5-(1',1'-cycloalkyl/alkenyl)methylidene 1,2-dihydro-5H-chromeno-[3,4-f]-quinolines as selective progesterone receptor modulator compounds

A method of modulating the fertility of an individual, comprising administering to the individual a pharmaceutically effective amount of a compound represented by the formula:

• wherein:
• R1 is selected from the group of hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, COR5, CO2R5, SO2R5, and CONR5R6;
• R2 and R3 each independently is selected from the group of hydrogen, C1-C6 alkyl, and C1-C6 haloalkyl;
• or
• R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
• R4 is selected from the group of hydrogen, F, Cl, Br, CN, OR5, C—C4 alkyl, C1-C4 haloalkyl, and C—C4 heteroalkyl;
• R5 and R6 each is independently selected from the group of hydrogen, C1-C4 alkyl, C1-C4 heteroalkyl, and C1-C4 haloalkyl;
• R7 through R9 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR5, NR5R6, SR5, COR5, CO2R5, CONR5R6, C1-C8 alkyl, C1-C8 heteroalkyl, C1-C8 haloalkyl, C2-C8 alkenyl, C2-C8 alkynyl;
• R10 through R15 each independently is selected from the group of hydrogen, F, Cl, Br, OR5, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 heteroalkyl;
• or
• R12 and R14 taken together form a bond, when Y is CR14R15;
• or
• R10 and R14 taken together form a bond, when Z is CR14R15;
• R16 and R17 each independently is selected from the group of C1-C4 alkyl and C1-C4 haloalkyl;
• R18 and R19 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR5, NR5R6, SR5, COR5, C1-C4 alkyl, C1-C4 heteroalkyl, C1-C4 haloalkyl and C2-C4 alkenyl;
• Y and Z each independently is selected from the group of O, S, NR6 and CR14R15;
• and
• n is 0, 1, 2, or 3;
• or a pharmaceutically acceptable salt thereof.

A method of treating an individual having a hormone-dependent cancer, comprising administering to the individual a pharmaceutically effective amount of a compound represented by the formula:

• wherein:
• R1 is selected from the group of hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, COR5, CO2R5, SO2R5, and CONR5R6;
• R2 and R3 each independently is selected from the group of hydrogen, C1-C6 alkyl, and C1-C6 haloalkyl;
• or
• R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
• R4 is selected from the group of hydrogen, F, Cl, Br, CN, OR5, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 heteroalkyl;
• R5 and R6 each is independently selected from the group of hydrogen, C1-C4 alkyl, C1-C4 heteroalkyl, and C1-C4 haloalkyl;
• R7 through R9 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR5, NR5R6, SR5, COR5, CO2R5, CONR5R6, C1-C8 alkyl, C1-C8 heteroalkyl, C1-C8 haloalkyl, C2-C8 alkenyl, C2-C8 alkynyl;
• R10 through R15 each independently is selected from the group of hydrogen, F, Cl, Br, OR5, C—C4 alkyl, C1-C4 haloalkyl, and C1-C4 heteroalkyl;
• or
• R12 and R14 taken together form a bond, when Y is CR14R15;
• or
• R10 and R14 taken together form a bond, when Z is CR14R15;
• R16 and R17 each independently is selected from the group of C1-C4 alkyl and C1-C4 haloalkyl;
• R18 and R19 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR5, NR5R6, SR5, COR5, C1-C4 alkyl, C—C4 heteroalkyl, C1-C4 haloalkyl and C2-C4 alkenyl;
• Y and Z each independently is selected from the group of O, S, NR6 and CR14R15;
• and
• n is 0, 1, 2, or 3;
• or a pharmaceutically acceptable salt thereof.

A method of modulating a progesterone receptor in an individual, comprising administering to the individual a compound represented by the formula:

• wherein:
• R1 is selected from the group of hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, COR5, CO2R5, SO2R5, and CONR5R6;
• R2 and R3 each independently is selected from the group of hydrogen, C1-C6 alkyl, and C1-C6 haloalkyl;
• or
• R2 and R3 taken together form a cycloalkyl ring of from three to twelve carbons;
• R4 is selected from the group of hydrogen, F, Cl, Br, CN, OR5, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 heteroalkyl;
• R5 and R6 each is independently selected from the group of hydrogen, C1-C4 alkyl, C1-C4 heteroalkyl, and C1-C4 haloalkyl;
• R7 through R9 each independently is selected from the group of hydrogen, F, Cl, Br, I, NO2, CN, OR5, NR5R6, SR5, COR5, CO2R5, CONR5R6, C1-C8 alkyl, C1-C8 heteroalkyl, C1-C8 haloalkyl, C2-C8 alkenyl, C2-C8 alkynyl;
• R10 through R15 each independently is selected from the group of hydrogen, F, Cl, Br, OR5, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 heteroalkyl;
• or
• R12 and R14 taken together form a bond, when Y is CR14R15;
• or
• R10 and R14 taken together form a bond, when Z is CR14R15;
• R16 and R17 each independently is selected from the group of C1-C4 alkyl and C1-C4 haloalkyl;
• R18 and R19 each independently is selected from the group of hydrogen, F, Cl, Br, CN, OR5, NR5R6, SR5, COR5, C1-C4 alkyl, C1-C4 heteroalkyl, C1-C4 haloalkyl and C2-C4 alkenyl;
• Y and Z each independently is selected from the group of O, S, NR6 and CR14R15;
• and
• n is 0, 1, 2, or 3;
• or a pharmaceutically acceptable salt thereof, wherein
• the amount of compound administered is effective to modulate a progesterone receptor.