21-norvitamin D compounds

• US 5,384,313 A
• Filed: 11/24/1993
• Issued: 01/24/1995
• Est. Priority Date: 11/24/1993
• 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., Wicha, Jerzy
• Primary Examiner(s): Richter, Johann
• Assistant Examiner(s): PRIOR, KIMBERLY
• Application Number:
  US08/157,888
• Time in Patent Office: 426 Days
• Field of Search: 552/653, 514/167
• US Class Current: 514/167
• 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 13/007 with double bond in position 17 (20)
• CPC Class Codes: C07J 31/006 not covered by C07J31/003
• CPC Class Codes: C07J 53/004 3 membered carbocyclic rings
• CPC Class Codes: C07J 9/00 Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane

Abstract

21-norvitamin D₃ analogs in which the methyl group normally attached to the side chain at carbon 20 has been replaced by a hydrogen atom. 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 are useful for the treatment of diseases where bone formation is desired, such as osteodystrophy. Novel intermediates formed during the synthesis of the end products are also disclosed.

Claims

1. A compound having the formula ##STR7## where X₆ may be hydrogen or a hydroxy-protecting group, and Z is selected from the group consisting of Y, --OY, --CH₂ OY, --C═

CY and --C═

CHY, where the double bond may have the cis or trans stereochemical configuration, and where Y is selected from the group consisting of hydrogen, methyl, --CR⁵ O and a radical of the structure, ##STR8## where m and n independently represent integers from 0 to 5, where R¹ is selected from the group consisting of hydrogen, hydroxy, protected-hydroxy, fluoro, trifluoromethyl, and C_1-5 alkyl, which may be straight-chain or branched and optionally bear a hydroxy or protected-hydroxy substituent, and where each of R², R³, and R⁴ independently is selected from the group consisting of hydrogen, fluoro, trifluoromethyl, and C_1-5 alkyl, which may be straight-chain or branched and optionally bear a hydroxy or protected-hydroxy substituent, and where R¹ and R², taken together, represent an oxo group, or an alkylidene group, ═

CR² R³ or the group --(CH₂)p--, where p is an integer from 2 to 5, and where R³ and R⁴, taken together, represent an oxo group, or the group --(CH₂)q, where q is an integer from 2 to 5, and where R⁵ represents hydrogen, hydroxy, protected hydroxy, or C_1-5 alkyl.

2. The compound of claim 1 where Z is CH₂ CH₂ CH₂ C(CH₃)₂ OH and X₆ is hydrogen.

3. A pharmaceutical composition containing at least one compound as claimed in claim 1 together with a pharmaceutically acceptable excipient.

4. The pharmaceutical composition of claim 3 containing 21-nor-1α

,25-dihydroxyvitamin D₃ in an amount from about 0.5 μ

g to about 50 μ

g.

5. A compound having the formula ##STR9## where X₄ and X₅, which may be the same or different are hydrogen, hydroxy, or taken together to form an oxo group, and Z is as defined in claim 1.