Substituted 10,11-benzo[b]fluoren-10-ones as estrogenic agents

• US 20030087955A1
• Filed: 05/15/2002
• Published: 05/08/2003
• Est. Priority Date: 05/17/2001
• Status: Active Grant

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Miller, Christopher P., Keith, James C. Jr., Harris, Heather A., Collini, Michael D.
• Granted Patent: US 6,589,980 B2
• Time in Patent Office: Days
• US Class Current: 514/453
• CPC Class Codes: C07D 493/04 Ortho-condensed systems

Abstract

This invention provides estrogen receptor modulators of formula 1, having the structure

wherein

X, Y¹, Y², Y³, Y⁴, Z¹, Z², Z³, and Z⁴ are as defined in the specification, or a pharmaceutically acceptable salt thereof.

Claims

1. A compound of formula 1, having the structure

2. The compound according to claim 1, wherein Y¹, Y⁴, Z¹, Z², Z³, and Z⁴ are hydrogen, or —

OR;

with at least one of Y¹, Y⁴, Z¹, Z², Z³, and Z⁴ not being —

OR.

3. The compound according to claim 2, wherein R is hydrogen or alkyl of 1-6 carbon atoms.

4. A compound which is 2,6-dihydroxy-8-methoxy-10,11-dioxa-benzo[b]fluoren-5-one or a pharmaceutically acceptable salt thereof.

5. A compound which is 2,8-dihydroxy-10,11-dioxa-benzo[b]fluoren-5-one or a pharmaceutically acceptable salt thereof.

6. A method of treating or inhibiting osteoporosis or inhibiting bone demineralization in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula 1, having the structure

7. A method of treating or inhibiting inflammatory bowel disease, Crohn'"'"'s disease, ulcerative proctitis, or colitis in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula 1, having the structure

8. A method of treating or inhibiting prostatic hypertrophy, uterine leiomyomas, breast cancer, endometriosis, endometrial cancer, polycystic ovary syndrome, endometrial polyps, benign breast disease, adenomyosis, ovarian cancer, melanoma, prostrate cancer, colon cancer, glioma or astioblastomia in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula 1, having the structure

9. A method of lowering cholesterol, triglycerides, Lp(a), or LDL levels;

inhibiting or treating hypercholesteremia;

hyperlipidemia;

cardiovascular disease;

atherosclerosis;

peripheral vascular disease;

restenosis, or vasospasm;

or inhibiting vascular wall damage from cellular events leading toward immune mediated vascular damage in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula 1, having the structure

10. A method of treating or inhibiting providing cognition enhancement or neuroprotection;

or treating or inhibiting senile dementias, Alzheimer'"'"'s disease, cognitive decline, or neurodegenerative disorders in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula 1, having the structure

11. A method of treating or inhibiting free radical induced disease states in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula 1, having the structure

12. A method of treating or inhibiting vaginal or vulvar atrophy;

atrophic vaginitis;

vaginal dryness;

pruritus;

dyspareunia;

dysuria;

frequent urination;

urinary incontinence;

urinary tract infections in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula 1, having the structure

13. A method of treating or inhibiting vasomotor symptoms in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula 1, having the structure

14. A method of treating or inhibiting menopausal or postmenopausal disorders in a mammal in need thereof, which comprises providing to said mammal an effective amount of a compound of formula 1, having the structure

15. A pharmaceutical composition which comprises a compound of formula 1, having the structure