2-ethyl and 2-ethylidene-19-nor-vitamin D compounds

• US 7,468,361 B2
• Filed: 08/16/2007
• Issued: 12/23/2008
• Est. Priority Date: 05/31/2000
• Status: Expired due to Fees

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: DeLuca, Hector F., Sicinski, Rafal R.
• Primary Examiner(s): Badio; Barbara P
• Application Number:
  US11/839,586
• Publication Number:
  US 20080032956A1
• Time in Patent Office: 495 Days
• Field of Search: 514/167
• US Class Current: 514/167
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• 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
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07C 401/00 : Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation

Abstract

Biologically active 19-nor vitamin D analogs substituted at C-2 in the A-ring with an ethylidene or an ethyl group. These compounds have preferential activity on mobilizing calcium from bone and either high or normal intestinal calcium transport activity which allows their in vivo administration for the treatment of metabolic bone diseases where bone loss is a major concern. These compounds are also characterized by high cell differentiation activity.

Claims

1. A method of treating skin conditions selected from the group consisting of dermatitis, eczema, keratosis, lack of skin firmness, wrinkles, lack of dermal hydration and insufficient sebum secretion which comprises administering to a subject an effective amount of a compound selected from the group consisting of:

19-nor-2α

-ethyl-1α

,25-dihydroxyvitamin D3,

19-nor-2β

-ethyl-1α

,25-dihydroxyvitamin D3,

19-nor-20(S)-2α

-ethyl-1α

,25-dihydroxyvitamin D3,

19-nor-20(S)-2β

-ethyl-1α

,25-dihydroxyvitamin D3,

19-nor-2(E)-ethylidene-1α

,25-dihydroxyvitamin D3,

19-nor-2(Z)-ethylidene-1α

,25-dihydroxyvitamin D3,

19-nor-2(E)-ethylidene-20(S)-1α

,25-dihydroxyvitamin D3, and

19-nor-2(Z)-ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃.

2. The method of claim 1 wherein said effective amount comprises about 0.1 μ

g/day to about 100 μ

g/day of said compound.

3. The method of claim 1 wherein the compound is 19-nor-2α

-ethyl-1α

,25-dihydroxyvitamin D₃.

4. The method of claim 1 wherein the compound is 19-nor-2β

-ethyl-1α

,25-dihydroxyvitamin D₃.

5. The method of claim 1 wherein the compound is 19-nor-20(S)-2α

-ethyl-1α

,25-dihydroxyvitamin D₃.

6. The method of claim 1 wherein the compound is 19-nor-20(S)-2β

-ethyl-1α

,25-dihydroxyvitamin D₃.

7. The method of claim 1 wherein the compound is 19-nor-2(E)-ethylidene-1α

,25-dihydroxyvitamin D₃.

8. The method of claim 1 wherein the compound is 19-nor-2(Z)-ethylidene-1α

,25-dihydroxyvitamin D₃.

9. The method of claim 1 wherein the compound is 19-nor-2(E)-ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃.

10. The method of claim 1 wherein the compound is 19-nor-2(Z)-ethylidene-20(S)-1α

,25-dihydroxyvitamin D₃.

11. The method of claim 1 wherein the compound is administered orally.

12. The method of claim 1 wherein the compound is administered parenterally.

13. The method of claim 1 wherein the compound is administered transdermally.

14. The method of claim 1 wherein the compound is administered topically.

15. The method of claim 1 wherein the compound is administered in a dosage of from about 0.01 μ

g to about 100 μ

g per day.

16. The method of claim 1 wherein the compound is administered in a dosage of from about 0.1 μ

g to about 50 μ

g per day.