Estrogen receptor modulators and uses thereof

• US 7,989,487 B2
• Filed: 07/06/2007
• Issued: 08/02/2011
• Est. Priority Date: 07/06/2006
• Status: Expired due to Fees

• Current Assignee: Rutgers University
• Original Assignee: University of Medicine and Dentistry of New Jersey (State of New Jersey)
• Inventors: Ai, Ni, Wang, Nina Ching Y., Welsh, William J.
• Primary Examiner(s): Henley, III; Raymond
• Application Number:
  US12/307,565
• Publication Number:
  US 20100152271A1
• Time in Patent Office: 1,488 Days
• Field of Search: 514/419, 514/679
• US Class Current: 514/419
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/122 having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
• CPC Class Codes: A61K 31/4035 Isoindoles, e.g. phthalimide
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

A method for preventing, diagnosing, or treating a condition mediated by an estrogen receptor by administering to a patient in need thereof an effective amount of a compound of formula I, II, or a combination thereof: wherein R1, R3, R4, and R5 are independently selected from H, OH, and OR_a; R2 is selected from H, OH, and (C═O)(C_1-7)alkyl; R_a is (C_1-7)alkyl or (C═O)(C_1-7)alkyl; or a derivative of the compound selected from N-oxide derivatives, prodrug derivatives, protected derivatives, isomers, and mixtures of isomers of the compound; or a pharmaceutically acceptable salt or solvate of the compound or the derivative. Compounds of formula I and II and pharmaceuticals compositions thereof are also presented.

Claims

1. A method for diagnosing or treating a condition mediated by an estrogen receptor, said method comprising administering to a patient in need thereof an effective amount of a compound of formula I, II, or a combination thereof:

2. The method of claim 1, wherein R1 is OH, R2 is (C═

O)CH₂CH₃, and R3 is H.

3. The method of claim 1, wherein R4 is OH and R5 is H.

4. The method of claim 1, wherein said condition is selected from the group consisting of osteoporosis, atheroschlerosis, estrogen-mediated cancers, Tumer'"'"'s syndrome, benign prostate hyperplasia, prostate cancer, elevated cholesterol, restenosis, endometriosis, uterine fribroid disease, skin and/or vagina atrophy, Alzheimer'"'"'s disease, androgenic alopecia, pregnancy, and pre- and post-menopausal associated conditions.

5. The method of claim 1, wherein said estrogen-mediated cancer is breast cancer or endometrial cancer.

6. A compound of formula I or II:

7. A pharmaceutical composition comprising an effective amount of the compound of claim 6 and a pharmaceutically acceptable carrier.

8. A method for diagnosing a condition in a patient as an estrogen receptor-mediated condition comprising (a) exposing a sample from the patient affected by the condition to a labeled compound of formula I or II: