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 composition comprising a compound of formula (I-b):
or a pharmaceutically acceptable salt thereof 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, halo, NR 10 R 11 , C 1-6 alkoxy, C 1-6 fluoroalkyl 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, NR 10 R 11 , C 1-6 alkoxy, C 1-6 fluoroalkyl or C 1-6 alkyl; and
R 10 and R 11 are independently hydrogen, C 1-6 alkyl or trialkyl silyl;
and an anti-cancer agent,
wherein said composition is optionally in association with one or more pharmaceutical carriers, excipients, auxiliaries and/or diluents.
2 . The composition of claim 1 , wherein the anti-cancer agent is cisplatin, dehydroequol or paclitaxel.
3 . The composition of claim 1 , wherein the compound of formula (I-b) is selected from compound Nos. 1 to 9 and 42 as set forth below:
4 . The composition of claim 2 , wherein the compound of formula (I-b) is:
5 . The composition of claim 3 , wherein the anti-cancer agent is dehydroequol.
6 . The composition of claim 4 , wherein the anti-cancer agent is dehydroequol.
7 . A method for the treatment, prevention or amelioration of cancer or a tumour mass, which comprises administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I-b) as defined in claim 1 .
8 . The method of claim 7 , wherein the compound of formula (I-b) is selected from compound Nos. 1 to 9 and 42.
9 . The method of claim 7 , wherein the cancer or tumour mass is of epithelial origin, of mesenchymal origin or of neural origin.
10 . The method of claim 9 , wherein the cancer or tumour mass of epithelial origin is prostate, ovarian, cervical, breast, gall-bladder, pancreatic, colorectal, renal or non-small lung cancer.
11 . The method of claim 9 , wherein the cancer or tumour mass of mesenchymal origin is melanoma, mesothelioma or sarcoma cancer.
12 . The method of claim 9 , wherein the cancer or tumour mass of neural origin is glioma.
13 . The method of claim 7 , wherein the compound is simultaneously administered with an anti-cancer agent.
14 . The method of claim 7 , wherein the compound is sequentially administered with an anti-cancer agent.
15 . The method of claim 13 , wherein the anti-cancer agent is cisplatin, dehydroequol or paclitaxel.
16 . The method of claim 14 , wherein the anti-cancer agent is cisplatin, dehydroequol or paclitaxel.
17 . The method of claim 13 , wherein the compound of formula (I-b) is:
said anti-cancer agent is dehydroequol, and said subject is afflicted with ovarian or pancreatic cancer.
18 . The method of claim 14 , wherein the compound of formula (I-b) is:
said anti-cancer agent is dehydroequol, and said subject is afflicted with ovarian or pancreatic cancer.
19 . The method of claim 7 , wherein the compound acts as a radiosensitising agent.
20 . The method of claim 7 , wherein the compound acts as a chemosensitising agent.