Estrogen receptor modulators

A method of inhibiting the growth of a cell, comprising

• identifying a cell having an estrogen receptor alpha that mediates a growth characteristic of the cell;
• and
• contacting the cell with an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:
• wherein:
• X1, Y1 and Z1 are each independently C or N;
• with the first proviso that at least one of X1, Y1 and Z1 is N;
• with the second proviso that each of X1, Y1 and Z1 is uncharged;
• with third proviso that two of the dotted lines indicate double bonds;
• with the fourth proviso that the valencies of X1, Y1 and Z1 can be each independently satisfied by attachment to a substituent selected from H and R12;
• X2 is O, NH or S;
• A1 is selected from the group consisting of an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl and an optionally substituted heterocyclyl;
• R1 is selected from the group consisting of an optionally substituted C1-6 alkyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, an optionally substituted cycloalkyl(C1-6 alkyl), an optionally substituted cycloalkenyl(C1-6 alkyl), an optionally substituted aryl(C1-6 alkyl), an optionally substituted heteroaryl(C1-6 alkyl) and an optionally substituted heterocyclyl(C1-6 alkyl);
• R2 and R3 are each independently selected from the group consisting of hydrogen, halogen, an optionally substituted C1-6 alkyl and an optionally substituted C1-6 haloalkyl;
• or R2 and R3 together with the carbon to which R2 and R3 are attached form an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl or an optionally substituted heterocyclyl;
• R4 and R5 are each independently selected from the group consisting of hydrogen, halogen, an optionally substituted C1-6 alkyl and an optionally substituted C1-6 haloalkyl;
• or R4 and R5 together with the carbon to which R4 and R5 are attached form an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl or an optionally substituted heterocyclyl;
• R6, R7, R8 and R9 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, an optionally substituted alkyl, an optionally substituted alkoxy, an optionally substituted haloalkyl, an optionally substituted mono-substituted amine, and an optionally substituted di-substituted amine;
• R10 is hydrogen, deuterium, halogen, an optionally substituted alkyl, or an optionally substituted cycloalkyl;
• R11 is hydrogen or an optionally substituted C1-6 alkyl;
• and
• R12 is hydrogen, halogen, an optionally substituted C1-3 alkyl, an optionally substituted C1-3 haloalkyl or an optionally substituted C1-3 alkoxy;
• provided that when R11 is hydrogen or methyl, X1 is NH, Y1 and Z1 are each C, X2 is O, A1 is a phenyl, 2-fluorophenyl, or 2,6-difluorophenyl, both R2 and R3 are methyl or one of R2 and R3 is hydrogen and the other of R2 and R3 is methyl, and R4, R5, R6, R7, R8, R9 and R10 are each hydrogen, then R1 cannot be 2-hydroxyethyl, 2-methylpropyl, 2-fluoro-2-methylpropyl, 3-fluoro-2-methylpropyl, 3-hydroxy-2-methylpropyl or 2-fluoro-3-hydroxy-2-methylpropyl.