Polycyclic compounds possessing antitumor activity

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to novel polycyclic compounds of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7, cycle A, cycles B, X, Y and Z have values given in the invention claims and in description of the claim, and to their pharmaceutically acceptable salts also. Proposed compound possess an antitumor activity and can be used in treatment of oncological diseases. Also, invention relates to a pharmaceutical composition based on these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

23 cl, 1 tbl, 57 ex

 

The text descriptions are given in facsimile form.

1. Polycyclic compounds of the formula (I)

where cycle And means pyridine;

R1and R2independently mean hydrogen, halogen, C1-C5alkyl, amino, mono(C1-C5)alkylamino, di(C1-C5)alkylamino or-Y'-Z'-N(R6')(R7'), where

Y' is N(R9), where R9means hydrogen or C1-C5alkyl,

Z' means2-C5alkylen,

R6and R7independently mean hydrogen, C1-C5alkyl;

cycle means benzene, naphthalene cycle or benzene, substituted C1-C5alkylenedioxy;

R3, R4and R5independent means vador is d, halogen, hydroxy, mercapto, C1-C5alkyl, C1-C5halogenated,1-C5alkoxy, C1-C5halogenoalkane,3-C5alkenylacyl,1-C5alkylthio,1-C5alkylsulfonyl,1-C5alkylsulfonyl, amino, mono(C1-C5)alkylamino or di(C1-C5)alkylamino;

X is O or N-O-R8where R8means hydrogen, C1-C5alkyl or C3-C5alkenyl;

Y represents O, S or N(R9), where R9means hydrogen or C1-C5alkyl,

Z means With2-C4alkylene, optionally substituted radical (radicals)1-C5alkyl;

R6and R7independently mean hydrogen, C1-C5alkyl, optionally substituted by hydroxy group, or

R6and R7together with the adjacent nitrogen atom form a saturated cycle which may contain 3 to 6 carbon atoms and 1-2 heteroatoms selected from oxygen, nitrogen and/or sulfur, or R6forms videopreteen cycle together with the neighboring nitrogen nitrogen, and Z, or R6forms videopreteen cycle together with the adjacent nitrogen atom, N(R9and Z,

or their pharmaceutically acceptable salts.

2. Polycyclic compound according to claim 1, where the loop means In benzene.

3. Politicly the definition of the compounds according to claim 1, where one of R1and R2means hydrogen, C1-C5alkyl or-NHCH2C(CH3)2CH2N(CH3)2-.

4. Polycyclic compound according to claim 3, where one of R1and R2means hydrogen, -CH3or-NHCH2C(CH3)2CH2N(CH3)2.

5. Polycyclic compound according to claim 3, where one of R1and R2means hydrogen.

6. Polycyclic compound according to claim 3, where one of R1and R2means-CH3.

7. Polycyclic compound according to claim 3, where one of R1and R2means-NHCH2C(CH3)2CH2N(CH3)2.

8. Polycyclic compound according to claim 3, where R1means hydrogen, and R2means-CH3.

9. Polycyclic compound according to claim 3, where R1and R2mean hydrogen.

10. Polycyclic compound according to claim 1 where X is O, NOH or NOCH3.

11. Polycyclic compound of claim 10 where X is O.

12. Polycyclic compound of claim 10, where X means NOCH3.

13. Polycyclic compound of claim 10 where X is NOH.

14. Polycyclic compound according to claim 1, where-Y-Z-N(R6)(R7means-NHCH2CH2N(CH3)2or-NHCH2CH2(pyrrolidin-1-yl).

15. Polycyclic connection 14, where-Y-Z-N(R6)(R7means-NHCH2CH2 N(CH3)2.

16. Polycyclic connection 14, where-Y-Z-N(R6)(R7means-NHCH2CH2(pyrrolidin-1-yl).

17. Polycyclic compound according to claim 1, where R3, R4and R5mean

(a) all hydrogen

b) one means fluorine, and the other two denote hydrogen,

in one means hydroxy, and the other two denote hydrogen,

g) means och3and the other two denote hydrogen, or

d) one means hydrogen, the second means hydroxy, and the third means of CH3.

18. Polycyclic connection 17, where R3, R4and R5mean

(a) all hydrogen

b) R3, R4mean hydrogen, and R5means hydroxy,

in R3, R4mean hydrogen, and R5means och3or

g) R3means hydrogen, R4means methyl, and R5means hydroxy.

19. Polycyclic compound according to any one of claims 1 to 18, which is selected from the group including

a) 6-(2-diethylaminoethylamine)-3-methoxy-5,9-database[with]fluoren-7-he,

b) 6-(2-diethylaminoethylamine)-3-hydroxy-5,9-database[with]fluoren-7-he,

C) 6-(2-diethylaminoethylamine)-5,9-database[with]fluoren-7-he,

g) 6-(2-diethylaminoethylamine)-2-fluoro-3-methoxy-5,9-database[with]fluoren-7-he,

e) 6-(2-dimethylamino is ylamino)-3-hydroxy-4-methyl-5,9-diazepines[with]fluoren-7-he,

