19,26,27-TRINOR-1alpha,25-DIHYDROXYVITAMIN D3 COMPOUNDS

• US 20070219168A1
• Filed: 05/31/2007
• Published: 09/20/2007
• Est. Priority Date: 05/03/2005
• Status: Active Grant

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Plum, Lori, Clagett-Dame, Margaret, Grzywacz, Pawel, DeLuca, Hector
• Granted Patent: US 8,030,295 B2
• Time in Patent Office: Days
• US Class Current: 514/167
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• 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 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• 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: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Compounds of formula 1 are provided where X¹, X², and X³ are independently selected from H or hydroxy protecting groups, and R¹ and R² have the definitions provided herein. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.

Claims

1. A method of treating a subject suffering from a biological disorder, comprising administering an effective amount of a compound or a composition comprising an effective amount of the compound and a pharmaceutical carrier to the subject, wherein the biological disorder is selected from renal osteodystrophy, secondary hyperparathyroidism, psoriasis, type I diabetes, lupus, rheumatoid arthritis, or a cancer selected from leukemia, colon cancer, breast cancer, or prostate cancer, and the compound has the formula 1,

wherein,

X¹, X², and X³ are independently selected from H or hydroxy protecting groups;

and

R¹ and R² are independently selected from H or straight or branched chain alkyl groups having from 1 to 8 carbon atoms;

or R¹ and R² join together to form a group of formula 2

where the wavy line indicates the point of attachment to the carbon at the 2 position of the vitamin D analog, and R³ and R⁴ are independently selected from H or straight or branched chain alkyl groups having from 1 to 8 carbon atoms.

2. The method of claim 1, wherein the biological disorder is hypercalcemia, asthma, or eczema.

3. The method of claim 1, wherein the compound or composition is administered orally, parenterally, rectally, transdermally, or topically to the subject.

4. The method of claim 1, wherein the compound or composition is administered by delivering the compound or composition in an aerosol.

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

g per day to 1 mg per day.

6. The method of claim 1, wherein X¹, X², and X³ are all H.

7. The method of claim 6, wherein the biological disorder is hypercalcemia, asthma, or eczema.

8. The method of claim 6, wherein the compound or composition is administered orally, parenterally, rectally, transdermally, or topically to the subject.

9. The method of claim 6, wherein the compound or composition is administered by delivering the compound or composition in an aerosol.

10. The method of claim 6, wherein the compound is administered in a dosage of from 0.01 μ

g per day to 1 mg per day.

11. The method of claim 1, wherein the compound has the formula 3A,

or 3B,

or 3C,

12. The method of claim 11, wherein the biological disorder is hypercalcemia, asthma, or eczema.

13. The method of claim 11, wherein the compound or composition is administered orally, parenterally, rectally, transdermally, or topically to the subject.

14. The method of claim 11, wherein the compound or composition is administered by delivering the compound or composition in an aerosol.

15. The method of claim 11, wherein the compound or composition is administered in a dosage of from 0.01 μ

g per day to 1 mg per day.