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US 7,842,680 B2Granted
Diene and triene compounds and formulations
AssigneeHarbor BioSciences, Inc.
InventorsHenry A. Lardy, Padma Marwah, Ashok Marwah
Life of this patent
Estimating the term…
Abstract
The instant invention provides potent antiandrogen compounds, such as 3β-acetoxyandrost-1,5-diene-17-ethylene ketal and 3β-hydroxyandrost-1,5-diene-17-ethylene ketal, and methods for their use in the prevention and treatment of biological conditions mediated by androgen receptors. Thus, for example, compounds of the invention are useful in the prevention and treatment of prostrate cancer. Furthermore, it has been discovered that compounds of the invention are useful in the prevention and treatment of androgen-independent cancers such as androgen-independent prostrate cancer. Finally, inventive compounds may be used to treat antiandrogen induced withdrawal syndrome.
Claims17
A compound of the structure
- or a pharmaceutically acceptable salt of the compound and wherein,
- A is —C(O)— or —CR9R10—;
- G is —C(O)— or —CR3R4—;
- K is —CR1R2—;
- R and R′ independently are —F, —Cl, —Br, —I, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkene, substituted or unsubstituted lower alkyne, —CN, —COOR14, —C(O)NR14R15, —NO2, —NR14R15, —NR14—C(O)—R15, —OH, substituted or unsubstituted lower alkoxy, and —S(O)0-2R14;
- R1 is —OR11, —C(O)—R12, —C(O)—NR12R13, —C(O)—OR12, —C(S)—R12, —C(S)—OR12 or —S(O)0-2—R12;
- R2 and R4 independently are —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkene or substituted or unsubstituted lower alkyne;
- R3 and R5 independently are —H, —F, —Cl, —Br, —I, substituted and unsubstituted lower alkyl, substituted and unsubstituted lower alkene, substituted and unsubstituted lower alkyne, —CN, —COOR14, —C(O)NR14R15, —NO2, —NR14R15, —NR14—C(O)—R15, —OH, substituted and unsubstituted lower alkoxy or —S(O)0-2R14;
- R6 is —H, —F, —Cl, —Br, —I, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkene, substituted or unsubstituted lower alkyne, —CN, —COOR14, —C(O)NR14R15, —NO2, —NR14R15, —NR14—C(O)—R15, —OH, substituted and unsubstituted lower alkoxy or and —S(O)0-2R14;
- R7 and R8 independently are —H or substituted or unsubstituted lower alkyl;
- R9 is —OH or substituted or unsubstituted lower alkoxy;
- R10 is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkene, substituted or unsubstituted lower alkyne, substituted or unsubstituted —S(O)0-2(lower alkyl), or R9 and R10, together with the carbon to which they are attached, form a 5-, 6-, or 7-member heterocyclyl or cycloalkyl group;
- R11 is —H, substituted or unsubstituted alkyl, substituted or unsubstituted alkene, substituted or unsubstituted alkyne, —C(O)—R12, —C(O)—NR12R13, —C(O)—OR12, —C(S)—R12, —NR12R13, —S(O)2—R12, —S(O)2—OR12, and —P(O)(OR12)(OR13)0-1;
- R12 and R13 independently are —H, substituted or unsubstituted alkyl, substituted or unsubstituted alkene, substituted or unsubstituted alkyne, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl;
- R14 and R15 independently are —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkene, substituted or unsubstituted lower alkyne, substituted or unsubstituted C6-10 aryl, or substituted or unsubstituted C7-12 arylalkyl;
- n is 0, 1, or 2;
- and
- n′ is 0, 1 or 2.
15 more elements
A pharmaceutical formulation comprising one or more excipients and a compound of the structure
- or a pharmaceutically acceptable salt of the compound and wherein,
- A is —C(O)— or —CR9R10—;
- G is —C(O)— or —CR3R4—;
- K is —CR1R2—;
- R and R′ independently are —F, —Cl, —Br, —I, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkene, substituted or unsubstituted lower alkyne, —CN, —COOR14, —C(O)NR14R15, —NO2, —NR14R15, —NR14—C(O)—R15, —OH, substituted or unsubstituted lower alkoxy, and —S(O)0-2R14;
- R1 is —OR11, —C(O)—R12, —C(O)—NR12R13, —C(O)—OR12, —C(S)—R12, —C(S)—OR12 or —S(O)0-2—R12;
- R2 and R4 independently are —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkene or substituted or unsubstituted lower alkyne;
- R3 and R5 independently are —H, —F, —Cl, —Br, —I, substituted and unsubstituted lower alkyl, substituted and unsubstituted lower alkene, substituted and unsubstituted lower alkyne, —CN, —COOR14, —C(O)NR14R15, —NO2, —NR14R15, —NR14—C(O)—R15, —OH, substituted and unsubstituted lower alkoxy or —S(O)0-2R14;
- R6 is —H, —F, —Cl, —Br, —I, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkene, substituted or unsubstituted lower alkyne, —CN, —COOR14, —C(O)NR14R15, —NO2, —NR14R15, —NR14—C(O)—R15, —OH, substituted and unsubstituted lower alkoxy or and —S(O)0-2R14;
- R7 and R8 independently are —H or substituted or unsubstituted lower alkyl;
- R9 is —OH or substituted or unsubstituted lower alkoxy;
- R10 is substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkene, substituted or unsubstituted lower alkyne, substituted or unsubstituted —S(O)0-2(lower alkyl), or R9 and R10, together with the carbon to which they are attached, form a 5-, 6-, or 7-member heterocyclyl or cycloalkyl group;
- R11 is —H, substituted or unsubstituted alkyl, substituted or unsubstituted alkene, substituted or unsubstituted alkyne, —C(O)—R12, —C(O)—NR12R13, —C(O)—OR12, —C(S)—R12, —NR12R13, —S(O)2—R12, —S(O)2—OR12, and —P(O)(OR12)(OR13)0-1;
- R12 and R13 independently are —H, substituted or unsubstituted alkyl, substituted or unsubstituted alkene, substituted or unsubstituted alkyne, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl;
- R14 and R15 independently are —H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkene, substituted or unsubstituted lower alkyne, substituted or unsubstituted C6-10 aryl, or substituted or unsubstituted C7-12 arylalkyl;
- n is 0, 1, or 2;
- and
- n′ is 0, 1 or 2.
15 more elements
Dependencies are inferred from the claim text.