RU2001126127A

RU2001126127A - Optically pure camptothecin analogues

Info

Publication number: RU2001126127A
Application number: RU2001126127/04A
Authority: RU
Inventors: Оливье ЛАВЕРНЬ; Денни Бигг; Кристоф ЛАНКО; Ален РОЛЛАН
Original assignee: Сосьете Де Консей Де Решерш Э Д'Аппликасьон Сьентифик (С.К.Р.А.С.)
Priority date: 1999-02-26
Filing date: 2000-02-24
Publication date: 2003-09-20

Claims

1. Compounds of General Formula (I _A )

where R ₁ means a lower alkyl radical;

R ₂ , R ₃ , R ₄ and R ₅ independently mean a hydrogen atom, a halide radical or a —OSO ₂ R ₁₀ radical;

R ₆ means a hydrogen atom; a linear or branched alkyl radical with 1-12 carbon atoms, possibly substituted by one or more, same or different halogen radicals; lower hydroxyalkyl, (lower alkoxy) - (lower alkyl), cycloalkyl, cycloalkyl (lower alkyl), nitro group, halogen atom, group - (CH ₂ ) _m SiR ₇ R ₈ R ₉ , substituted or unsubstituted aryl, or substituted or unsubstituted aryl (lower alkyl), wherein one or more substituents of the same or different aryl groups are selected from the radicals: lower alkyl, hydroxyl, halogen atom, amino group, (lower alkyl) amino group, di (lower alkyl) amino group, CF ₃ or OCF ₃ ;

R ₇ , R ₈ and R ₉ independently mean a lower alkyl radical;

R ₁₀ means a lower alkyl radical, possibly substituted by one or more, same or different halogen radicals, or an aryl radical, possibly substituted by one or more, same or different, lower alkyl radicals;

m is an integer from 0 to 6;

with the proviso that when the term “lower alkyl” refers to an alkyl radical, it includes at most 6 carbon atoms, and when R ₂ is H, then:

- R ₆ means a linear or branched alkyl radical with 7-12 carbon atoms, - (CH ₂ ) _m SiR ₇ R ₈ R ₉ or aryl substituted by one or more, same or different substituents selected from a di (lower alkyl) amino group or OCF ₃ and / or at least one of the radicals R ₃ , R ₄ or R ₅ means - OSO ₂ R ₁₀ ;

or addition salts of these compounds.

2. The compounds according to claim 1, in which R ₁ means an ethyl radical.

3. The compounds of formula (I _A ) according to claim 2, representing one of the following compounds:

(5R) -5-ethyl-8-fluoro-5-hydroxy-4,5,13,15-tetrahydro-1H, 3H-oxepino [3 ', 4': 6,7] indolisino [1,2-b] quinoline-3.15-dione;

(5R) -5-ethyl-9,10-difluoro-5-hydroxy-12- (2-trimethylsilylethyl) -4,5,13,15-tetrahydro-1H, 3H-oxepino [3 ', 4': 6, 7] indolisino [1,2-b] quinolin-3.15-dione;

(5R) -5-ethyl-5-hydroxy-12- (2-trimethylsilylethyl) -4,5,13,15-tetrahydro-1H, 3H-oxepino [3 ', 4': 6,7] indolisino [1, 2-b] quinolin-3.15-dione;

(5R) -12-decyl-5-ethyl-9-fluoro-5-hydroxy-4,5,13,15-tetrahydro-1H, 3H-oxepino [3 ', 4': 6,7] indolisino [1, 2-b] quinolin-3.15-dione;

(5R) -12-decyl-5-ethyl-9,10-difluoro-5-hydroxy-4,5,13,15-tetrahydro-1H, 3H-oxepino [3 ', 4': 6,7] indolisino [ 1,2-b] quinoline-3.15-dione;

(5R) -12-decyl-5-ethyl-9,11-difluoro-5-hydroxy-4,5,13,15-tetrahydro-1H, 3H-oxepino [3 ', 4': 6,7] indolisino [ 1,2-b] quinoline-3.15-dione;

(5R) -5-ethyl-9-fluoro-5-hydroxy-12- (4-trifluoromethoxyphenyl) -4,5,13,15-tetrahydro-1H, 3H-oxepino [3 ', 4': 6,7] indolisino [1,2-b] quinoline-3.15-dione;

(5R) -12- (4-dimethylaminophenyl) -5-ethyl-9-fluoro-5-hydroxy-4,5,13,15-tetrahydro-1H, 3H-oxepino [3 ', 4': 6,7] indolisino [1,2-b] quinoline-3.15-dione;

(5R) -5-ethyl-9-fluoro-5-hydroxy-3,15-dioxo-4,5,13,15-tetrahydro-1H, 3H-oxepino [3 ', 4': 6,7] indolisino [ 1,2-b] quinolin-10-yl trifluoromethanesulfonate.

4. The compounds of formula (I _A ) according to claim 3, representing one of the following compounds:

(5R) -5-ethyl-5-hydroxy-12- (2-trimethylsilylethyl) -4,5,13,15-tetrahydro-1H, 3H-oxepino [3 ', 4': 6,7] indolisino [1, 2-b] quinolin-3.15-dione.

5. The compound of formula (I _A ) according to any one of claims 1 to 4, or a pharmaceutically acceptable salt of the above compound, as a medicine.

6. A pharmaceutical composition containing, as an active principle, at least one compound according to any one of claims 1 to 4.

7. The use of a compound according to any one of claims 1 to 4 for the manufacture of a medicament for inhibiting topoisomerases and mainly topoisomerases of type I or type II.

8. The use of a compound according to any one of claims 1 to 4 for the manufacture of antitumor drugs.

9. The use of a compound according to any one of claims 1 to 4 for the preparation of antiviral drugs.

10. The use of a compound according to any one of claims 1 to 4 for the manufacture of antiparasitic drugs.