Compositions and methods for treating estrogen-related medical disorders

Patent metadata

Field	Value
Publication number	US-10888545-B2
Application number	US-201815885273-A
Country	US
Kind code	B2
Filing date	Jan 31, 2018
Priority date	Oct 24, 2012
Publication date	Jan 12, 2021
Grant date	Jan 12, 2021

Abstract

Disclosed herein are methods for treatment of estrogen-related medical disorders. The methods of treatment may comprise administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of at least one compound of formula (I)

or a pharmaceutically acceptable salt thereof.

First claim

What is claimed is:

1. A method for treatment of an estrogen-related medical disorder, the method comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of at least one compound of formula (I)

or a pharmaceutically acceptable salt thereof,
wherein
R 1 is selected from the group consisting of hydrogen, alkyl, —SO 3 R x1 , —PO 3 R y1 R z1 , and —C(═O)R a ;
R 2 is selected from the group consisting of halo and —OR 3 ;
R 3 is selected from the group consisting of hydrogen, alkyl, —SO 3 R x1 , —PO 3 R y1 R z1 , and —C(═O)R a ;
A 1 is —OR b2 or —C(═O)R b3 ;
R b3 is selected from the group consisting of cycloalkyl, and phenyl substituted with 1, 2, or 3 halo;
R b2 is selected from the group consisting of alkyl, cycloalkyl, and phenyl substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo and —OR 4 ;
R 4 is selected from the group consisting of hydrogen, alkyl, —SO 3 R x1 , —PO 3 R y1 R z1 , and —C(═O)R a ;
R, at each occurrence, is independently selected from the group consisting of —OH and alkyl; and
R x1 , R y1 and R z1 are, at each occurrence, independently selected from the group consisting of hydrogen and a pharmaceutically acceptable cation;
provided that the compound of formula (I) contains at least one group selected from —OR 3 and —OR 4 ;
provided that 2-(4-fluorophenyl)-3-(4-hydroxyphenoxy)benzo[b]thiophen-6-ol is excluded from the compound of formula (I),
wherein the estrogen-related medical disorder is Alzheimer's Disease.

2. The method of claim 1 , wherein the at least one compound of formula (I) is
3-(4-fluorophenyl)-2-(4-hydroxyphenoxy)benzo[b]thiophen-6-ol;
or a pharmaceutically acceptable thereof.

3. A method for treatment of an estrogen-related medical disorder, the method comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of at least one compound of formula (II)

or a pharmaceutically acceptable salt thereof,
wherein
A 2 is —O— or —C(═O)—;
R 5 and R 6 are each independently selected from the group consisting of hydrogen, alkyl, —SO 3 R x2 , —PO 3 R y2 R y3 , and —C(═O)R c ;
R c is selected from the group consisting of —OH and alkyl;
R x2 , R y2 and R z2 are each independently selected from the group consisting of hydrogen and a pharmaceutically acceptable cation; and
X is halogen or trifluoromethyl;
provided that 2-(4-fluorophenyl)-3-(4-hydroxyphenoxy)benzo[b]thiophen-6-ol is excluded from the compound of formula (II),
wherein the estrogen-related medical disorder is Alzheimer's Disease.

4. The method of claim 3 , wherein the at least one compound of formula (II) is 3-(4-fluorophenyl)-2-(4-hydroxyphenoxy)benzo[b]thiophen-6-ol or a pharmaceutically acceptable thereof.

5. The method of claim 1 , wherein the compound has formula (I-vii)

wherein
R 1 is selected from the group consisting of hydrogen, alkyl, —SO 3 R x1 , —PO 3 R y1 R z1 , and —C(═O)R a ;
R 2 is selected from the group consisting of halo and —OR 3 ;
R 3 is selected from the group consisting of hydrogen, alkyl, —SO 3 R x1 , —PO 3 R y1 R z1 , and —C(═O)R a ;
R 4 is selected from the group consisting of hydrogen, alkyl, —SO 3 R x1 , —PO 3 R y1 R z1 , and —C(═O)R a ;
R a , at each occurrence, is independently selected from the group consisting of —OH and alkyl; and
R x1 , R y1 and R z1 are, at each occurrence, independently selected from the group consisting of hydrogen and a pharmaceutically acceptable cation.

6. The method of claim 5 , wherein the compound has formula (I-viii),

wherein R 1 and R 4 are as defined in claim 5 .

7. The method of claim 5 , wherein the compound has formula (I-ix),

wherein R 1 is as defined in claim 5 .

8. The method of claim 5 , wherein the compound has formula (I-x),

Assignees

• Univ Illinois

Inventors

• Thatcher Gregory R
• Tonetti Debra
• Molloy Mary Ellen
• Michalsen Bradley
• Qin Zihui
• Xiong Rui

Classifications

• G01N33/57595

  involving intracellular compounds · CPC title

• C07D333/64

  Oxygen atoms · CPC title

• A61K31/381 Primary

  having five-membered rings · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N2333/91205

  Phosphotransferases in general · CPC title