2-methylene-19-nor-(23S)-25-dehydro-1α-hydroxyvitamin D3-26,23-lactone and 2-methylene-19-nor-(23R)-25-dehydro-1α-hydroxyvitamin D3-26,23-lactone

• US 7,541,349 B2
• Filed: 06/22/2007
• Issued: 06/02/2009
• Est. Priority Date: 03/29/2005
• 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 A., DeLuca, Hector F., Clagett-Dame, Margaret, Grzywacz, Pawel, Chiellini, Grazia
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US11/767,085
• Publication Number:
  US 20070259953A1
• Time in Patent Office: 711 Days
• Field of Search: 514/167, 552/653
• US Class Current: 514/167
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• 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 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 1A and 1B are provided where X¹ and X² 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 disorders.

Claims

1. A method of treating a subject suffering from a biological disorder selected from the group consisting of asthma and eczema, comprising administering an effective amount of a compound of formula 1A1 or 1B1, a mixture thereof, or a pharmaceutical formulation comprising the compound or mixture of compounds and a pharmaceutically acceptable carrier to the subject,

2. The method of claim 1, wherein the compound or mixture of compounds antagonizes a vitamin D receptor in the subject after administration.

3. The method of claim 1, wherein the biological disorder is asthma.

4. The method of claim 1, wherein the biological disorder is eczema.

5. The method of claim 1, wherein the compound, the mixture of compounds, or the pharmaceutical formulation is administered orally, parenterally, rectally, transdermally, or topically to the subject.

6. The method of claim 1, wherein the compound, the mixture of compounds, or the pharmaceutical formulation is administered by delivering the compound, mixture of compounds or pharmaceutical formulation in an aerosol.

7. The method of claim 1, wherein the compound or the mixture of compounds is administered in a dosage of from 0.01 μ

g per day to 1 mg per day.

8. The method of claim 1, wherein the compound has the formula 1A2 or 1B2,

9. The method of claim 1, wherein the subject is human.

10. A method of treating hypercalcemia, sarcoidosis, or vitamin D intoxication in an animal subject suffering from hypercalcemia, sarcoidosis, or vitamin D intoxication, comprising administering a compound of formula 1A1 or 1B1, a mixture thereof, or a pharmaceutical formulation comprising the compound or mixture of compounds and a pharmaceutically acceptable carrier to the animal subject,

11. The method of claim 10, wherein the compound, the mixture of compounds, or the pharmaceutical formulation is administered using an inhaler or nebulizer.

12. The method of claim 10, wherein the compound is administered orally, parenterally, rectally, transdermally, or topically to the subject.

13. The method of claim 10, wherein the compound has the formula 1A2 or 1B2,

14. The method of claim 10, wherein the animal subject is human.