RU98104414A

RU98104414A - NEW DERIVATIVES OF BENZOXASINDIONE, METHOD FOR PRODUCING AND USING THEM

Info

Publication number: RU98104414A
Application number: RU98104414/04A
Authority: RU
Inventors: Хайниш Лотар; Виттманн Штеффен; Мельманн Утэ; Райссбродт Рольф
Original assignee: Грюненталь Гмбх
Priority date: 1997-03-05
Filing date: 1998-03-04
Publication date: 2000-01-10

Claims

1. Derivatives of benzoxazinedione of the formula I

in which R ¹ represents H, COalkyl or COOalkyl, R ² represents H, alkyl, halogen, and R ³ represents the following substituents:
a) R ³ means -Z-CHR ⁴ -COR ⁵ , where Z represents a group

R ⁴ is H, alkyl, phenyl or substituted phenyl, especially hydroxy or acyloxyphenyl, or R ⁴ is (CH ₂ ) _n COX, where X is OA, where A is H, alkyl, an alkali metal ion or an ammonium ion, suitably substituted ammonium ion, or where X is the remainder of the active substance, especially the antibiotic residue linked through an OH or NH group, and where n is 1-10, or R ⁴ is (CH ₂ ) _n -Y, where Y represents a benzoxazinedione radical of the formula

where R ¹ and R ² have the above meanings, and both benzoxazinedione radicals may be identical or different, and n may mean 1-10, and R ⁵ means OA, where A has the above meanings, or R ⁵ represents the remainder of the active substance first of all, the antibiotic residue linked through an OH or NH group, or R ⁵ is NH-CHR ⁸ -COR ⁹ , where R ⁸ is H, alkyl, phenyl or substituted phenyl, and R ⁹ is OA, where A has the above values, or R ⁹ represents the remainder of the active substance, especially the remainder of the antibiotic, is bound through OH or an NH group, or R ⁵ represents a group

(the same group is R ¹⁷ ) where X and Y are as defined above, n is 1-10 and R ⁶ is H, alkyl, halogen, and R ⁷ is H, acyl, and n is 1-10 and m is 1-2, or
b) R ³ means CHR ⁴ -COR ⁵ , where R ⁴ and R ⁵ have the above meanings, or
C) R ³ represents a group

(the same group is R ¹⁸ )
where R ¹⁰ and / or R ¹¹ mean H, alkyl, phenyl or substituted phenyl, n means 1-10, a COR ⁹ and R ¹² can be in all possible positions, R ⁹ has the above meanings, a R ¹² represents H , alkyl, halogen, hydroxy, alkoxy, benzoxazinedione radical Y or R ¹² represents a group

(the same group is R ¹⁹ )
where R ¹ , R ² have the above meanings, R ¹⁴ , R ¹⁵ have the same meanings as R ¹ , R ² , an is 1-10, or
g) R ³ represents a group

(the same group is R ²⁰ ) where R ¹³ and COR ⁹ can be in all possible positions, a R ¹³ is H, alkyl, halogen, hydroxy, alkoxy or benzoxazinedione radical Y, and R ⁹ has the above meanings, and p is 0-2, or
d) R ³ represents a group

(the same group is R ²¹ ) or R ³ is a group

(the same group is R ²² ), where R ⁹ is as defined above and R ¹⁶ is H, alkyl, phenyl or substituted phenyl, or
e) R ³ represents the remainder of the active substance, first of all, the antibiotic residue bound via an OH or NH group, as well as physiologically resolved esters of such compounds of formula I having a free carboxyl group in the residue R ³ .

2. The compounds of formula I according to claim 1, wherein R ¹ is carboxyalkyl, R ² is H, R ³ is CHR ⁴ -COR ⁵ , R ⁴ is H, alkyl, phenyl or p-hydroxyphenyl and R ⁵ is OH.

3. The compounds of formula I according to claim 1, where R ¹ means carboxyalkyl, R ² means H, R ³ means CH ₂ CONHCHR ⁸ -COOH, where R ⁸ means H, alkyl, phenyl or substituted phenyl.

4. (8-methoxycarbonyloxy-2,4-dioxobenzoxazin-3-yl) acetic acid according to claim 1.

5. (8-Methoxycarbonyloxy-2,4-dioxobenzoxazin-3-yl) acetyl glycine according to claim 1.

6. The compounds of formula I according to claim 1, where X or R ³ or R ⁵ or R ⁹ represents the remainder of the antibacterial active substance.

7. The compounds of formula I according to claim 1, wherein X or R ³ or R ⁵ or R ⁹ is a residue of any cephalosporin linked through an NH or OH group.

8. The compounds of formula I according to claim 1, wherein X or R ³ or R ⁵ or R ⁹ is the remainder of any penicillin linked through an NH or OH group.

9. The compounds of formula I according to claim 1 or 8, where X or R ³ or R ⁵ or R ⁹ represents an ampicillin residue.

10. The compounds of formula I according to claim 1 or 8, wherein X or R ³ or R ⁵ or R ⁹ is an amoxicillin or O-acylamoxicillin residue.

11. The compounds of formula I according to claim 1, where X or R ³ or R ⁵ or R ⁹ represents the remainder of 6-aminopenicillanic acid.

12. The compounds of formula I according to claim 1, wherein X or R ³ or R ⁵ or R ⁹ is any tetracycline residue linked through an NH or OH group.

13. The compounds of formula I according to claim 1, wherein X or R ³ or R ⁵ or R ⁹ is the residue of any macrolide bonded through an NH or OH group.

14. The compounds of formula I according to claim 1, wherein X or R ³ or R ⁵ or R ⁹ is the residue of any quinolone linked through an NH or OH group.

15. The compounds of formula I according to claim 1, wherein X or R ³ or R ⁵ or R ⁹ is the residue of any carbapenem linked via an NH or OH group.

16. N- (8-methoxycarbonyloxy-2,4-dioxobenzoxazin-3-yl-acetyl) ampicillin according to claim 1, 8 or 9.

17. N- (8-methoxycarbonyloxy-2,4-dioxobenzoxazin-3-yl-acetyl) amoxicillin according to claim 1, 8 or 10.

18. The use of compounds of formula I according to any one of paragraphs. 1-17 as bacterial growth factors.

19. The use of compounds of formula I according to any one of paragraphs. 1-17, containing the remainder of the active substance for X or R ³ or R ⁵ or R ⁹ as therapeutic agents for bacterial infections.

20. The use of compounds of formula I according to any one of paragraphs. 1-17 as therapeutic agents for diseases caused by metabolic disorders involving iron.

21. Medicines containing in their composition one of the compounds of formula I according to any one of paragraphs. 1-17 in conjunction with conventional excipients.

22. The compounds of formula I according to any one of paragraphs. 1-17 for use as a medicine.