Indane estrogen receptor modulators and uses thereof

1. A compound of Formula (VI), or a pharmaceutically acceptable salt, or solvate thereof:

wherein,

R 1 is H, F, C 1 -C 6 alkyl, or C 1 -C 6 fluoroalkyl;

is azetidinyl or pyrrolidinyl;

each R 4 is independently selected from F, Cl, —OH, —CH 3 , —CF 3 , —OCF 3 and —OCH 3 ;

each R 5 is independently selected from halogen, —CN, —OH, —OR 7 , substituted or unsubstituted C 1 -C 6 alkyl, and substituted or unsubstituted C 1 -C 6 fluoroalkyl;

each R 6 is independently selected from halogen, —CN, —OH, —OR 7 , —SR 7 , —S(═O)R 8 , —S(═O) 2 R 8 , —NHS(═O) 2 R 8 , substituted or unsubstituted C 1 -C 6 alkyl, and substituted or unsubstituted C 1 -C 6 fluoroalkyl;

each R 7 is independently selected from H, —C(═O)R 8 , —C(═O)OR 8 , —C(═O)NHR 8 , C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, or C 1 -C 6 fluoroalkyl;

R 8 is independently selected from C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, or C 1 -C 6 fluoroalkyl;

each R 9 is independently selected from F, Cl, —OH, C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, C 1 -C 4 fluoroalkoxy, C 1 -C 4 alkoxy, and C 1 -C 4 heteroalkyl;

each R 10 is independently H, F, or C 1 -C 4 alkyl;

or both R 10 are taken together with the carbon atom to which they are attached to form —C(═O)—;

X is —O—;

m is 0, or 1;

n is 0, 1, or 2;

p is 0, 1, 2, or 3;

t is 1, or 2;

wherein substituted groups are substituted with one or more groups selected from halogen, —CN, —NH 2 , —OH, —NH(CH 3 ), —N(CH 3 ) 2 , —CH 3 , —CH 2 CH 3 , —CF 3 , —OCH 3 , and —OCF 3 .

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is H or C 1 -C 4 alkyl;

each R 10 is independently H, F, or —CH 3 ;

each R 5 is independently selected from halogen, —CN, —OH, —OR 7 , substituted or unsubstituted C 1 -C 6 alkyl, and substituted or unsubstituted C 1 -C 6 -fluoroalkyl;

each R 6 is independently selected from halogen, —CN, —OH, —OR 7 , —SR 7 , —S(═O)R 8 , —S(═O) 2 R 8 , —NHS(═O) 2 R 8 , substituted or unsubstituted C 1 -C 6 alkyl, and substituted or unsubstituted C 1 -C 6 fluoroalkyl.

3. The compound of claim 2 , wherein the compound of Formula (VI) has the structure of Formula (VII) or Formula (VIII):

wherein,

n is 0, or 1;

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein:

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein:

6. The compound of claim 1 , wherein the compound of Formula (VI) has the structure of Formula (IX) or Formula (X):

wherein

q is 1;

n is 0, or 1;

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is H or —CH 3 ;

each R 9 is independently selected from F, Cl, —OH, —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CF 3 , —CH 2 CF 3 , —OCF 3 , —OCH 2 CF 3 , —OCH 3 , —OCH 2 CH 3 , —CH 2 OCH 3 , —CH 2 OCH 2 CH 3 , and —CH 2 OH;

t is 1, or 2.

8. A compound that is:

2-(4-Hydroxyphenyl)-1-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2,3-dihydro-1H-inden-5-ol;

2-(4-Hydroxyphenyl)-1-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)-2,3-dihydro-1H-inden-5-ol;

2-(3-Hydroxyphenyl)-1-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)-2,3-dihydro-1H-inden-5-ol;

1-(4-((S)-2-((R)-3-Methylpyrrolidin-1-yl)propoxy)phenyl)-2-phenyl-2,3-dihydro-1H-inden-5-ol;

4-Fluoro-2-(4-hydroxyphenyl)-1-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)-2,3-dihydro-1H-inden-5-ol;

2-(4-Fluorophenyl)-1-(4-((S)-2-((R)-3-methylpyrrolidin-1-yl)propoxy)phenyl)-2,3-dihydro-1H-inden-5-ol;

2-Phenyl-1-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-2,3-dihydro-1H-inden-5-ol;

or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

10. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is formulated for intravenous injection, subcutaneous injection, oral administration, or topical administration.

11. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is a tablet, a pill, a capsule, a liquid, a suspension, a gel, a dispersion, a solution, an emulsion, an ointment, or a lotion.