RU2002103219A

RU2002103219A - Derivatives of mutilins and their use as antibacterial agents

Info

Publication number: RU2002103219A
Application number: RU2002103219/04A
Authority: RU
Inventors: Герд Ашер; Хайнц БЕРНЕР; Иоганнес ХИЛЬДЕБРАНДТ
Original assignee: Биохеми Гезельшафт М.Б.Х.
Priority date: 1999-07-30
Filing date: 2000-07-28
Publication date: 2003-09-20

Claims

1. The compound of the formula

in which R represents a hydrogen atom or alkyl;

R ₁ represents a group of the formula

wherein X is a sulfur or oxygen atom, NR ₁₀ where R ₁₀ is hydrogen or alkyl, or N ⁺ (R _'10) ₂ wherein R' ₁₀ is alkyl in the presence of an appropriate anion;

R ₉ is an amino group, alkyl, aryl, heterocyclyl or mercapto group, and if X is an oxygen atom, the additional value of R ₉ is a hydrogen atom;

R ₂ is phenylene;

R ₄ represents a hydrogen atom or alkyl;

R ₅ represents a hydrogen atom or alkyl;

R ₃ , R ' ₃ , R ₆ , R ₇ and R ₈ each independently from each other represents a hydrogen atom or deuterium;

or R and R ₂ together with the nitrogen atom to which they are attached form a non-aromatic heterocycle, and R ₁ represents a group of the formula

in which X and R ₉ have the meanings indicated above.

2. The compound of formula I according to claim 1, in which R represents a hydrogen atom; R ₁ represents a group of the formula

R ₉ represents an amino group, an alkyl, heterocyclyl or mercapto group,

and if X represents an oxygen atom, the additional value of R ₉ is a hydrogen atom;

R ₂ is phenylene; R ₄ represents a hydrogen atom or alkyl; R ₅ represents a hydrogen atom; R ₃ and R ′ ₃ are hydrogen atoms; R ₆ , R ₇ and R ₈ are hydrogen or deuterium atoms; or R and R ₂ together with the nitrogen atom to which they are attached form a non-aromatic heterocycle, and R ₁ represents a group of the formula

in which X represents an oxygen atom;

R ₉ is alkyl.

3. The compound according to claim 1, which corresponds to the formula

in which R _1S , denotes a group of the formula

in which R _6S represents a hydrogen atom or deuterium;

R _2S represents a hydrogen atom, methyl or tert-butyl;

R _7S represents a hydrogen atom or methyl;

R _3S , R _4S and R _5S are hydrogen or deuterium atoms.

4. The compound according to claim 1, which corresponds to the formula

in which R _3SS , R _4SS and R _5SS are hydrogen or deuterium atoms.

5. The compound according to claim 1, which is selected from the range including

14-O- (3- (piperidin-2-ylcarbonylamino) phenylsulfanylacetyl) mutiline;

14-O- (3- (piperidin-2-ylcarbonylamino) phenylsulfanylacetyl) -2,2,4-trideuteromutiline;

14-O- (3- (piperidin-2-ylcarbonylamino) -2,5-dimethylphenylthiomethylcarbonyl) mutiline;

14-O- (3- (piperidin-2-ylcarbonylamino) -2,5-dimethylphenylthiomethylcarbonyl) -2,2,4-trideuteromutiline;

14-O- (3- (piperidin-2-ylcarbonylamino) -5-tert-butylphenylsulfanylacetyl) mutiline and

14-O- (3- (piperidin-2-ylcarbonylamino) -5-tert-butylphenylsulfanylacetyl) -2,2,4-trideuteromutiline.

6. The compound according to any one of claims 1 to 5 in the form of a salt or in the form of a salt and in the form of a solvate, or in the form of a solvate.

7. The compound according to any one of claims 1 to 6 for use as a pharmaceutical.

8. The compound according to claim 7 for use as an antimicrobial agent.

9. The compound of formula I for use in the preparation of a medicament for the treatment of microbial diseases.

10. The compound of formula I for use in the preparation of a medicament for the treatment of microbial diseases caused by bacteria, including penicillin or multidrug resistant strains, vancomycin-resistant strains and methicillin-resistant strains.

11. A method of treating diseases caused by microbes, which includes the introduction into the body of a subject in need of such treatment, an effective amount of a compound of formula I.

12. A pharmaceutical composition comprising a compound of formula I in free form or in the form of a pharmaceutically acceptable salt in combination with at least one pharmaceutically acceptable carrier or diluent.

13. The compound of formula I for use as a veterinary agent.

14. The compound of formula I for the preparation of a veterinary composition, which can be used as a veterinary medicine.