Estrogen receptor modulators

1 . A compound of the formula:

wherein

R 1 is fluoro, OR 4 , N(R 4 ) 2 , C (1-3) alkyl, C (2-5) alkenyl, C (2-5) alkynyl, C (1-3) acyl or cyano;

R 2 is hydrogen, fluoro, C (1-3) alkyl, C (2-5) alkenyl or C (2-5) alkynyl;

R 3 is hydrogen, fluoro, C (1-3) alkyl, C (2-5) alkenyl, C (2-5) alkynyl, or CR 1 R 2 R 5 ;

or R 2 and R 3 taken together represent a carbonyl group;

each R 4 is independently hydrogen or C (1-3) alkyl;

R 5 is hydrogen, fluoro, C (1-3) alkyl, C (2-5) alkenyl, C (2-5) alkynyl, or cyano;

R 17 is hydrogen, C (1-5) alkyl, C (1-5) acyl, C (2-5) alkenyl, or C (2-5) alkynyl;

and the pharmaceutically acceptable salts and stereoisomers thereof.

2 . The compound of claim 1 wherein

R 1 is fluoro, C (1-3) alkyl, C (2-5) alkenyl or C (2-5) alkynyl;

R 2 is hydrogen, methyl or fluoro;

R 3 is hydrogen, methyl or fluoro;

R 17 is hydrogen, C (1-5) alkyl, C (2-5) alkenyl or C (2-5) alkynyl;

and the pharmaceutically acceptable salts and stereoisomers thereof.

3 . The compound of claim 2 wherein

R 1 is fluoro, methyl, vinyl or ethynyl;

R 2 is hydrogen or fluoro;

R 3 is hydrogen or fluoro;

R 4 is hydrogen or methyl;

R 17 is hydrogen, methyl or ethynyl;

and the pharmaceutically acceptable salts and stereoisomers thereof.

4 . The compound of claim 1 selected from

1 9-methyl-3β,17β-androst-5-ene diol;

3β,17β, 19-androst-5-ene triol;

19-methyl-3β,17β, 19-androst-5-ene triol

19-fluoro-3β,17β-androst-5-ene diol;

19-cyano-3β,17β-androst-5-ene diol;

19, 19, 19-trifluoro-3β,17β-androst-5-ene diol;

19-vinyl-3β,17β-androst-5-ene diol;

19-ethynyl-3β, 17β-androst-5-ene diol;

17α-ethynyl-3β,17β,19-androst-5-ene triol;

17α-ethynyl- 19-methyl-3β,17β-androst-5-ene diol;

17α-ethynyl- 19-methyl-3β-hydroxy-17β-methoxy-androst-5-ene;

17-O-methyl-19-methyl-3β,17β-androst-5-ene diol;

17-O-methyl-17α-ethynyl-19-methyl-3β,17β-androst-5-ene diol;

or the pharmaceutically acceptable salts and stereoisomers thereof.

5 . A method of treating a disease selected from: bone loss, bone fractures, osteoporosis, metastatic bone disease, Paget's disease, periodontal disease, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, anxiety, depression resulting from an estrogen deficiency, inflanmmation, inflammatory bowel disease, sexual dysfunction, hypertension, retinal degeneration or estrogen dependent cancer in a mammal in need thereof by administering a therapeutically effective amount of a compound according to claim 1 .

6 . The method of claim 5 wherein the disease is hot flashes.

7 . The method of claim 5 further comprising another agent selected from: an organic bisphosphonate; a cathepsin K inhibitor; an estrogen; an estrogen receptor modulator; an androgen receptor modulator; an inhibitor of osteoclast proton ATPase; an inhibitor of HMG-CoA reductase; an integrin receptor antagonist; an osteoblast anabolic agent; calcitonin; Vitamin D; a synthetic Vitamin D analogue; or a selective serotonin reuptake inhibitor; an aromatase inhibitor; or a pharmaceutically acceptable salt or mixture thereof.

8 . A pharmaceutical composition comprising a compound of claim 1 and another agent selected from: an organic bisphosphonate; a cathepsin K inhibitor; an estrogen; an estrogen receptor modulator; an androgen receptor modulator; an inhibitor of osteoclast proton ATPase; an inhibitor of HMG-CoA reductase; an integrin receptor antagonist; an osteoblast anabolic agent; calcitonin; Vitamin D; a synthetic Vitamin D analogue; or a selective serotonin reuptake inhibitor; an aromatase inhibitor; or a pharmaceutically acceptable salt or mixture thereof.

9 . The composition of claim 8 wherein the agent is an organic bisphosphonate.

10 . The composition of claim 9 wherein the organic bisphosphonate is alendronate.