Homologated vitamin D.sub.2 compounds and the corresponding 1.alpha.-hydroxylated derivatives

• US 5,414,098 A
• Filed: 12/03/1992
• Issued: 05/09/1995
• Est. Priority Date: 02/14/1990
• 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., Schnoes, Heinrich K., Perlman, Kato L.
• Primary Examiner(s): Richter, Johann
• Assistant Examiner(s): Kestler, Kimberly J.
• Application Number:
  US07/985,432
• Time in Patent Office: 887 Days
• Field of Search: 552/653, 514/167
• US Class Current: 552/653
• 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: C07J 71/0042 Nitrogen only

Abstract

The invention provides new 24, 26, and/or 27 homologated vitamin D₂ compounds, such as 26,27-dihomo-1α-hydroxyvitamin D₂, 26,27-dihomo-1α-hydroxy-24-epi-vitamin D₂, 26,27-dihomo-1α,25-dihydroxy-24-epi-vitamin D₂ and certain hydroxy-protected derivatives thereof. The new epi compounds in particular exhibit a distinctive activity pattern comprising high potency in stimulating intestinal calcium transport and little or no activity in inducing bone calcium mobilization or the differentiation of undifferentiated cells in culture, thereby evincing utility in the treatment of diseases characterized by loss of bone mass. In contrast, the natural form exhibits no activity in either mobilizing calcium from bone or stimulating intestinal calcium transport. A process for preparing such compounds is also disclosed.

Claims

1. Vitamin D compounds having the formula:

where the configuration about carbon 24 may be R or S and wherein n is an integer having a value of 3, X₁ is selected from hydrogen or a hydroxy protecting group, X₂ is selected from hydrogen, hydroxy and protected hydroxy, X₃ is selected from hydrogen, hydroxy, and protected hydroxy, each R₃ is independently selected from alkyl, hydroxy, protected hydroxy, hydrogen or fluorine, with the proviso that at least one R₃ must be alkyl, and wherein R₁ and R₂, which may be the same or different, are each selected from an alkyl or aryl group.

2. The compounds of claim 1 wherein X₁ and X₂ are both hydrogen, and X₃ is hydroxy.

3. The compounds of claim 1 wherein X₁ and X₃ are both hydrogen, and X₂ is hydroxy.

4. The compounds of claim 1 wherein X₁ is hydrogen, and X₂ and X₃ are both hydroxy.

5. 1α

,25-dihydroxy-[22E-dehydro-]24-dihomo-vitamin D₂ where the configuration about carbon 24 may De R or 5 having the formula;

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