Claims
- 1. A compound of the formula: ##STR3## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.6 and R.sub.7 are independently H, OH, or (C.sub.1 -C.sub.8)alkoxy; R.sub.2 and R.sub.3 together are --OCH.sub.2 O--; or R.sub.6 and R.sub.7 together are --OCH.sub.2 O--;
- R.sub.4 is H or (C.sub.1 -C.sub.8)alkyl;
- R.sub.5 is absent;
- R.sub.8 is absent; and
- R.sub.9 is --CH.dbd.CH-- or --(CH.sub.2).sub.2 ;
- provided that R.sub.1 or R.sub.2 is H;
- or a pharmaceutically acceptable salt thereof.
- 2. The compound of claim 1 wherein R.sub.6 and R.sub.7 are --OCH.sub.3.
- 3. The compound of claim 2 wherein R.sub.4 is CH.sub.3.
- 4. The compound of claim 3 wherein R.sub.1 is H, R.sub.2 and R.sub.3 are --OCH.sub.3.
- 5. The compound of claim 3 wherein R.sub.1 is H, and R.sub.2 and R.sub.3 are --OCH.sub.2 O--.
- 6. The compound of claim 2 wherein R.sub.4 is H.
- 7. The compound of claim 6 wherein R.sub.1 is H, R.sub.2 and R.sub.3 are --OCH.sub.3.
- 8. The compound of claim 6 wherein R.sub.1 is H and R.sub.2 and R.sub.3 are --OCH.sub.2 O--.
- 9. The compound 8-methyl-3,4,10,11-tetramethoxydibenzo[a,g]quinolizinium acetosulfate; 8-methyl-3,4-methylenedioxy-10,11-dimethoxydibenzo[a,g]-quinolizinium acetosulfate; 5,6-dihydro-8-methyl-3,4,10,11-tetramethoxy-dibenzo[a,g]quinolizinium acetosulfate; 5,6-dihydro-8-methyl-3,4-methylenedioxy-10,11-dimethoxydibenzo[a,g]quinolizinium acetosulfate; 5,6-dihydro-3,4,10,11-tetramethoxydibenzo[a,g]quinolizinium chloride; 5,6-dihydro-3,4-methylenedioxy-10,11-dimethoxydibenzo[a,g]quinolizinium chloride; 3,4,10,11-tetramethoxy-dibenzo[a,g]quinolizinium chloride; or 3,4-methylenedioxy-10,11-dimethoxy-dibenzo[a,g]quinolizinium chloride; or a pharmaceutically acceptable salt thereof.
- 10. A compound of the formula: ##STR4## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.6 and R.sub.7 are independently H, OH, or (C.sub.1 -C.sub.8)alkoxy; R.sub.2 and R.sub.3 together are --OCH.sub.2 O--; or R.sub.6 and R.sub.7 together are --OCH.sub.2 O--;
- R.sub.4 is H or (C.sub.1 -C.sub.8)alkyl;
- R.sub.5 is absent;
- R.sub.8 is absent; and
- R.sub.9 is --CH.dbd.CH--;
- provided that R.sub.1 or R.sub.2 is H;
- or a pharmaceutically acceptable salt thereof.
- 11. A compound of the formula: ##STR5## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.6 and R.sub.7 are independently H, OH, or (C.sub.1 -C.sub.8)alkoxy; R.sub.2 and R.sub.3 together are --OCH.sub.2 O--; or R.sub.6 and R.sub.7 together are --OCH.sub.2 O--; or
- R.sub.4 is H or (C.sub.1 -C.sub.8)alkyl;
- R.sub.5 is absent;
- R.sub.8 is absent; and
- R.sub.9 is --(CH.sub.2).sub.2 --;
- provided that R.sub.1 or R.sub.2 is H;
- or a pharmaceutically acceptable salt thereof.
- 12. A therapeutic method to inhibit cancer cell growth comprising administering to a mammal afflicted with cancer an amount of a compound of the formula: ##STR6## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.6 and R.sub.7 are independently H, OH, or (C.sub.1 -C.sub.8)alkoxy; R.sub.2 and R.sub.3 together are --OCH.sub.2 O--; or R.sub.6 and R.sub.7 together are --OCH.sub.2 O--;
- R.sub.4 is H or (C.sub.1 -C.sub.8)alkyl;
- R.sub.5 is absent;
- R.sub.8 is absent; and
- R.sub.9 is --CH.dbd.CH-- or --(CH.sub.2).sub.2 ;
- provided that R.sub.1 or R.sub.2 is H;
- or a pharmaceutically acceptable salt thereof.
- 13. A pharmaceutical composition comprising an effective amount of a compound of the formula: ##STR7## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.6 and R.sub.7 are independently H, OH, or (C.sub.1 -C.sub.8)alkoxy; R.sub.2 and R.sub.3 together are --OCH.sub.2 O--; or R.sub.6 and R.sub.7 together are --OCH.sub.2 O--;
- R.sub.4 is H or (C.sub.1 -C.sub.8)alkyl;
- R.sub.5 is absent;
- R.sub.8 is absent; and
- R.sub.9 is --CH.dbd.CH-- or --(CH.sub.2).sub.2 ;
- provided that R.sub.1 or R.sub.2 is H;
- or a pharmaceutically acceptable salt thereof; in combination with a pharmaceutically acceptable carrier.
