Certain substituted polyketides, pharmaceutical compositions containing them and their use in treating tumors

1. A compound of formula I

where

A is

B is —CH 2 CH(OR 1 )—;

C is —C(R 4 )═C(R 4 )—;

D is —CH═C(R 4 )CH 2 —;

E is —CH(R 4 )CH═CHCH═CH 2 ;

F is —C(O)N(R 1 ) 2 ;

R 1 is H, (C 1-6 )alkyl, (C 1-6 )alkyl-Ar or Ar;

Ar is an aromatic or heteraromatic ring selected from

R 2 and R 3 are, independently, H, (C 1-6 )alkyl, OH, O(C 1-6 )alkyl, OCH 2 (CH 2 ) n OH, O(CH 2 ) n CO 2 H, OCH 2 (CH 2 ) n N(CH 3 ) 2 , OCH 2 (CH 2 ) n -4-morpholino, F, Cl, Br or CF 3 ;

R 4 is H or (C 1-6 )alkyl;

R 5 is (C 1-6 )alkyl, (C 1-6 )alkyl-Ar or Ar;

m is 0 or 1;

n is 1 or 2; and

q is 0-6,

or an acid or base addition salt thereof, where possible.

2. A compound according to claim 1 of formula Ia

where

A′ is

B′ is —CH 2 CH(OR 1′ )—;

C′ is —CH═CH—;

D′ is —CH═C(R 4′ )CH 2 —;

E′ is —CH(R 4′ )CH═CHCH═CH 2 ;

F′ is —C(O)N(R 1′ ) 2 ;

R 1′ is H, (C 1-3 )alkyl, (C 1-3 )alkyl-Ar′ or Ar′;

Ar′ is selected from

R 2 ′ and R 3 ′ are, independently, H, (C 1-6 )alkyl, OH, O(C 1-3 )alkyl, OCH 2 (CH 2 ) n OH, O(CH 2 ) n CO 2 H, OCH 2 (CH 2 ) n N(CH 3 ) 2 , OCH 2 (CH 2 ) n -4-morpholino, F, Cl, Br or CF 3 ;

R 4′ is H or (C 1-3 )alkyl;

R 5′ is (C 1-6 )alkyl, (C 1-3 )alkyl-Ar′ or Ar′;

m is 0 or 1; and

n is 1 or 2,

or an acid or base addition salt thereof, where possible.

3. A compound according to claim 2 of formula Ib

where

A″ is

B″ is —CH 2 CH(OR 1 —)—;

C″ is —CH═CH—;

D″ is —CH═C(R 4 —)CH 2 —;

E″ is —CH(R 4 —)CH═CHCH═CH 2 ;

R 1″ is H, (C 1-3 )alkyl, CH 2 — Ar″ or Ar″;

Ar″ is selected from

R 2 ″ and R 3 ″ are, independently, H, (C 1-6 )alkyl, OH, OCH 3 , OCH 2 CH 2 OH, OCH 2 CO 2 H, OCH 2 (CH 2 ) n N(CH 3 ) 2 , OCH 2 (CH 2 ) n -4-morpholino, F, Cl, Br or CF 3 ;

R 4″ is H or CH 3 ;

R 5″ is (C 1≢ )alkyl, —CH 2 —Ar″ or Ar″;

m is 0 or 1; and

n is 1 or 2,

or an acid or base addition salt thereof, where possible.

4. A compound according to claim 3 formula Ic

where

A′″ is

B′″ is —CH 2 CH(OR 1 —)—;

C′″ is —CH═CH—;

E′″ is —CH(R 4′″ ) CH═CHCH═CH 2 ;

R 1′″ is H, —CH 3 , CH 2 —Ar′″ or Ar′″;

Ar′″ is selected from

R 2 ′″ and R 3′″ are, independently, H, (C 1-4 )alkyl, OH, OCH 3 , OCH 2 CO 2 H, OCH 2 (CH 2 ) n N(CH 3 ) 2 , OCH 2 (CH 2 ) n -4-morpholino, F, Cl, Br or CF 3 ;

R 4″ is as defined above;

R 5′″ is (C 1-6 )alkyl, —CH 2 —Ar′″ or Ar′″;

m is 0 or 1; and

n is 1 or 2,

or an acid or base addition salt thereof, where possible.

5. A compound selected from

1 -cyclopentyl-5,7,9,11,13,15-hexamethyl-3,8,16,18-nonadecatetraene-2,6,12,14-tetrol-14-carbamate,

(2S,3Z,5S,6S,7S,8Z,11S,12R,13R,14S,15S,16Z) -1 -cyclopentyl-5,7,9,11,13,15-hexamethyl-3,8,16,18-nonadecatetraene-2,6,12,14-tetrol-1 4-carbamate,

or pharmaceutically acceptable acid or base addition salts thereof.

6. A compound according to claim 1 of formula I, or a pharmaceutically acceptable acid or base addition salt thereof, where possible.

7. A compound according to claim 2 of formula Ia, or a pharmaceutically acceptable acid or base addition salt thereof, where possible.

8. A compound according to claim 3 of formula Ib, or a pharmaceutically acceptable acid or base addition salt thereof, where possible.

9. A compound according to claim 4 of formula Ic, or a pharmaceutically acceptable acid or base addition salt thereof, where possible.

10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a therapeutically effective amount of a compound according to claim 6 , or a pharmaceutically acceptable acid or base addition salt thereof, where possible.

11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a therapeutically effective amount of a compound according to claim 7 , or a pharmaceutically acceptable acid or base addition salt thereof, where possible.

12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a therapeutically effective amount of a compound according to claim 8 , or a pharmaceutically acceptable acid or base addition salt thereof, where possible.

13. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a therapeutically effective amount of a compound according to claim 9 , or a pharmaceutically acceptable acid or base addition salt thereof, where possible.

14. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a therapeutically effective amount of a compound according to claim 5 , or a pharmaceutically acceptable acid or base addition salt thereof, where possible.