Chroman derivatives, medicaments and use in therapy
Novel 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 general formula (I) or a pharmaceutically acceptable salt thereof:
wherein
R 1 is hydrogen;
R 2 and R 3 are independently hydrogen, hydroxy, alkoxy, alkyl, cycloalkyl, halo or OC(O)R 7 , with the exception that R 2 and R 3 are not both hydrogen;
R 4 , R 5 and R 6 are independently hydrogen, hydroxy, or alkoxy;
R 7 is hydrogen, alkyl, cycloalkyl, aryl, arylalkyl or amino; and
R 9 is hydrogen, hydroxy, alkyl, alkoxy, cycloalkyl or halo.
2. A compound of general formula (I-a) or a pharmaceutically acceptable salt thereof:
wherein
R 1 is hydrogen;
R 2 and R 3 are independently hydrogen, hydroxy, alkoxy, halo or OC(O)R 7 , with the exception that R 2 and R 3 are not both hydrogen;
R 4 , R 5 and R 6 are independently hydrogen, hydroxy, or alkoxy; and
R 7 is hydrogen, alkyl, cycloalkyl, aryl, arylalkyl or amino.
3. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen;
R 2 and R 3 are independently hydrogen, hydroxy, C 1-4 -alkoxy, halo or OC(O)R 7 , provided that R 2 and R 3 are not both hydrogen;
R 4 , R 5 and R 6 are independently hydrogen, hydroxy, or alkoxy; and
R 7 is C 1-4 -alkyl, phenyl or benzyl.
4. The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen;
R 2 and R 3 are independently hydrogen, hydroxy, methoxy, ethoxy, propoxy, isopropoxy, bromo, chloro, fluoro or acetyloxy, with the exception that R 2 and R 3 are not both hydrogen;
R 4 is hydrogen, hydroxy, methoxy, ethoxy, propoxy, or isopropoxy; and
R 5 and R 6 are independently hydrogen, hydroxy, methoxy, ethoxy, propoxy, or isopropoxy.
5. The compound of claim 4 or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen;
R 2 and R 3 are independently hydrogen, hydroxy, methoxy, bromo or acetyloxy, with the exception that R 2 and R 3 are not both hydrogen;
R 4 and R 6 are independently hydrogen, hydroxy, or methoxy; and
R 5 is hydrogen.
6. A compound selected from the group consisting of:
3-(4-hydroxyphenyl)-4-(4-methoxyphenyl)chroman-7-ol;
3-(4-hydroxyphenyl)-4-phenylchroman-7-ol;
3-(4-hydroxyphenyl)-4-(3-methoxyphenyl)chroman-7-ol;
3-(3,4-dimethoxyphenyl)-4-(4-methoxyphenyl)chroman-7-ol;
3-(4-hydroxyphenyl)-4-(2,6-dimethoxy-4-hydroxyphenyl)chroman-7-ol;
3-(4-hydroxyphenyl)-4-(2-hydroxyphenyl)chroman-7-ol;
3-(3-hydroxyphenyl)-4-(3-methoxyphenyl)chroman-7-ol;
3-(4-hydroxyphenyl)-4-(4-hydroxyphenyl)chroman-7-ol;
3-(4-bromophenyl)-4-(4-methoxyphenyl)chroman-7-ol; and
3-(4-hydroxyphenyl)-4-(3-methoxyphenyl)chroman-7-ol.
7. The compound according to claim 6 , wherein said compound is selected from the group consisting of:
3-(4-hydroxyphenyl)-4-(4-methoxyphenyl)chroman-7-ol ; and
3-(4-hydroxyphenyl)-4-(4-hydroxyphenyl)chroman-7-ol.
8. A pharmaceutical composition which comprises one or more compounds of formula (I) or (I-a) of claims 1 or 2 , respectively, or a pharmaceutically acceptable salt thereof, in association with one or more pharmaceutical carriers, excipients, auxiliaries and/or diluents.
9. The pharmaceutical composition according to claim 8 , where said composition further comprises an additional chemotherapeutic agent.