- 14. A therapeutic method to inhibit cancer cell growth comprising administering to a mammal afflictcd with cancer an amount of a compound of the formula: ##STR8## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.6 and R.sub.7 are independently H, OH, or (C.sub.1 -C.sub.8)alkoxy; R.sub.2 and R.sub.3 together are --OCH.sub.2 O--; or R.sub.6 and R.sub.7 together are --OCH.sub.2 O--;
- R.sub.4 is H or (C.sub.1 -C.sub.8)alkyl;
- R.sub.5 is absent;
- R.sub.8 is absent; and
- R.sub.9 is --CH.dbd.CH-- or --(CH.sub.2).sub.2 ; provided R.sub.1 or R.sub.2 is H; or a pharmaceutically acceptable salt thereof; wherein the cancer cell is located in the central nervous system.
- 15. A compound of the formula: ##STR9## wherein R.sub.1, R.sub.2, R.sub.6 and R.sub.7 are independently H, OH, or (C.sub.1 -C.sub.8)alkoxy; R.sub.2 and R.sub.3 together are --OCH.sub.2 O--; or R.sub.6 and R.sub.7 together are --OCH.sub.2 O--;
- R.sub.3 is OH, (C.sub.1 -C.sub.8)alkoxy, or R.sub.2 and R.sub.3 together are --OCH.sub.2 O--;
- R.sub.4 is H or (C.sub.1 -C.sub.8)alkyl;
- R.sub.5 is absent;
- R.sub.8 is absent; and
- R.sub.9 is --CH.dbd.CH-- or --(CH.sub.2).sub.2 ;
- provided that R.sub.1 or R.sub.2 is H;
- or a pharmaceutically acceptable salt thereof.
- 16. A compound of the formula: ##STR10## wherein R.sub.1 is H;
- R.sub.2, R.sub.3, and R.sub.7 are independently H, OH, or (C.sub.1 -C.sub.8)alkoxy; R.sub.2 and R.sub.3 together are --OCH.sub.2 O--; or R.sub.6 and R.sub.7 together are --OCH.sub.2 O--;
- R.sub.4 is H or (C.sub.1 -C.sub.8)alkyl;
- R.sub.5 is absent;
- R.sub.8 is absent; and
- R.sub.9 is --CH.dbd.CH-- or --(CH.sub.2).sub.2 ;
- or a pharmaceutically acceptable salt thereof.
- 17. A compound of the formula: ##STR11## wherein R.sub.1, R.sub.3, R.sub.6 and R.sub.7 are independently H, OH, or (C.sub.1 -C.sub.8)alkoxy; or R.sub.6 and R.sub.7 together are --OCH.sub.2 O--;
- R.sub.2 is H;
- R.sub.4 is H or (C.sub.1 -C.sub.8)alkyl;
- R.sub.5 is absent;
- R.sub.8 is absent; and
- R.sub.9 is --CH.dbd.CH-- or --(CH.sub.2).sub.2 ;
- or a pharmaceutically acceptable salt thereof.
- 18. A pharmaceutically acceptable salt comprising 8-methyl-3,4-methylenedioxy-10,11-dimethoxydibenzo[a,g]-quinolizinium; 5,6-dihydro-8-methyl-3,4-methylenedioxy-10,11-dimethoxydibenzo[a,g]quinolizinium; 5,6-dihydro-3,4-methylenedioxy-10,11-dimethoxydibenzo[a,g]quinolizinium; or 3,4-methylenedioxy-10,11-dimethoxydibenzo[a,g]quinolizinium; and a pharmaceutically acceptable counterion.
- 19. A pharmaceutically acceptable salt of claim 18 comprising 8-methyl-3,4-methylenedioxy-10,11-dimethoxydibenzo[a,g]-quinolizinium and a pharmaceutically acceptable counterion.
- 20. A pharmaceutical composition comprising the salt of claim 19; and a pharmaceutically acceptable carrier.
- 21. A therapeutic method to inhibit cancer cell growth comprising administering to a mammal inflicted with cancer an effective amount of the salt of claim 19.
- 22. The method of claim 12 wherein the cancer is leukemia or melanoma.
- 23. The method of claim 12 wherein the cancer is a solid tumor.
- 24. The method of claim 12 wherein the cancer is a breast, lung, colon, or ovarian tumor.
CROSS-REFERENCE
This application in a 371 of PCT/US97/01676 filed Feb. 11, 1997 and claims priority of Provisional application Ser. No. 60/032,161 filed Oct. 1, 1996 and provisional application Ser. No. 60/011,452 filed Feb. 12, 1996.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US97/01676 |
2/11/1997 |
|
|
7/31/1998 |
7/31/1998 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/29106 |
8/14/1997 |
|
|
US Referenced Citations (12)
Foreign Referenced Citations (1)
Number |
Date |
Country |
0496634 |
Jul 1992 |
EPX |