e) 6-(2-diethylaminoethylamine)-3-ethoxy-5,9-database[with]fluoren-7-he,

g) 3-allyloxy-6-(2-diethylaminoethylamine)-5,9-database[with]fluoren-7-he,

C) 3-chloro-6-(2-diethylaminoethylamine)-5,9-database[with]fluoren-7-he,

I) 6-(2-diethylaminoethylamine)-1,3-dimethoxy-5,9-database[with]fluoren-7-he,

K) 6-(2-diethylaminoethylamine)-5,9-diazinane[1,2-a]phenanthrene-7-he,

l) 6-(2-diethylaminoethylamine)-1,3-dioxa-5,9-diazinane[5,6-C]fluoren-7-he,

m) 6-(2-diethylaminoethylamine)-3-methoxy-5,10-database[with]fluoren-7-he,

h) 6-(2-diethylaminoethylamine)-3-hydroxy-5,10-database[with]fluoren-7-he,

o) 3-hydroxy-6-(2-pyrrolidin-1 ylethylamine)-5,10-database[with]fluoren-7-he,

p) 6-(2-diethylaminoethylamine)-3-hydroxy-4-methyl-5,10-database[with]fluoren-7-he,

R) 3-methoxy-4-methyl-6-(2-pyrrolidin-1 ylethylamine)-5,10-database[with]fluoren-7-he,

C) 3-hydroxy-4-methyl-6-(2-pyrrolidin-1 ylethylamine)-5,10-database[with]fluoren-7-he,

t) 3-methoxy-6-(2-pyrrolidin-1 ylethylamine)-5,9-database[with]fluoren-7-he,

I) 3-methoxy-6-(2-methylaminoethanol)-5,9-database[with]fluoren-7-he,

f) 3-methoxy-6-(4-methylpiperazin-1-yl)-5,9-database[with]fluoren-7-he,

x) 3-hydroxy-6-(2-pyrrolidin-1 ylethylamine)-5,9-database[with]fluoren-7-he,

C) 3-hydroxy-6-(2-morpholine-4-ylethylamine)-5,9-database[with]fluoren-7-about the,

h) 6-[(2-dimethylaminoethyl)methylamino]-3-hydroxy-5,9-database[with]fluoren-7-he,

W) 6-(2-dimethylaminoethoxy)-3-hydroxy-5,9-database[with]fluoren-7-he,

g) 6-(2-diethylaminoethylamine)-3-methoxy-9-methyl-5,10-database[with] fluoren-7-he,

e) 6,11-bis-(2-diethylaminoethylamine)-3-methoxy-5,10-database[with]fluoren-7-he,

Yu) 11-(3-dimethylamino-2,2-dimethylpropylene)-6-(2-diethylaminoethylamine)-3-methoxy-5,10-database[with] fluoren-7-he,

I) 11-(3-dimethylamino-2,2-dimethylpropylene)-6-(2-diethylaminoethylamine)-3-methoxy-4-methyl-5,10-database[with]fluoren-7-he,

AA) 6-(2-diethylaminoethylamine)-3-hydroxy-9-methyl-5,10-database[with]fluoren-7-he,

BB) 6-(2-diethylaminoethylamine)-3-hydroxy-8-methyl-5,9-database[with]fluoren-7-he,

BB) 11-(3-dimethylamino-2,2-dimethylpropylene)-6-(2-diethylaminoethylamine)-3-hydroxy-4-methyl-5,10-database[with]fluoren-7-he,

yy) oxime 6-(2-diethylaminoethylamine)-3-hydroxy-5,9-database[with]fluoren-7-it,

DD) 0-methyloxime 6-(2-diethylaminoethylamine)-3-hydroxy-5,9-database[with]fluoren-7-she

it) O-methyloxime 6-(2-diethylaminoethylamine)-3-hydroxy-4-methyl-5,9-database[with]fluoren-7-it.

20. Polycyclic compound according to claim 19, which is selected from the group including

a) 6-(2-diethylaminoethylamine)-3-methoxy-5,9-database[with]fluoren-7-he,

b) 6-(2-dimethylene is etileno)-3-hydroxy-5,9-database[with]fluoren-7-he,

C) 6-(2-diethylaminoethylamine)-5,9-database[with]fluoren-7-he,

g) 6-(2-diethylaminoethylamine)-3-hydroxy-5,10-database[with]fluoren-7-he,

d) 3-hydroxy-6-(2-pyrrolidin-1 ylethylamine)-5,10-database[with]fluoren-7-he,

e) 6-(2-diethylaminoethylamine)-3-hydroxy-4-methyl-5,10-database[with]fluoren-7-he,

g) 3-hydroxy-4-methyl-6-(2-pyrrolidin-1 ylethylamine)-5,10-database[with]fluoren-7-he,

C) 3-hydroxy-6-(2-pyrrolidin-1 ylethylamine)-5,9-database[with]fluoren-7-he,

I) 6-(2-diethylaminoethylamine)-3-hydroxy-9-methyl-5,10-database[with]fluoren-7-he

K) 11-(3-dimethylamino-2,2-dimethylpropylene)-6-(2-diethylaminoethylamine)-3-hydroxy-4-methyl-5,10-database[with]fluoren-7-he.

21. Pharmaceutical composition having antitumor activity, comprising as an active ingredient polycyclic compound according to any one of claims 1 to 19 and a pharmaceutically acceptable carrier.

22. The pharmaceutical composition according to item 21, which is suitable for oral or parenteral administration.



 

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EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

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22 cl, 1 tbl, 4 ex

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EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

20 cl, 1 tbl, 20 ex

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