Substituted chroman derivatives, medicaments and use in therapy
Novel substituted chroman derivatives and intermediate compounds, compositions containing same, methods for their preparation and uses thereof as therapeutic agents particularly as anti-cancer and chemotherapeutic selective agents are described.
1. A compound of the general formula (I-b):
wherein:
R 1 is hydroxy, halo, C 1-6 alkoxy or C 1-6 alkyl;
the drawing and R 2 together represent a double bond or
the drawing represents a single bond and R 2 is hydrogen or hydroxy;
R 3 , R 4 , and R 5 , are independently hydrogen, hydroxy, NR 10 R 11 , C 1-6 alkoxy or C 1-6 alkyl;
R 6 is hydrogen, hydroxy, halo, C 1-6 alkoxy or C 1-6 alkyl;
R 7 is hydroxy or C 1-6 alkoxy;
R 8 and R 9 are independently hydrogen, hydroxy, halo, C 1-6 alkoxy or C 1-6 alkyl; and
R 10 and R 11 are independently hydrogen, C 1-6 alkyl or trialkyl silyl;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein:
R 1 is methyl, methoxy or halo;
R 3 is hydrogen, hydroxy, methoxy or amino;
R 4 and R 5 are hydrogen;
R 6 is hydrogen;
R 7 is hydroxy or methoxy; and
R 8 and R 9 are independently hydrogen, hydroxy, halo, methoxy or methyl;
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 2 , wherein:
R 1 is methyl or bromo;
R 3 is methoxy and is in the 4″-position;
R 7 is hydroxy; and
R 8 is hydrogen and R 9 is hydrogen, hydroxy or methoxy, or
R 8 is hydroxy or methoxy and in the 3′-position and R 9 is hydrogen, or
R 8 and R 9 are both hydroxy or methoxy and R 8 is in the 3′-position;
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 3 , wherein:
the drawing represents a single bond; and
R 2 is hydrogen and cis to the hydrogen at C-3.
5. The compound of claim 1 , wherein R 1 is methyl.
6. The compound of claim 1 , wherein R 3 is methoxy or hydroxy.
7. The compound of claim 6 , wherein R 7 is hydroxy or C 1-6 alkoxy.
8. The compound of claim 7 , wherein R 7 is hydroxy or methoxy.
9. The compound of claim 1 , wherein R 8 and R 9 independently are hydrogen, hydroxy or C 1-6 alkoxy.
10. The compound of claim 9 , wherein R 8 and R 9 independently are hydrogen, hydroxy or methoxy.
11. The compound of claim 10 , wherein one of R 8 or R 9 is hydroxy or methoxy and the other of R 8 or R 9 is hydrogen.
12. The compound of claim 1 , wherein said compound is compound 1.1, 2.1 or 3.1
or a salt thereof.
13. The compound of claim 1 , wherein said compound is selected from compound Nos. 1 to 9 and 42, as set forth below:
14. The compound of claim 1 , wherein said compound is selected from compound Nos. 16-24, as set forth below:
15. The compound of claim 1 , wherein said compound is selected from compound Nos. 32-40, as set forth below:
16. A composition which comprises one or more compounds of formula (I-b) of claim 1 , or a pharmaceutically acceptable salt thereof, in association with one or more pharmaceutical carriers, excipients, auxiliaries and/or diluents.