Des-C,D analogs of 1α,25-dihydroxy-19-norvitamin D3

• US 7,534,777 B2
• Filed: 08/30/2006
• Issued: 05/19/2009
• Est. Priority Date: 08/30/2005
• 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: Sicinski, Rafal, Plum, Lori A., DeLuca, Hector F., Clagett-Dame, Margaret, Grzywacz, Pawel, Plonska-Ocypa, Katarzyna
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US11/512,705
• Publication Number:
  US 20070112077A1
• Time in Patent Office: 993 Days
• Field of Search: 514/167, 552/653
• US Class Current: 514/167
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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 5/18 of the parathyroid hormones
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 35/17 with unsaturation only outside the ring
• 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: C07C 403/08 by hydroxy groups
• CPC Class Codes: C07C 45/292 with chromium derivatives
• CPC Class Codes: C07C 45/30 with halogen containing compounds, e.g. hypohalogenation
• CPC Class Codes: C07C 47/19 containing hydroxy groups sugars C07H
• 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

Des-C,D 2-methylene-19-norvitamin D₃ analogs are provided including compounds of formula 1, in which R¹ is a straight or branched chain alkyl or alkylene group having from 8 to 27 carbons and bearing an OY³ group; and Y¹, Y² and Y³ 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 of formula 1:

2. The compound of claim 1, wherein the compound has the formula 1A, 1B, or 1C

3. The compound of claim 2, wherein Y¹, Y², and Y³ are all H and the compound has the formula 1A1, 1B1, or 1C1

4. The compound of claim 2, wherein the compound has the formula 1A2, 1B2, or 1C2

5. The compound of claim 2, wherein X¹, X², X³, and X⁴ are independently selected from H or methyl groups.

6. The compound of claim 5, wherein X¹, X², X³, and X⁴ are all H.

7. The compound of claim 2, wherein the compound has the formula 1C3

8. The compound of claim 1, wherein Y¹ and Y² are both hydroxy protecting groups.

9. The compound of claim 8, wherein Y¹ and Y² are both t-butyldimethylsilyl groups.

10. The compound of claim 1, wherein Y³ is a trialkylsilyl group.

11. The compound of claim 10, wherein Y³ is a triethylsilyl group.

12. The compound of claim 2, wherein the compound has the formula 1C4

13. A pharmaceutical formulation, comprising:

the compound of claim 1 and a pharmaceutically acceptable carrier.

14. The pharmaceutical formulation of claim 13, wherein the amount of the compound in the pharmaceutical formulation ranges from about 0.01 μ

g to about 1 mg per gram of the pharmaceutical formulation.

15. The pharmaceutical formulation of claim 13, wherein the amount of the compound in the pharmaceutical formulation ranges from about 0.1 μ

g to about 500 μ

g per gram of the pharmaceutical formulation.

16. A method of treating a subject suffering from a biological disorder, comprising administering an effective amount of the compound of claim 1, 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, eczema, or inflammatory bowel diseases;

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

or secondary hyperparathyroidism.

17. The method of claim 16, wherein the compound is administered orally, parenterally, rectally, transdermally, or topically to the subject.

18. The method of claim 16, wherein the compound is administered by delivering the compound in an aerosol.