(E)-20(22)-dehydrovitamin D compounds

• US 5,484,781 A
• Filed: 05/16/1995
• Issued: 01/16/1996
• Est. Priority Date: 11/03/1993
• 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., Sicinski, Rafal R.
• Primary Examiner(s): Kestler, Kimberly J.
• Application Number:
  US08/442,463
• Time in Patent Office: 245 Days
• Field of Search: 552/653, 514/167
• US Class Current: 514/167
• 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: C07J 71/0042 Nitrogen only

Abstract

Vitamin D₃ analogs in which a double bond has been introduced into the side chain between carbons 20 and 22. The compounds are characterized by a marked intestinal calcium transport activity while exhibiting much lower activity than 1α,25-dihydroxyvitamin D₃ in their ability to mobilize calcium from bone. Because of their preferential calcemic activity, these compounds would be useful for the treatment of diseases where bone formation is desired, such as osteoporosis. The compounds also have relatively high HL-60 cell differentiation activity making them useful for the treatment of diseases characterized by abnormal cell differentiation or cell proliferation, such as psoriasis.

Claims

1. A method of treating psoriasis which comprises administering to a patient an effective amount of a compound having the formula ##STR11## where Y¹ is hydrogen or a hydroxy-protecting group, R¹ represents hydrogen, hydroxy or protected hydroxy, and where R is hydrogen, aryl, alkyl, hydroxyalkyl or fluoroalkyl group, or R may represent the following side chain fragment:

##STR12## wherein R¹ is as defined above, R² and R³ are each selected from the group consisting of alkyl, hydroxyalkyl and fluoroalkyl, or, when taken together represent the group --(CH₂)_m -- where m is an integer having a value of from 2 to 5, R⁴ is selected from the group consisting of hydrogen, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, R⁵ is selected from the group consisting of hydrogen, fluorine, alkyl, hydroxyalkyl and fluoroalkyl, and wherein n is an integer having a value of from 1 to 5.

2. The method of claim 1 where the compound is administered topically.

3. The method of claim 1 where the compound is administered in a dosage of from 0.5 μ

g to 50 μ

g per day.