Tetrahydro-1H-pyrido [3,4-b]indole anti-estrogenic drugs
The present disclosure provides tetrahydro-1H-pyrido[3,4-b]indole compounds or a pharmaceutically acceptable salt, solvate, hydrate, prodrug, stereoisomer, tautomer, rotamer, N-oxide and/or substituted derivative or, optionally in a pharmaceutical composition, for the modulation of disorders mediated by estrogen, or other disorders as more fully described herein.
1. A method of preventing recurrence of a cancer in a patient comprising administering to the patient a compound of Formula I:
or a pharmaceutically acceptable salt thereof,
wherein X is —CH 2 —or —O—;
Y is
R 1 and R 2 are each hydrogen;
R 3 and R 4 are each independently selected from hydrogen and halo, and when one of R 3 or R 4 is halo, the other of R 3 or R 4 is hydrogen;
R 5 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 0 -C 4 (C 3 -C 6 cycloalkyl) or C 1 -C 6 heteroalkyl;
R 6 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 0 -C 4 (C 3 -C 6 cycloalkyl); and
R 7 and R 8 are each independently selected from hydrogen or C 1 -C 6 alkyl.
2. The method of claim 1 , wherein the cancer is selected from breast cancer, ovarian cancer, endometrial cancer, vaginal cancer, lung cancer, bone cancer, uterine cancer and endometriosis.
3. The method of claim 1 , wherein the compound is administered as an adjunctive therapy after or instead of chemotherapy, radiation, or surgery.
4. The method of claim 3 , wherein the compound is administered after surgery.
5. The method of claim 1 , wherein the compound is administered prior to surgery.
6. The method of claim 2 , wherein the cancer is breast cancer.
7. The method of claim 6 , wherein the breast cancer has progressed in the presence of endocrine or aromatase therapy.
8. The method of claim 1 , wherein X is —O—.
9. The method of claim 1 , wherein Y is
10. The method of claim 1 , wherein Y is
11. The method of claim 1 , wherein R 5 is C 1 -C 6 [[ ]]alkyl or C 1 -C 6 [[ ]]haloalkyl.
12. The method of claim 1 , wherein R 7 and R 8 are each independently selected from hydrogen or C 1 -C 6 alkyl.
13. The method of claim 1 , wherein the compound is of Formula I(a):
or a pharmaceutically acceptable salt thereof.
14. The method of claim 13 , wherein R 1 , R 2 , R 3 and R 4 are each hydrogen.
15. The method of claim 1 , wherein the compound is of Formula I(c):
or a pharmaceutically acceptable salt thereof.
16. The method of claim 15 , wherein R 1 , R 2 , R 3 and R 4 are each hydrogen.
17. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
18. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
19. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.