Diastereomers of 2-methylene-19-nor-22-methyl-1α,25-dihydroxyvitamin D 3

• US 8,664,206 B2
• Filed: 01/06/2012
• Issued: 03/04/2014
• Est. Priority Date: 03/23/2010
• Status: Active Grant

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: DeLuca, Hector F., Flores, Agnieszka, Grzywacz, Pawel, Plum, Lori A., Clagett-Dame, Margaret, Thoden, James B., Holden, Hazel M.
• Primary Examiner(s): Badio, Barbara P
• Application Number:
  US13/344,987
• Publication Number:
  US 20120165300A1
• Time in Patent Office: 788 Days
• Field of Search: 514/167, 552/653, 568/819
• US Class Current: 514/167
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• 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 35/00 Antineoplastic agents
• 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: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2602/24 the ring system containing nine carbon atoms, e.g. perhydroindane
• 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
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Compounds of formula I are provided where X¹, X², and X³ are independently selected from H or hydroxy protecting groups. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.

Claims

1. A compound according to formula I

2. The compound of claim 1, wherein X¹, X², and X³ are hydroxy protecting groups.

3. The compound of claim 2, wherein X¹ and X² are both t-butyldimethylsilyl groups and X³ is a triethylsilyl group.

4. A compound according to formula II

5. The compound of claim 4, according to formula IIA

6. The compound of claim 4, according to formula IIB

7. The compound of claim 4, according to formula IIC

8. The compound of claim 4, according to formula IID

9. The compound of claim 4, according to formula IIE, IIF, IIG, or IIH

10. The compound of claim 4, according to formula IIG or IIH

11. A pharmaceutical composition, comprising an effective amount of the compound of claim 4 and a pharmaceutically acceptable carrier.

12. A method of treating a subject suffering from a biological condition, comprising administering an effective amount of the compound of claim 4 to the subject, wherein the biological condition is selected from psoriasis;

leukemia;

colon cancer;

breast cancer;

prostate cancer;

multiple sclerosis;

lupus;

diabetes mellitus;

host versus graft reaction;

rejection of organ transplants;

an inflammatory disease selected from rheumatoid arthritis, asthma, or inflammatory bowel diseases;

a skin condition selected from wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration, or insufficient sebum secretion;

renal osteodystrophy;

or osteoporosis.

13. The method of claim 12, wherein the biological condition is psoriasis.

14. The method of claim 12, wherein the biological condition is selected from leukemia, colon cancer, breast cancer, or prostate cancer.

15. The method of claim 12, wherein the biological condition is selected from multiple sclerosis, lupus, diabetes mellitus, host versus graft reaction, or rejection of organ transplants.

16. The method of claim 12, wherein the biological condition is selected from rheumatoid arthritis, asthma, or inflammatory bowel diseases selected from celiac disease, ulcerative colitis and Crohn'"'"'s disease.

17. The method of claim 12, wherein the biological condition is selected from wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration, or insufficient sebum secretion.

18. The method of claim 12, wherein the compound is administered in a dosage of from 0.01 μ

g per day to 1 mg per day.

19. A compound according to Formula IIIC or IIID, wherein X³ is H:

20. The compound of claim 19, wherein the compound is in crystalline form.

21. The crystalline compound of claim 20 wherein the compound is of Formula IIIC and has a molecular packing arrangement defined by monoclinic space group C2 and unit cell dimensions a=26.4 Å

, α

=90°

, b=6.08 Å

, β

=118°

, c=12.7 Å

, γ

=90°

.

22. The crystalline compound of claim 20 wherein the compound is of Formula IIID and has a molecular packing arrangement defined by monoclinic space group P2 and unit cell dimensions a=11.4 Å

, α

=90°

, b=16.5 Å

, β

=119°

, c=11.5 Å

, γ

=90°

.