B-homoestra-1,3,5(10)-trienes as modulators of tubulin polymerization
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsErnest Hamel, Mark S. Cushman
Life of this patent
Estimating the term…
Abstract
The invention provides B-ring expanded estra-1,3,5(10)-triene compounds of general formula (1) which modulate the polymerization of tubulin and/or the depolymerization of microtubules. The compounds have anti-angiogenic and anti-tumor activity. The invention also provides methods of preparing the compounds, and methods of using the compounds for the treatment of cancer or other mammalian diseases characterized by undesirable angiogenesis. The compounds of the invention are also expected to have utility as research tools.
Claims39
A compound of formula
- wherein:
- A is selected from the group consisting of CH2, NR4, C═O, C═NOH, CHNHCR5 and CHOH;
- B is selected from the group consisting of CH2 and C═O;
- R1 is selected from the group consisting of H, methyl, ethyl, n-propyl, i-propyl, cyclopropyl, cyclopropylmethyl, 1-propenyl, allyl, and vinyl;
- R2 and R4 are selected from the group consisting of H, methyl, ethyl, n-propyl, i-propyl, acetyl, propionyl, butyryl, cyclopropanecarbonyl, and isobutyryl;
- R3 is selected from the group consisting of H, acetyl, propionyl, butyryl, cyclopropanecarbonyl, and isobutyryl;
- and R5 is selected from the group consisting of H, methyl, ethyl, n-propyl, i-propyl, acetyl, propionyl, butyryl, cyclopropanecarbonyl, and isobutyryl.
A method for treating a disease characterized by undesirable mitosis and/or undesirable angiogenesis, said method comprising administering to a mammal having said disease an effective amount of a compound of the formula below:
- wherein:
- A is selected from the group consisting of CH2, NR4, C═O, C═NOH, CHNHCR5 and CHOH;
- B is selected from the group consisting of CH2 and C═O;
- R1 is selected from the group consisting of H, methyl, ethyl, n-propyl, i-propyl, cyclopropyl, cyclopropylmethyl, 1-propenyl, allyl, and vinyl;
- R2 and R4 are selected from the group consisting of H, methyl, ethyl, n-propyl, i-propyl, acetyl, propionyl, butyryl, cyclopropanecarbonyl, and isobutyryl;
- R3 is selected from the group consisting of H, acetyl, propionyl, butyryl, cyclopropanecarbonyl, and isobutyryl;
- and R5 is selected from the group consisting of H, methyl, ethyl, n-propyl, i-propyl, acetyl, propionyl, butyryl, cyclopropanecarbonyl, and isobutyryl.
Dependencies are inferred from the claim text.