Steroidal quinols and their use for estrogen replacement therapy

• US 7,300,926 B2
• Filed: 09/17/2003
• Issued: 11/27/2007
• Est. Priority Date: 04/01/2002
• Status: Active Grant

• Current Assignee: University of North Texas Health Science Center (University of North Texas)
• Original Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida), University of North Texas Health Science Center (University of North Texas)
• Inventors: Prokai, Laszlo, Prokai, Katalin, Simpkins, James
• Primary Examiner(s): Badio; Barbara P.
• Application Number:
  US10/666,191
• Publication Number:
  US 20040138190A1
• Time in Patent Office: 1,532 Days
• Field of Search: 552/612, 514/178
• US Class Current: 514/178
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/566 having an oxo group in position 17, e.g. estrone
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

The present invention relates to novel estrogen-related steroidal quinols and their use as drugs for estrogen replacement therapy. The quinols of the present invention provide improved physicochemical properties, increased bioavailability, and improved distribution into tissues, bone, in the cardiovascular system, and in the CNS (central nervous system) with only a slight estrogenic action or no estrogenic action in the uterus. The compounds are suitable for the production of pharmaceutical agents for use in numerous indications (for example, estrogen replacement therapy, prevention and treatment of osteoporosis).

Claims

1. A method for providing estrogen replacement therapy to a patient while minimizing undesirable side effects associated with estrogen treatment or therapy, wherein said method comprises administering to the patient an effective amount of a quinol that is converted to a biologically active estrogen compound in vivo, wherein the quinol has the general structure:

2. The method according to claim 1, further comprising administering the quinol by a route selected from the group consisting of oral, buccal, intramuscular, transdermal, intravenous, and subcutaneous.

3. The method according to claim 1, wherein the biologically active estrogen compounds are provided to the patient for the treatment of symptoms, diseases, or conditions associated with menopause, wherein the symptoms, diseases, or conditions associated with menopause is any one or more selected from the group consisting of:

irregular period, hot flashes, increased risk of vaginal and/or bladder infection, urge incontinence, stress incontinence, fatigue, depression, loss of muscle mass, increased fat tissue, thinning and loss of skin elasticity, loss of bone tissue, and impaired cognition.

4. The method according to claim 1, wherein the biologically active estrogen compounds are provided to the patient for the treatment of conditions associated with the bone, wherein the conditions associated with the bone is any one or more selected from the group consisting of:

osteoporosis, osteomyelitis, ischemic bone disease, fibrous dysplasia, rickets, Cushing'"'"'s syndrome and osteoarthritis.

5. The method according to claim 1, wherein the biologically active estrogen compounds are provided to the patient for treatment of conditions associated with heart disease, wherein the conditions associated with heart disease is any one or more selected from the group consisting of:

stroke, cardiac ischemia, myocardial infarction, chronic or acute heart failure, cardiac dysrhymias, artrial fibrillation, paroxysmal tachycardia, ventricular fibrillation and congestive heart failure.

6. A quinol that is converted to a biologically active estrogen compound via enzyme catalyzed reduction, said quinol having the general structure

7. A pharmaceutical composition comprising a quinol that is converted to a biologically active estrogen compound via enzyme catalyzed reduction, wherein said composition further comprises a pharmaceutically acceptable carrier, wherein said quinol has the general structure: