1,4-benzoxazine-2-acetic acid compound of claim 3, wherein the halogen atom is a fluorine atom, or a pharmaceutically acceptable salt thereof.
- 5. The 1,4-benzoxazine-2-acetic acid compound of claim 1, which is a member selected from the group consisting of 2-[4-(5-chlorobenzothiazol-2-yl) methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[6-fluoro-4-(4, 5-difluorobenzothiazol-2-yl) methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[6-fluoro-4-(5,7-difluorobenzothiazol-2-yl) methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[4-(4,5-dichlorobenzothiazol-2-yl) methyl-6-fluoro-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[4-(4,5,7-trifluorobenzothiazol-2-yl) -methyl-3, 4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[4-(5,7-difluorobenzothiazol-2-yl) methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl ]acetic acid, 2-[4-(4,5-dichlorobenzothiazol-2-yl) methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[4-(4, 5,7-trifluorobenzothiazol-2-yl) methyl-6-methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[4-(4,5-difluorobenzothiazol-2-yl) methyl-6-methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[6-chloro-4-(4,5,7-trifluoro-benzothiazol-2-yl) methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[6-chloro-4-(4,5-difluorobenzothiazol-2-yl) methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[4-(5,7-difluorobenzothiazol-2-yl) methyl-7-methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, 2-[7-fluoro-4-(4,5,7-trifluorobenzothiazol-2-yl) methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid and 2-[7-fluoro-4-(4,5-difluorobenzothiazol-2-yl) methyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazin-2-yl]acetic acid, or a pharmaceutically acceptable salt thereof.
- 6. A method for producing 1,4-benzoxazine-2-acetic acid compound of claim 1 or a pharmaceutically acceptable salt thereof, comprising (a) reacting a compound of the formula (II) ##STR20## wherein R.sup.4 and R.sup.5 are as defined above, or a salt thereof, with a compound of the formula (III) ##STR21## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above, and Y is a halogen atom or --OSO.sub.2 R.sup.6 wherein R.sup.6 is lower alkyl, trifluoromethyl or optionally substituted phenyl, or
- (b) reacting a compound of the formula (IV) ##STR22## wherein R.sup.4 and R.sup.5 are as defined above, or a salt thereof, with a compound of the formula (V) ##STR23## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined above, or an acid addition salt thereof, followed by, on demand, hydrolysis of the compound obtained in the above (a) or (b).
- 7. A pharmaceutical composition comprising the 1,4-benzoxazine-2-acetic acid compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
- 8. The pharmaceutical composition of claim 7, which is an aldose reductase inhibitor.
- 9. The pharmaceutical composition of claim 7, which is an agent for the prevention or treatment of the complications of diabetes.
- 10. A method for inhibiting aldose reductase, comprising administering the 1,4-benzoxazine-2-acetic acid compound of claim 1 or a pharmaceutically acceptable salt thereof in an amount effective for inhibiting aldose reductase.
- 11. A method for preventing or treating the complications of diabetes, comprising administering the 1,4-benzoxazine-2-acetic acid compound of claim 1 or a pharmaceutically acceptable salt thereof in an amount effective for the prevention or treatment of the complications of diabetes.
Parent Case Info
This is a 35USC371 National Stage of International Application PCT/JP94/00005, filed Jan. 6, 1994.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/JP94/00005 |
1/6/1994 |
|
|
7/3/1996 |
7/3/1996 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO95/18805 |
7/13/1995 |
|
|
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4824833 |
Iijima et al. |
Apr 1989 |
|
4962200 |
Kihara et al. |
Oct 1990 |
|